NDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.

UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury. Three-month-old male Ndrg2+/+ and Ndrg2-/- mice (16-18g) were exposed to UVB to induce acute skin damage, and then dorsal skin samples were collected for subsequent analyses. UVB-induced skin damage was scored. Western Blot Analysis, immunofluorescence (IF) double labeling, and immunohistochemistry (IHC) were employed to assess NDRG2 expression and/or distribution. The concentrations of TNF-α, IL-6, IL-1ß, MPO, MMP8, superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining were employed to determine pathological changes. RNA sequencing and analysis were performed to estimate transcript expression levels and analyze mRNA expression. DESeq2 software was employed to identify differentially expressed genes (DEGs). DEGs were visualized using volcanic and heat maps. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to identify primary biological functions, metabolic pathways, or signal transduction pathways associated with DEGs. UVB-challenged Ndrg2-/- mice exhibited significantly exacerbated skin damage (erythema, edema, and erosion), neutrophil infiltration, and apoptosis compared to Ndrg2+/+ mice. Furthermore, UVB-challenged Ndrg2-/- mice displayed significantly elevated pro-inflammatory cytokines, myeloperoxidase (MPO), matrix metalloproteinase-8 (MMP8), and reduced antioxidant expression. RNA sequencing identified 1091 significantly differentially expressed genes enriched in inflammation, immune response, and oxidative stress pathways. In conclusion, the deficiency of Ndrg2 markedly exacerbated UVB-induced skin damage by promoting inflammatory responses and inhibiting antioxidant responses. This suggests that stabilizing NDRG2 expression holds promise as a therapeutic strategy for protecting against UVB-induced skin damage.

Super-Selective Intra-arterial Thrombolytic Therapy for Peripheral Facial Paralysis After Postauricular Hyaluronic Acid Injection for the Esthetic Correction of Lying Ears.

BACKGROUND: Hyaluronic acid (HA) injection in the auricular base is one of the most popular and non-surgical cosmetic procedures for correcting lying ears and optimizing the facial profile because of its minimal invasiveness, immediate effect and safety (Li et al. in Aesthet Surg J 44: 746-75, 2024). But we have recently discovered that this treatment may lead to a new and rare complication called peripheral facial paralysis that has never been reported before. Until now, the etiology, clinical traits, treatment strategies, outcomes and possible reversibility have not been characterized. METHODS: In the present study, we enrolled 4 patients with peripheral facial paralysis after subcutaneous postauricular HA filler injection. Preoperative digital subtraction angiography revealed a vascular embolism. Then, the patients underwent super-selective facial arterial thrombolytic therapy via hyaluronidase and papaverine injections. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: The patients were relieved of their clinical symptoms and the significant improvement was observed in terms of motor function in her left facial areas after treatment. The auricular skin necrosis of all patients was restored to near normal appearance. CONCLUSION: Our results indicate that super-selective facial arterial thrombolytic therapy is feasible for patients with peripheral facial paralysis induced by HA embolism. It was also beneficial in the recovery from skin necrosis. The therapy was shown to be worthy of clinical application. 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 .

Efficacy of Superselective Intra-arterial Recanalization of Embolized Arteries Resulting from Facial Hyaluronic Acid Injection.

BACKGROUND: Arterial embolism is a rare complication caused by hyaluronic acid (HA) injection. However, it is one of the most serious complications. Once it happens, the complication would have a great and long-term impact on patients. Intra-arterial recanalization has been reported for recovering the visual acuity in patients with visual loss caused by hyaluronic acid. There is little report about the benefits of superselective intra-arterial recanalization therapy for skin wounds caused by hyaluronic acid vascular embolization. METHODS: Eight patients who had received the superselective intra-arterial recanalization therapy were retrospectively reviewed. Hyaluronidase was injected into the facial artery by superselective intra-arterial recanalization therapy, followed by symptomatic treatment. The facial artery recanalization was successfully performed and no interventional procedure-related adverse events happened. RESULTS: Arterial embolization accompanies by the interruption or reduction of blood supply, followed by ochrodermia, pain, numbness, swelling, yellowish white secreta and even necrosis on skin wound area. Early detection of skin blood supply disorders and early recovery of blood supply are very critical to treat facial artery embolization caused by HA. After superselective intra-arterial recanalization therapy, the blood supply to facial skin was restored and skin wounds recovered in all patients. Only 1 patient was left with small and superficial scars. CONCLUSION: Superselective intra-arterial recanalization therapy is an effective and safe method that can alleviate skin wounds caused by HA vascular embolization. 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 .

Efficacy of Fractional Micro-plasma Radio Frequency Technology in Treating Hypertrophic Burn Scars in Asian Patients Under General Anesthesia: A Retrospective Study of 104 Cases.

BACKGROUND: Laser and other energy devices have been widely used in the minimally invasive treatment of scars. Among various technologies, Fractional Micro-Plasma Radio Frequency Technology (FMRT) has gained extensive consensus in the treatment of various types of scars and skin disorders, such as wrinkles, skin laxity, and pigmentation. OBJECTIVE: This study is a retrospective clinical trial aimed at assessing the effectiveness and safety of FMRT for hypertrophic burn scars treatment in the Asian population under different anesthesia methods. METHODS: A total of 104 patients with hypertrophic burn scars treated in our department from May 2018 to May 2022 were selected. Scar assessment scales were applied to observe changes in scars before and after FMRT treatment. RESULTS: A prospective study of 104 patients found that female patients were more likely to undergo laser treatment under general anesthesia (P < 0.05). Postoperative VSS total score, VSS total score difference, and immediate postoperative pain score were all better with general anesthesia compared to local anesthesia (P < 0.05). There were more significant improvements in scar color, vascular distribution, and flexibility (P < 0.05). When comparing the treatment outcomes between females and males, it was found that general anesthesia patients were superior to local anesthesia patients in terms of color score, vascular distribution score, flexibility score, and postoperative VSS total score 6 months after the final treatment. General anesthesia patients had a shorter hospital stay. Overall treatment evaluation was better for female general anesthesia patients than male patients. CONCLUSION: General anesthesia combined with FMRT is an effective, safe, and more acceptable treatment method for hypertrophic burn scars in the Asian population. BULLET POINTS: In the Asian population, the combined use of general anesthesia and Fractional Micro-Plasma Radio Frequency Technology (FMRT) is an effective, safe, and accepted method for treating skin scars. LEVEL OF EVIDENCE II: 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 .

A case of IgG4-related ophthalmic disease after SARS-CoV-2 vaccination: case report and literature review.

Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting the world with a surge in cases. A variety of autoimmune diseases occur after SARS-CoV-2 infection or vaccination, of which IgG4-related disease (IgG4-RD) is an important type. IgG4-RD can involve multiple organs of the body. The ocular manifestation of IgG4-RD is called IgG4-related ophthalmic disease (IgG4-ROD). We herein report a patient diagnosed with IgG4-ROD. The patient developed ptosis and vision loss after SARS-CoV-2 vaccination, and the symptoms worsened after SARS-CoV-2 infection. After excluding other diseases like myasthenia gravis and Eaton-Lambert syndrome that may cause ptosis, the diagnosis of IgG4-ROD was confirmed by pathological examination. We discussed the predisposing factors, diagnosis and treatment of this patient to provide a more empirical and theoretical basis for clinical diagnosis and treatment. We conducted a literature review of previously reported cases of IgG4-RD following SARS-CoV-2 infection or vaccination. We retrieved a total of 9 cases, of which 5 developed symptoms after vaccination and 4 after infection. Demographic and clinical characteristics were summarized. In conclusion, our case represents the first case of proven IgG4-ROD after COVID-19 vaccination. We believe that IgG4-ROD and SARS-CoV-2 infection or vaccination are closely related, and the immune system disorder caused by SARS-CoV-2 infection or vaccination may be a key factor in the pathogenesis of IgG4-RD. But for now, there is no direct evidence that there is a causal relationship between SARS-CoV-2 infection or vaccination and IgG4-ROD, which still needs more research and exploration to confirm.

Envoplakin Inhibits Macrophage Polarization by Altering the Inflammatory Tumor Microenvironment of Melanoma Through the RAS / ERK Signaling Pathway.

Purpose: Tumor growth induces the tumor margin to become a transition zone rich in immune cells. EVPL is a potential prognostic biomarker for melanoma. Melanoma is difficult to cure because of its high metastasis, so it is urgent to find effective genes to inhibit tumor progression and regulate tumor microenvironment. Methods: Firstly, differentially expressed genes (DEGs) among normal skin, nevus and melanoma samples in GSE3189 were screened. Bioinformatics was used to further explore the hub genes and enriched pathways closely related to the inflammatory response of DEGs in melanoma. We selected EVPL, which is associated with the Ras/Raf signaling pathway, for in vitro study. CCK-8, colony formation, wound healing, Transwell and flow cytometry assays were respectively used to evaluate the proliferation, migration, invasion, and apoptosis of cancer cells. Enzyme-linked immunosorbent assay was conducted for the monitoring of changes in the tumor microenvironment. To evaluate the effect of EVPL on macrophage recruitment, we established a co-culture system in a Transwell chamber. The polarization of macrophages was examined after treatment of cells with RAS/ERK signaling inhibitors SCH772984 and sh-EVPL. Additionally, changes in the expression of pathway proteins were measured by Western blot. Results: Among the screened hub genes, EVPL was associated with the Ras/Raf pathway, a key signaling pathway in melanoma, and may be involved in regulating the inflammatory microenvironment of melanoma. Oe-EVPL was proved to suppress melanoma cell malignant progression. By inhibiting EVPL expression, the inhibitory effects on melanoma progression induced by the addition of SCH772984 were reversed. Furthermore, EVPL was found to inhibit the expression of chemokines, the recruitment of macrophages, and the polarization of macrophages through the Ras/Raf/ERK signaling pathway. Conclusion: EVPL can inhibit the progression of melanoma through the RAS/ERK signaling pathway, change the inflammatory tumor microenvironment of melanoma, and inhibit the recruitment of macrophages.

Superselective Arterial Hyaluronidase Thrombolysis is an Effective Treatment for Hyaluronic Acid-Induced Retinal Artery Occlusion: Study in a Rabbit Model.

BACKGROUND: There are serious complications associated with hyaluronic acid (HA) facial injections, including vision impairment due to retinal artery ischemia. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in rabbit. We used this to verify the efficacy of hyaluronidase intra-artery thrombolysis in the treatment of hyaluronic acid-induced retinal artery occlusion. METHODS: Retinal artery ischemia was induced by injecting HA into the ophthalmic artery (OA) of adult chinchilla rabbit, and reperfusion was achieved by intra-artery thrombolysis therapy with hyaluronidase following 60 min and 4 h of occlusion. Digital subtraction angiography (DSA) and fundus fluorescein angiography (FFA) were used to evaluate blood flow in the retina. Electroretinogram (ERG), hematoxylin and eosin staining and transmission electron microscope were used to evaluate the structure and function of the retina after ischemia and reperfusion following 60 min and 4 h of occlusion. RESULTS: DSA and FFA images confirmed occlusion of the ophthalmic and central retinal arteries, as well as reperfusion after hyaluronidase thrombolysis. ERG indicated retinal dysfunction following ischemia, and thrombolysis partially rescued its impairment following 4 h of occlusion. Hematoxylin and eosin staining and TUNEL staining revealed ischemia-induced histological damages in the retina at different time windows, and hyaluronidase thrombolysis partially mitigated these damages. CONCLUSIONS: We report a method to establish a HA-induced retinal artery occlusion animal model. Hyaluronidase intra-artery thrombolysis was used to recanalize the embolized OA at different time points. Using our method, we achieved retinal reperfusion, and an improvement was observed in the visual function of rabbits after hyaluronidase thrombolysis following 4 h of occlusion. We believe that hyaluronidase intra-artery thrombolysis is an effective method to treat HA-induced retinal artery occlusion in clinic. LEVEL OF EVIDENCE II: 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 .

Exploring Superselective Intraarterial Thrombolysis for Autologous Fat Injection-Induced Vision Loss.

BACKGROUND: Intravascular injection represents the most severe complication in fat transplantation procedures. Currently, the prognosis for patients who suffer from blindness due to fat transplantation-induced ocular vascular occlusion is far from optimistic. OBJECTIVES: The aim of this study was to explore and evaluate the efficacy and safety of arterial thrombolysis in the treatment of ocular vascular occlusion caused by fat transplantation. METHODS: We analyzed the data of 12 patients who underwent intraarterial thrombolysis and conservative treatments for facial autologous fat grafting-associated ocular vascular occlusion. Among the cases, there were 6 instances of ophthalmic artery embolism and 6 cases of central retinal artery occlusion. All patients suffered with sudden blindness, sometimes accompanied by eye pain, ptosis, strabismus, skin necrosis at the injection site, or cerebral microinfarction. They received symptomatic conservative treatments and intraarterial thrombolysis, encompassing mechanical vessel recanalization, vessel dilation, and dissolution of thrombus constituents. RESULTS: Following intraarterial thrombolysis, a noteworthy improvement in the blood flow of both the main trunk and peripheral branches of the ophthalmic artery was observed in the majority of patients when contrasted with their pretreatment status. One patient experienced a headache intraoperatively, while no significant discomfort was reported by the remaining patients. After conservative treatments and intraarterial thrombolysis, all patients experienced improvement in ocular symptoms, skin necrosis, and cerebral infarction. Three patients demonstrated improvement in visual acuity. These patients had surpassed the recommended time window for treatment, yet the occlusion of the ophthalmic artery was not complete. CONCLUSIONS: Intraarterial thrombolysis combined with conservative treatments achieves early perfusion and is expected to promote visual recovery. Hospitals that possess the necessary treatment capabilities are encouraged to establish this therapeutic pathway.

Impact of SARS-CoV-2 Vaccination or Infection on the Safety and Efficacy of Aesthetic Injections: A Systematic Review.

BACKGROUND: Aesthetic injections have become increasingly popular for maintaining a youthful appearance. However, with the rise of SARS-CoV-2, there have been concerns about potential complications. This study aims to summarize and understand the complications that occur in individuals who have received cosmetic injections after SARS-CoV-2 infection or vaccination. By doing so, we hope to provide recommendations to minimize these complications and ensure the safety of aesthetic treatments in the current COVID-19 era. METHODS: The PRISMA guidelines, the Preferred Reporting Program for Systematic Reviews and Meta-Analyses, were used for this review. Databases including PubMed, EMBASE, Medline, Web of Science and ScienceDirect were searched. The last search time of each database was May 10, 2023. In addition, relevant references were manually searched. RESULTS: A total of 26 studies containing 139 patients were searched. The complication with the highest percentage of reported patients was delayed inflammatory response (DIR) (n = 68; 48.92%), followed by diminished efficacy (n = 45; 32.37%) and filler reaction (n = 12; 8.63%). The remaining complications include hypersensitivity reactions, symptomatic hypercalcemia, sub-acute hypersensitive reactions, hyperalgesia, infection, fat necrosis and granulomatous reaction. CONCLUSIONS: Cosmetic injectable procedures are generally safe but may have adverse effects, particularly during the pandemic. It is important for individuals to fully understand these risks beforehand. Clinicians should be knowledgeable about adverse event mechanisms and management to prevent issues. Industry leaders should strengthen risk management efforts to ensure safe and steady development of cosmetic injections. Overall, a comprehensive understanding, effective communication and risk management are crucial for the safe use of cosmetic injectable procedures. LEVEL OF EVIDENCE III: 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 at www.springer.com/00266 .

Identification and validation of CRLF1 and NRG1 as immune-related signatures in hypertrophic scar.

BACKGROUND: Hypertrophic scar (HTS) is a prevalent chronic inflammatory skin disorder characterized by abnormal proliferation and extracellular matrix deposition and the precise mechanisms underlying HTS remain elusive. This study aimed to identify and validate potential immune-related genes associated with hypertrophic scar formation. METHODS: Skin samples from normal (n = 12) and hypertrophic scar tissues (n = 12) were subjected to RNA-seq analysis. Differentially expressed genes (DEGs) and significant modular genes in Weighted gene Co-expression Network Analysis (WGCNA) were identified. Subsequently, functional enrichment analysis was performed on the intersecting genes. Additionally, eight immune-related genes were matched from the ImmPort database. Validation of NRG1 and CRLF1 was carried out using an external cohort (GSE136906). Furthermore, the association between these two genes and immune cells was assessed by Spearman correlation analysis. Finally, RNA was extracted from normal and hypertrophic scar samples, and RT-qPCR, Immunohistochemistry staining and Western Blot were employed to validate the expression of characteristic genes. RESULTS: A total of 940 DEGs were identified between HTS and normal samples, and 288 key module genes were uncovered via WGCNA. Enrichment analysis in key module revealed involvement in many immune-related pathways, such as Th17 cell differentiation, antigen processing and presentation and B cell receptor signaling pathway. The eight immune-related genes (IFI30, NR2F2, NRG1, ESM1, NFATC2, CRLF1, COLEC12 and IL6) were identified by matching from the ImmPort database. Notably, we observed that activated mast cell positively correlated with CRLF1 expression, while CD8 T cells exhibited a positive correlation with NRG1. The expression of NRG1 and CRLF1 was further validated in clinical samples. CONCLUSION: In this study, two key immune-related genes (CRLF1 and NRG1) were identified as characteristic genes associated with HTS. These findings provide valuable insights into the immune-related mechanisms underlying hypertrophic scar formation.

The Comparison of Efficacy and Safety Between General and Topical Anesthesia on Micro-Plasma Radiofrequency Treatment for Hypertrophic Scar: A Retrospective Cohort Study.

BACKGROUND: While micro-plasma radiofrequency (MPR) treatment has a significant impact on hypertrophic scars, patients often require anesthesia to alleviate substantial discomfort. Currently, patients with similar degrees of scarring may choose surface anesthesia or general anesthesia based on their personal preferences. Nevertheless, the effectiveness and safety of different anesthesia modalities remain uncertain. OBJECTIVE: To assess the effectiveness and safety of both general and surface anesthesia in MPR treatment for hypertrophic scars. METHODS: We conducted a retrospective cohort study involving 101 patients diagnosed with hypertrophic scars who underwent MPR with different anesthesia methods. The primary measures of efficacy included the Vancouver Scar Scale (VSS) scores assessed before the first treatment and six months after the final treatment. Pain relief was evaluated using Visual Analog Scale (VAS) scores. Safety was assessed by comparing the incidence of adverse reactions between the two groups. RESULTS: Patients in the general anesthesia group showed a significant difference in scar pigmentation 6 months after the treatment and lower pain level than those in the surface anesthesia group in the treatment of MPR. The difference in safety was not statistically significant. After adjusting for confounding factors and propensity score matching, the outcome of VSS and VAS scores was stable. CONCLUSION: General anesthesia, as opposed to surface anesthesia, appears to enhance both the effectiveness and safety of MPR while reducing postoperative pain in the treatment of hypertrophic scars. For patients with heightened pain sensitivity, general anesthesia may be the preferred treatment option. LEVEL OF EVIDENCE II: 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 http://www.springer.com/00266 .

Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Facial cosmetic injection: A bibliometric analysis of research status and hotspots.

BACKGROUND: The increasing popularity of cosmetic injections using various fillers and neuromodulators for facial rejuvenation has brought both new opportunities and challenges to this field. AIM: Our study was designed to employ bibliometric and visual analysis for a qualitative and quantitative evaluation of facial cosmetic injections, as well as to identify research trends and hotspots in this field. METHODS: All publications covering facial cosmetic injection during 2002-2023 were retrieved and extracted from the Web of Science database. The VOSviewer 1.6.18 software and the online tool (http://bibliometric.com/) were applied to analyze the publication trend. RESULTS: A total of 3797 articles related to facial cosmetic injection were identified during the period 2002-2023. The United States had the largest volume of publications (1520, 40.0%), followed by China (333, 8.8%) and Germany (282, 7.3%). Among the institutions and journals, the University of California system and Plastic and Reconstructive Surgery accounted for the most papers related to facial cosmetic injection, respectively. Facial anatomy and injection techniques, prevention and management of complications, regenerative medicine, efficacy and safety of various soft-tissue fillers, as well as botulinum toxin injections for facial rejuvenation were identified as hotspots for facial cosmetic injections. CONCLUSIONS: Facial cosmetic injections are showing an increasing trend in terms of both the number of published papers and operations performed. Despite the notable advancements in this field, numerous challenges persist, including safety concerns and the level of research evidence. With the emergence of novel technologies and materials, scholars from diverse countries and institutions should engage in more extensive collaboration, thereby directly expediting the progress of this field.

Association of LOX gene G473A polymorphism with the occurrence of allergic rhinitis and efficacy of montelukast sodium in children.

Allergic rhinitis (AR) is very common in adolescents, and current treatment options are complex and unsatisfactory. The objective of this study was to analyze the association of lysyl oxidase (LOX) gene G473A polymorphism with susceptibility to AR in children. In addition, we analyzed the therapeutic effect of montelukast sodium on AR. Forty-five children with AR (research group, 8.16±2.88 years old) and 51 healthy children (control group, 8.22±3.87 years old) during the same period were selected. The LOX gene G473A polymorphism was detected with polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The effect of G473A polymorphism in the occurrence of AR was assessed by logistic regression analysis. In addition, the levels of C-reactive protein (CRP), Interleukin (IL-6), and IL-8 were measured to observe the relationship between G473A polymorphism and inflammatory factors. Finally, montelukast sodium was given to children with AR to investigate the effect of G473A polymorphism on clinical outcomes. The number of G473A polymorphisms in the research group was not significantly different from the control group for GA-type (P = 0.521). However, the number of GG-type polymorphisms was less while the number of type AA was more than the control group (P = 0.044 and 0.046). Children carrying the AA gene had an approximately 4-fold increased risk of AR, while those carrying the GG gene had a decreased risk (P < 0.001). Moreover, children carrying the GG gene had lower levels of CRP, IL-6, and IL-8 and better clinical outcomes, while those carrying the AA gene had higher levels of inflammatory factors and worse outcomes (P<0.05). LOX gene G473A polymorphism is closely associated with AR pathogenesis and may have an important research value in antagonizing the therapeutic effect of montelukast sodium.

Efficacy and Safety of Pressure Therapy Alone and in Combination with Silicone in Prevention of Hypertrophic Scars: A Systematic Review with Meta-analysis of Randomized Controlled Trials.

BACKGROUND: At present, there are many kinds of hypertrophic scar treatment methods, among which pressure therapy and silicone therapy are very common and standard therapies, but whether they are used alone or in combination is still controversial. Therefore, the purpose of this systematic review was to compare the efficacy and safety of the combination of pressure therapy and silicone therapy (PTS) with pressure therapy alone (PT) in the treatment of hypertrophic scars to provide clinicians with information so that they can make better decisions. METHODS: Relevant randomized controlled trials (RCTs) were collected by searching PubMed, Ovid MEDLINE, Embase, ScienceDirect, Web of Science, The Cochrane Library, Scopus, and Google Scholar databases to assess scar scores (The Vancouver Scar Scale, VSS; Visual Analog Scale, VAS) and adverse effects. RESULTS: We screened 1270 articles and included 6 RCTs including 228 patients. We found that height (MD = 0.15, 95%CI 0.10-0.21, p < 0.01) and pliability (MD = 0.35, 95%CI 0.25-0.46, p <0.01) had a significant difference, these two measures showed that the PTS group was superior to the PT group. Results in other aspects, such as VSS, vascularity, pigmentation, VAS, and adverse effects were similar between the two groups. CONCLUSIONS: There was no significant difference between PTS and PT in the overall treatment efficacy of hypertrophic scars with similar VSS and adverse effects, but PTS might have potential benefits for height and pliability. Additional studies with larger sample size and sound methodological quality are needed to confirm our conclusions. 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 .

3D-bioprinted human lipoaspirate-derived cell-laden skin constructs for healing of full-thickness skin defects.

29Three-dimensional (3D)-printed bioactive scaffolds that can be produced rapidly could offer an individualized approach for treating full-thickness skin defects. Decellularized extracellular matrix (dECM) and mesenchymal stem cells have been proven to support wound healing. Adipose tissues obtained by liposuction are rich in adipose-derived dECM (adECM) and adipose-derived stem cells (ADSCs) and thus represent a natural source of bioactive materials for 3D bioprinting. Herein, ADSC-laden 3D-printed bioactive scaffolds consisting of gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), and adECM were fabricated with dual properties of photocrosslinking in vitro and thermosensitive crosslinking in vivo. adECM was prepared by decellularization of human lipoaspirate and mixed as a bioactive material with GelMA and HAMA to form a bioink. Compared with the GelMA-HAMA bioink, the adECM-GelMA-HAMA bioink had better wettability, degradability, and cytocompatibility. Full-thickness skin defect healing in a nude mouse model showed that ADSC-laden adECM-GelMA-HAMA scaffolds accelerated wound healing by promoting faster neovascularization, collagen secretion, and remodeling. ADSCs and adECM collectively conferred bioactivity on the prepared bioink. This study represents a novel approach to enhancing the biological activity of 3D-bioprinted skin substitutes by adding adECM and ADSCs derived from human lipoaspirate and may provide a promising therapeutic option for full-thickness skin defects.

3D-Bioprinted Biomimetic Multilayer Implants Comprising Microfragmented Adipose Extracellular Matrix and Cells Improve Wound Healing in a Murine Model of Full-Thickness Skin Defects.

Repairing full-thickness skin defects is a major challenge in clinical practice. Three-dimensional (3D) bioprinting of living cells and biomaterials is a promising technique to resolve this challenge. However, the time-consuming preparation and limited sources of biomaterials are bottlenecks that must be addressed. Therefore, we developed a simple and fast method to directly process adipose tissue into a microfragmented adipose extracellular matrix (mFAECM) as the main component of bioink to fabricate 3D-bioprinted, biomimetic, multilayer implants. The mFAECM retained most of the collagen and sulfated glycosaminoglycans in the native tissue. In vitro, the mFAECM composite demonstrated biocompatibility, printability, and fidelity and could support cell adhesion. In a full-thickness skin defect model in nude mice, cells encapsulated in the implant survived and participated in wound repair after implantation. The basic structures of the implant were maintained throughout wound healing and gradually metabolized. The biomimetic multilayer implants fabricated via mFAECM composite bioinks and cells could accelerate wound healing by promoting the contraction of new tissue inside the wound, collagen secretion and remodeling, and neovascularization. This study provides an approach for improving the timeliness of fabricating 3D-bioprinted skin substitutes and may offer a useful tool for treating full-thickness skin defects.

Application of 3D-printed tissue-engineered skin substitute using innovative biomaterial loaded with human adipose-derived stem cells in wound healing.

Large-scale skin injuries are usually accompanied by impaired wound healing, resulting in scar formation, or significant morbidity and mortality. The aim of this study is to explore the in vivo application of 3D-printed tissue-engineered skin substitute using innovative biomaterial loaded with human adipose-derived stem cells (hADSCs) in wound healing. Adipose tissue was decellularized, and extracellular matrix components were lyophilized and solubilized to obtain adipose tissue decellularized extracellular matrix (dECM) pre-gel. The newly designed biomaterial is composed of adipose tissue dECM pre-gel, methacrylated gelatin (GelMA), and methacrylated hyaluronic acid (HAMA). Rheological measurement was performed to evaluate the phase-transition temperature and the storage and loss modulus at this temperature. Tissue-engineered skin substitute loaded with hADSCs was fabricated by 3D printing. We used nude mice to establish full-thickness skin wound healing model and divided them into four groups randomly: (A) Full-thickness skin graft treatment group, (B) 3D-bioprinted skin substitute treatment group as the experimental group, (C) microskin graft treatment group, and (D) control group. The amount of DNA in each milligram of dECM was 24.5 ± 7.1 ng, fulfilling the currently accepted decellularization criteria. The solubilized adipose tissue dECM was thermo-sensitive biomaterial and underwent a sol-gel phase transition when temperature rises. The dECM-GelMA-HAMA precursor undergoes a gel-sol phase transition at 17.5°C, where the storage and loss modulus of the precursor is about 8 Pa. The scanning electron microscope showed that the interior of crosslinked dECM-GelMA-HAMA hydrogel is 3D porous network structure with suitable porosity and pore size. The shape of the skin substitute is stable with regular grid-like scaffold structure. Wound healing in the experimented animals was accelerated after being treated with 3D-printed skin substitute, which attenuate inflammatory response, increase blood perfusion around the wound, as well as promote re-epithelialization, collagen deposition and alignment, and angiogenesis. In summary, 3D-printed dECM-GelMA-HAMA tissue-engineered skin substitute loaded with hADSCs, which can be fabricated by 3D printing, can accelerate wound healing and improve healing quality by promoting angiogenesis. The hADSCs and the stable 3D-printed stereoscopic grid-like scaffold structure play a critical role in promoting wound healing.

Post-rhinoplasty complications with previous hyaluronic acid injection history: Cerebral infarction and vision loss.

BACKGROUND: Rhinoplasty is becoming increasingly frequent as the pursuit of aesthetics by people accelerates. In recent years, the proportion of people opting for rhinoplasty injections has gradually increased. This has led to numerous reports citing catastrophic postoperative complications such as skin necrosis, cerebral infarction, and visual impairment. AIM: The aim of our report is to discuss the possible etiological factors for this post-rhinoplasty complication and provides a rationale for HA injection history as a risk factor in rhinoplasty. METHODS: We report a rare case that received nasal HA injections in the past without any untoward incident. She opted for a second rhinoplasty 2 years after her initial nasal HA injections. This second intervention led to post-injection loss of vision in one eye and cerebral infarction. Following clinical and radiological examination, digital subtraction angiography (DSA) and superselective intra-arterial thrombolysis were performed. RESULTS: The patient did not develop disuse exotropia or ocular atrophy, but the left eye remained without light perception, which implies that intra-arterial thrombolytic therapy may be a positive and effective method to maintain the normal appearance of the eye. CONCLUSION: It is advisable for patient safety to maintain a long interval of time between hyaluronidase injection and repeat rhinoplasty. Clinicians should become familiar with the anatomical peculiarities of the patient and be gentle during the rhinoplasty procedure.

Splint-free line drawing model: An innovative method for excisional wound models.

The physiological phenomenon of wound contraction in mice cannot completely imitate the process of human skin regeneration, which is primarily attributed to reepithelialisation. As such, excisional wound models in mice are considered to be imperfect comparisons. This study aimed to enhance the correlation of mouse excisional wound models with that of humans, and to offer more practical and accurate ways to record and measure wound areas. We present evidence that simple excisional wounds produce a robust and stable wound model by comparing splint-free and splint groups. We monitored reepithelialisation and contraction in the C57BL/6J mouse excision wound model at different time points and prove that excisional wounds heal by both contraction and reepithelialisation. Some parameters were measured and a formula was used to calculate the area of wound reepithelialisation and contraction. In our results, reepithelialisation accounted for 46% of the wound closure of full-thickness excisional wounds. In conclusion, excisional wound models can be used as wound-healing models and a straightforward formula may be used to determine the process of reepithelialisation over a wound bed created by a simple excisional rodent wound model.