Integrating multiomics sequencing analyses uncover the key mechanisms related to oxidative stress, mitochondria, and immune cells in keloid.

BACKGROUND: This study aimed to investigate the key molecular mechanisms underlying keloid pathogenesis by integrating oxidative stress, mitochondria, and immune cells. METHODS: Transcriptome sequencing (mRNA, lncRNA, and circRNA expression data), proteomic sequencing, and small RNA sequencing analyses of lesional and non-lesional skin of patients with keloids and healthy control (normal) skin were conducted. By integrating mRNA and publicly available gene expression data (GSE158395), differentially expressed genes related to oxidative stress and mitochondrial function in keloids were identified. Hub genes were identified using various bioinformatics analyses such as immune infiltration analysis, weighted gene co-expression network analysis, machine learning, and expression validation using proteomics sequencing data. Moreover, a competing endogenous RNA (ceRNA) network of hub genes was constructed by combining miRNA, lncRNA, and circRNA expression data. Five hub genes were identified: MGST1, DHCR24, ALDH3A2, ADH1B, and FKBP5. RESULTS: These hub genes had a high diagnostic value for keloids, with an AUC value > 0.8 each. In addition, five hub genes were associated with the infiltration of multiple immune cells. The immune cells with the strongest positive and negative correlations with hub genes were M0 and M1 macrophages. A ceRNA network was constructed, and several ceRNAs, such as AC005062.1/miR-134-5p/FKBP5 and BASP1-AS1/miR-503-5p/ADH1B, were identified. These five hub genes may contribute to keloid pathogenesis. CONCLUSION: These genes and their related ceRNAs may serve as diagnostic biomarkers and therapeutic targets for keloids.

Treatment benefit of electrochemotherapy for superficial squamous cell carcinoma: a systematic review and single-arm meta-analysis.

OBJECTIVE: Treating aggressive superficial squamous cell carcinoma (SCC) poses challenges due to invasiveness. Palliative care is recommended for inoperable cases with extensive tumors near vital organs, risking disfigurement or functional impairment. Electrochemotherapy (ECT) is an emerging cutaneous tumor treatment, but its efficacy against superficial SCC remains uncertain. This study conducts a systematic review and single-arm meta-analysis to evaluate ECT's effectiveness against superficial SCC and provide current evidence for clinical practice. METHODS: Embase, PubMed and Cochrane Library were searched for studies up to May 2023. The random effects model analyzed complete response (CR) and partial response (PR), with subgroup assessment based on drug dosage, treatment response evaluation, tumor size, primary/recurrent status, and tumor location. RESULTS: Ten studies involving 162 patients and 208 tumors were included. Pooled CR and PR rates for ECT-treated superficial SCC were 66.5% (95% CI 48.4%-82.5%; I2 = 84%) and 20.3% (95% CI 10.5%-32.3%; I2 = 70%), respectively. Subgroup analysis indicated ECT's superiority in treating primary tumors (PR: 70%, CR: 30%) and tumors ≤ 3 cm (PR: 81.3%, CR: 10.1%) compared to recurrent tumors (PR: 56.7%, CR: 36.5%) and tumors > 3 cm (PR: 45.2%, CR: 34.4%). CONCLUSION: This single-arm meta-analysis confirms ECT's efficacy against superficial SCC, especially in primary tumors and those ≤ 3 cm in diameter. The study highlights the impact of tumor location and response evaluation on ECT's benefits, warranting further investigation through additional research.

Integrated transcriptome sequencing and weighted gene co-expression network analysis reveals key genes of papillary thyroid carcinomas.

Objective: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers and has a high recurrence rate. We aimed to screen key genes involved in PTC to provide novel insights into the mechanisms of PTC. Methods: Seven microarray datasets of PTC were downloaded from gene expression omnibus database. Differentially expressed genes (DEGs) between PTC and normal samples were screened in the merged dataset. Then, protein-protein interaction (PPIs) functional modules analysis and weighted gene co-expression network analysis (WGCNA) were utilized to identify PTC-associated key genes. The identified key genes were then characterized from various aspects, including gene set enrichment analysis (GSEA) and the associations with immune infiltration, methylation levels and prognosis. Results: A large numbers of DEGs were identified, and these DEGs are involved in several cancer pathways. Nine key genes (including down-regulated genes GNA14, AVPR1A, and WFS1, and up-regulated genes LAMB3, PLAU, MET, MFGE8, PRSS23, and SERPINA1) were identified. Patients in the AVPR1A and GNA14 high expression groups had better disease-free survival (DFS) than those in the low expression group. Key genes were mainly involved in P53 pathway, estrogen response, apoptosis, glycolysis, NOTCH signaling, epithelial mesenchymal transition, WNT_beta catenin signaling, and inflammatory response. The expression of key genes was associated with immune cell infiltration and corresponding methylation levels. The verification results of key gene proteins and mRNA expression levels using external validation datasets were consistent with our expectations, implying the involvements of key genes in PTC. Conclusion: The key genes may serve as potential therapeutic targets for PTC. This study provides novel insights into the mechanisms underlying PTC development.

A novel antagonist of the CCL5/CCR5 axis suppresses the tumor growth and metastasis of triple-negative breast cancer by CCR5-YAP1 regulation.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC) with a high mortality rate, and few effective therapeutic strategies are available. CCL5/CCR5 is an appealing immunotherapeutic target for TNBC. However, its signaling mechanism is poorly understood and its direct antagonists have not been reported. Here, we developed a high-throughput screening (HTS) assay for discovering its antagonists. Verteporfin was identified as a more selective and potent antagonist than the known CCR5 antagonist maraviroc. Without photodynamic therapy, verteporfin demonstrated significant inhibition on TNBC tumor growth through immune regulation, remarkable suppression of lung metastasis by cell-intrinsic mechanism, and a significant extension of overall survival in vivo. Mechanistically, CCR5 was found to be essential for expression of the key hippo effector YAP1. It promoted YAP1 transcription via HIF-1α and exerted further control over the migration of CD8+ T, NK, and MDSC immune cells through chemokines CXCL16 and CXCL8 which were identified from RNA-seq. Moreover, the CCR5-YAP1 axis played a vital role in promoting metastasis by modulating ß-catenin and core epithelial-mesenchymal transition transcription factors ZEB1 and ZEB2. It is noteworthy that the regulatory relationship between CCR5 and YAP1 was observed across various BC subtypes, TNBC patients, and showed potential relevance in fifteen additional cancer types. Overall, this study introduced an easy-to-use HTS assay that streamlines the discovery of CCL5/CCR5 axis antagonists. Verteporfin was identified as a specific molecular probe of this axis with great potentials as a therapeutic agent for treating sixteen malignant diseases characterized by heightened CCR5 and YAP1 levels.

Inhibition of Proliferation, Migration, and Invasion of Keloid Fibroblasts By miR-183-5p Through Downregulating EGR1 / Inhibición de la Proliferación, Migración e Invasión de Fibroblastos Queloides por miR-183-5p Mediante la Regulación Negativa de EGR1

SUMMARY: Keloid scar is a unique benign fibroproliferative tumor of the human skin. Previously, it was reported that early growth response 1 (EGR1), a transcription factor, promotes keloid fibrosis; however, the mechanism by which EGR1 modulates keloid formation was not elaborated. In this research, the specific function and the microRNA (miRNA) regulatory network of EGR1 in keloids was examined. Keloid fibroblasts (KFs) were transfected with EGR1-small interfering RNA (siEGR1), EGR1-overexpression plasmid (pcDNA3.1-EGR1), and microRNA (miR-183-5p)-mimics to regulate the expression of EGR1 and miR-183-5p. The study employed dual-luciferase reporter assays to explore the targeting regulation of miR-183-5p on EGR1. Additionally, Western blotting, flow cytometry, qRT-PCR, cell count kit-8 (CCK-8), transwell, and wound healing assays, and RNA sequencing were conducted. EGR1 was upregulated in KFs, and EGR1 silencing diminished proliferation, fibrosis, migration, invasion, and apoptosis of cells. In KFs, the expression of miR- 183-5p was reduced, leading to the inhibition of cell proliferation, migration, and invasion. Conversely, it enhanced apoptosis. By targeting EGR1, miR-183-5p partially counteracted the impact of EGR1 on migration, invasion, and fibrosis in KFs. The findings imply that miR-183-5p suppresses keloid formation by targeting EGR1. As a result, EGR1 holds promise as a potential therapeutic target for preventing and treating keloids.

La cicatriz queloide es un tumor fibroproliferativo benigno único de la piel humana. Anteriormente, se informó que la respuesta de crecimiento temprano 1 (EGR1), un factor de transcripción, promueve la fibrosis queloide; sin embargo, no se explicó el mecanismo por el cual EGR1 modula la formación de queloides. En esta investigación, se examinó la función específica y la red reguladora de microARN (miARN) de EGR1 en queloides. Se transfectaron fibroblastos queloides (KF) con ARN de interferencia pequeño de EGR1 (siEGR1), plásmido de sobreexpresión de EGR1 (pcDNA3.1-EGR1) y miméticos de microARN (miR-183-5p) para regular la expresión de EGR1 y miR-183. -5p. El estudio empleó ensayos de indicador de luciferasa dual para explorar la regulación dirigida de miR-183-5p en EGR1. Además, se realizaron pruebas de transferencia Western, citometría de flujo, qRT-PCR, kit de recuento celular-8 (CCK-8), transwell y curación de heridas, y secuenciación de ARN. EGR1 estaba regulado positivamente en KF, y el silenciamiento de EGR1 disminuyó la proliferación, fibrosis, migración, invasión y apoptosis de las células. En KF, la expresión de miR- 183-5p se redujo, lo que llevó a la inhibición de la proliferación, migración e invasión celular. Por el contrario, mejoró la apoptosis. Al apuntar a EGR1, miR-183-5p contrarrestó parcialmente el impacto de EGR1 en la migración, invasión y fibrosis en KF. Los hallazgos implican que miR-183-5p suprime la formación de queloides al apuntar a EGR1. Como resultado, EGR1 es prometedor como objetivo terapéutico potencial para prevenir y tratar los queloides.

Micro-plasma radiofrequency and silicone gel dressings for treating early post-traumatic facial scars: A retrospective study.

BACKGROUND: Although different options are available for treating post-traumatic facial scars, they remain a therapeutic challenge. AIM: To evaluate the safety and effectiveness of combined therapy using micro-plasma radiofrequency (MPRF) technology and silicone gel (SG) dressings for treating post-traumatic facial scars. METHODS: This retrospective study was conducted at a single center. Patients with facial injuries in the outpatient and emergency units of the Department of Plastic Surgery at our hospital underwent debridement and cosmetic sutures performed by the same surgeon from October 2020 to October 2021. In the first arm, patients with facial injuries were treated with MPRF technology and SG, and in the second arm, they were treated with SG dressings alone. We observed the safety and effectiveness of these treatments in both arms. RESULTS: A total of 32 patients with facial injuries were treated with MPRF technology and SG dressings (combined treatment group), and 28 patients were treated with SG dressings alone (SG group). After 6 months of treatment, the Vancouver Scar Scale scores of the combined treatment and SG groups were 1.38 ± 0.71 and 4.39 ± 0.50, respectively, and the difference was statistically significant (P < 0.01). After 6 months of treatment, the effectiveness rate in the combined treatment group was 93.8%, which was significantly higher than that in the SG group (67.9%), and the difference between the two groups was statistically significant (P < 0.05). No obvious adverse reactions occurred in the two arms. CONCLUSION: Treating early post-traumatic facial scars with combined MPRF technology and SG is significantly better than treating them with SG alone; moreover, the combined therapy is safe and effective.

The effect of double W tension-reduced suture technique on the abdominal scars following the da Vinci robot-assisted gastrectomy for severely obese patients.

OBJECTIVE: To analyze the effect of a new type of tension-reduced suture named "double W tension-reduced suture technique" on the abdominal scars following the da Vinci robot-assisted gastrectomy for severely obese patients. METHODS: 40 abdominal incisions following the da Vinci robot-assisted gastrectomy on severely obese patients from September 1st, 2021 to March 1st, 2022 were comprised in the study. 20 incisions were closed by the conventional full-thickness surgical suture as the control group, and 20 incisions were sewn up by double W tension-reduced suture as the double W group. The scars were assessed at the 1-month follow-up visit using the Vancouver scar scale (VSS), ultrasound and patient satisfaction. Meanwhile, digital photographs of scars were taken as well. RESULTS: The VSS score was 6.80 ± 2.16 in the control group, while that of the double W group was 2.60 ± 1.89. The difference between groups was significant. Digital photographs showed that the scar color was not only light and close to the skin color, but also flat and soft in the double W group. Ultrasound showed that the fibers of subcutaneous tissue in the double W group were arranged neatly, the ultrasonic signal intensity was relatively uniform, and the tunnel was small without obvious lacunae. More patients were satisfied and very satisfied with scars in the double W group. CONCLUSION: Double W tension-reduced suture technique could significantly improve the appearance and reduce comorbidities of scars following the da Vinci robot-assisted gastrectomy for severely obese patients.

An umbrella review of the use of platelet-rich plasma in the treatment of androgenetic alopecia.

OBJECTIVE: To evaluate the efficacy of platelet-rich plasma (PRP) in the treatment of androgenetic alopecia, as well as establish an effective treatment protocol and optimal PRP preparation procedure. METHODS: We searched the PubMed, Scopus, Embase, Cochrane, CNKI, and Wanfang databases from inception to October 29, 2021, using PROSPERO's International Prospective Register of Systematic Reviews (registration ID: CRD42022295921). RESULTS: The original literature search revealed 215 reviews; after duplication removal, 89 papers were eliminated, 95 were eliminated after reading the titles and abstracts, and eventually, 28 articles were included after reading the complete text. CONCLUSIONS: PRP treatment for androgenetic alopecia is effective, and we recommend the following: (1) a PRP volume of at least 0.05 ml/cm2 , preferably 0.1 ml/cm2 ; (2) at least three consecutive treatments at an interval of 1 month; (3) intensive therapy is beneficial and can be provided from 3 to 6 months after continuous treatment; (4) objective indicators such as hair diameter, hair count; (5) long-term follow-up.

Buccal Fat Pad Transplantation for Correction of Asian Upper Eyelid Depression: A Clinical Study.

OBJECTIVES: To investigate the effect of buccal fat pad transplantation in front of the aponeurosis to correct Asian upper eyelid depression. METHODS: Eighty-five individuals who were treated with buccal fat pad transplantation were recruited for this study. The upper eyelid depression data were collected before and after treatment, and the aesthetic outcomes were assessed using the Global Aesthetic Improvement Scale (GAIS) and the Likert scale. RESULTS: All patients obtained natural-looking eyelids, and the sunken contour deformity improved. The mean preoperative sunken depth was 6.7±1.0 mm (4-12 mm), and the mean sunken depth at the last follow-up was 4.2±0.9 mm (2-6 mm) (P <0.05). The visual analogue scale score was 2.12±1.75 (1-4) in the immediate postoperative period. The GAIS scores were satisfactory (very much improved, 89.4%; much improved, 7.1%; and improved, 3.5%). According to the Likert scale scores, all patients were satisfied with the clinical outcomes (excellent, 87.1%; very good, 9.4%; and good, 3.5%). A 'fair' or 'poor' result was not reported by any patient. CONCLUSION: Buccal fat pad transplantation corrects upper eyelid depression in a simple, safe, and effective manner and can efficiently fill the depressed portion and restore a beautiful double eyelid. LEVEL OF EVIDENCE V: 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 .

Current knowledge and future perspectives on exosomes in the field of regenerative medicine: a bibliometric analysis.

Objective: This study aimed to use bibliometric analysis to qualitatively and quantitatively evaluate the research of exosomes in the field of regenerative medicine and to provide research hotspots and trends in this field. Materials & methods: Bibliometric analysis and data presentation were performed by VOSviewer and Microsoft Excel. Results: China was the major contributor to research in this field and enjoys a high reputation in academia. The highest contributing institution is Shanghai Jiao Tong University. Research hotspots included exosome-mediated neurovascular regeneration, exosome mechanism research, exosome-mediated cartilage regeneration and repair and exosome-mediated cardiac regeneration. Research was trending in the treatment of osteoarthritis, knee disease and cartilage regeneration and repair. Conclusion: This study provides a panoramic view of the application of exosomes in regenerative medicine.

Exosomes have been extensively studied in regenerative medicine. However, a bibliometric analysis of exosomes in this field is lacking. The purpose of this study was to conduct a bibliometric analysis of the research on exosomes in regenerative medicine from 2010 to 2021 and to identify important research through hot keywords, active authors, countries/regions, institutions, published journals, citations and cooperation. The authors retrieved 1383 articles from the Web of Science Core Collection database. Through analysis with VOSviewer software, the authors found the research hotspots and trends of exosomes in the field of regenerative medicine, as well as the countries, authors and journals that have made major contributions. This novel comprehensive bibliometric analysis can help researchers quickly identify hotspots and research trends in this field.

Current Knowledge and Future Perspectives of Buttock Augmentation: A Bibliometric Analysis from 1999 to 2021.

BACKGROUND: The number of patients undergoing buttock augmentation surgery has increased rapidly with time, changes in people's aesthetic perceptions, and the increased concern for their shape. The number of publications regarding buttock augmentation has also continued to increase. However, no bibliometric analysis concerning buttock augmentation has been published. This study aimed to provide a qualitative and quantitative evaluation of buttock augmentation-related publications using bibliometric analysis and information on research hotspots and trends in this field. METHODS: The buttock augmentation-related publications published between 1999 and 2021 were extracted from the Web of Science Core Collection (WOSCC) database for analysis. The data were analysed and presented using VOSviewer and Microsoft Excel. RESULTS: There were 492 articles in the (WOSCC) database, including 442 (89.84%) original research articles, with the number of publications increasing each year. The USA (208 publications, 42.28%) is the leading contributor in this field and has a high academic reputation. The most productive and co-cited journal on this subject is "Plastic and Reconstructive Surgery" (66 publications, 13.41%, 2200 citations). Cardenas-Camarena (9 publications, 1.83%, 158 citations) was the most published and co-cited author. Research hotspots include the following three topics: experience and technology of buttock augmentation, autologous fat buttock augmentation and its safety, and buttock aesthetics study. There will be more publications in the future, and research trends will focus on silicone implants, safety, satisfaction, and autologous fat grafting. CONCLUSION: Buttock augmentation research is rapidly evolving, and this study provides a perspective view of buttock augmentation research in Plastic and Reconstructive Surgery. 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 www.springer.com/00266 .

C1QA, C1QB, and GZMB are novel prognostic biomarkers of skin cutaneous melanoma relating tumor microenvironment.

Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancers owing to high invasiveness and high metastatic potential. Tumor microenvironment (TME) provides powerful evidences for discerning SKCM, raising the prospect to identify biomarkers of SKCM. Based on the transcriptome profiles of patients with SKCM and the corresponding clinical information from The Cancer Genome Atlas (TCGA), we used ESTIMATE algorithm to calculate ImmuneScore and StromalScore and identified the TME-Related differentially expressed genes (DEGs), than the intersected TME-Related DEGs were used for subsequent functional enrichment analysis. Protein-protein interaction (PPI) analysis was used to identify the functionality-related DEGs and univariate Cox regression analysis was used to identify the survival-related DEGs. Furthermore, SKCM-related DEGs were identified based on two Gene Expression Omnibus (GEO) datasets. Finally, we intersected functionality-related DEGs, survival-related DEGs, and SKCM-related DEGs, ascertaining that six DEGs (CCL4, CXCL10, CCL5, GZMB, C1QA, and C1QB) function as core TME-related genes (CTRGs). Significant differences of GZMB, C1QA, and C1QB expressions were found in gender and clinicopathologic staging of SKCM. High levels of GZMB, C1QA, and C1QB expressions were associated with favorable prognosis. Gene set enrichment analysis (GSEA) showed that cell-cell interaction, cell behavior, and intracellular signaling transduction may be mainly involved in both C1QA, C1QB and GZMB expressions and metabolism of phospholipid and amino acid, transcription, and translation may be implicated in low GZMB expressions. C1QA, C1QB, and GZMB are novel SKCM-relating CTRGs, providing promising immune-related prognostic biomarkers for SKCM.

Integrative analyses of immune-related biomarkers and associated mechanisms in coronary heart disease.

Various studies showed that the effect of immune activation is pro-atherogenic and coronary heart disease (CHD) should therefore be considered an autoimmune disease. This study aimed to identify potential immune-related biomarkers, pathways, and the potential regulatory networks underlying CHD. Differentially expressed genes (DEGs) between CHD and control samples were determined by analyzing GSE71226 and GSE9128. The overlapping differential expression immune-related genes (DE-IRGs) for CHD were identified by analyzing the ImmPort database and two GEO databases. A total of 384 DE-IRGs were identified. Subsequently, comprehensive enrichment analyses suggested that DE-IRGs were enriched in immune-related pathways, including autoimmune thyroid disease, the intestinal immune network for IGA production, and downstream signaling events of B cell receptors. The signature of DE-IRGs was validated using an external independent dataset GSE20681 (AUC = 0.875). Furthermore, we conducted protein-protein interaction network analysis and identified eight hub genes, which were most enriched in regulation of defense response, NF-κB signaling pathway, regulation of JNK cascade, and regulation of cytokine production. Moreover, networks of miRNAs-mRNAs and transcription factors (TFs)-mRNA underlying the integrated data were established, involving eight miRNAs and 76 TF-targeting hub genes. Ultimately, 17 SNPs in miRNA-mediated gene networks were identified. We screened potential immune-related genes in CHD and constructed miRNA-mRNA-TF and SNP-miRNA networks, which not only provide inspired insights into the occurrence and the molecular mechanisms of CHD but also lay a foundation for targeting potential biomarkers using immunotherapy and for understanding the molecular mechanisms of CHD.

Efficacy of the Neodymium-Doped Yttrium Aluminum Garnet Laser in the Treatment of Keloid and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Keloid and hypertrophic scars are the most common types of pathological scars. They can cause itching, pain, erythema, and psychological stress due to cosmetic problems, decreasing the quality of life for affected individuals. The neodymium-doped yttrium aluminum garnet (Nd:YAG) multipurpose laser is used to treat pathological scars, and studies have shown that the Nd:YAG laser can markedly improve scarring. AIMS: We performed a meta-analysis to evaluate the efficacy of the Nd:YAG laser in the treatment of keloid and hypertrophic scars. METHODS: A literature search of PubMed, Web of Science, Scopus, Cochrane, Embase, CNKI, and Wanfang was performed between January 1st, 2010, and July 14th, 2021. The Vancouver Scar Scale (VSS) was used to evaluate treatment outcomes. We used the R version 4.0.0 software for statistical analysis. RESULTS: The Nd:YAG laser improved the condition of keloid and hypertrophic scars and reduced VSS score (mean difference [MD]: 2.96, 95% confidence interval [CI]: 2.08-3.84, p < 0.01). There was no obvious difference in the results between regions. A subgroup analysis by scar type revealed that the curative effect of the Nd:YAG laser on keloid scars (MD: 2.02, 95% CI: 0.58-4.63, p = 0.10) was less marked compared with that on hypertrophic scars (MD: 3.05, 95% CI: 1.58-4.52, p < 0.01). With the combined use of the Nd:YAG laser and other treatment methods, a more significant change in VSS score was noted (MD: 4.28, 95% CI: 2.07-6.49). CONCLUSIONS: This meta-analysis showed that the Nd:YAG laser can improve the condition of keloid and hypertrophic scars and effectively reduce VSS score. Moreover, the curative effect of this approach on keloid scars is less marked compared with that on hypertrophic scars. 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 www.springer.com/00266.

EGR1/NOX4 pathway regulates oxidative stress and further facilitates fibrosis progression in keloids responses to TGF-ß1.

BACKGROUND: As classic benign fibroproliferative tumors, keloids remain a major therapeutic challenge due to their complex pathological mechanisms. OBJECTIVE: To determine the functional role of transforming growth factor ß1 (TGF-ß1)/early growth response factor-1 (EGR1)/NADPH oxidases 4 (NOX4) axis in the pathogenesis of keloid fibrosis. METHODS: Differentially expressed genes in keloid tissues and normal skins were analyzed by RNA sequencing. Then, the human skin fibroblast cell line was treated with TGF-ß1 at a dose of 10 ng/mL in order to stimulate the TGF-ß1/SMAD pathway and the pathway was blocked using the SB431542. Furthermore, EGR1/NOX4 was over-expressed and inhibited by transfecting overexpression plasmids and small interfering RNAs, respectively. The levels of intracellular reactive oxygen species were measured using the DCFH-DA assay, and the expression levels of fibrosis-related genes were assessed by Western blot analysis. Alternately, dual-luciferase reporter analysis verified the targeting relationship between EGR1 and NOX4. RESULTS: The TGF-ß1/SMAD signaling pathway was significantly activated in keloid tissues to promote dermal fibrosis. The level of ROS was increased in keloid fibroblasts. Moreover, TGF-ß1 could facilitate the expression of EGR1 through regulating the SMAD pathway in keloids and promoting the fibrotic phenotype of keloid fibroblasts. EGR1 could regulate the production of ROS by targeting NOX4. Furthermore, NOX4-derived ROS could promote fibrotic-like phenotype of keloid fibroblasts and play an important role in keloid fibrosis. CONCLUSION: Our findings provide new insights into the mechanisms of the TGF-ß1/EGR1/NOX4 pathway in keloid fibrosis, and the TGF-ß1/EGR1/NOX4 axis may serve as a potential therapeutic target for keloids.

Safety and efficacy of botulinum toxin type A in preventing and treating scars in animal models: A systematic review and meta-analysis.

Previous studies have used botulinum toxin type A (BTXA) to improve postoperative and hypertrophic scars; however, there is lack of detailed verification on the safety and effectiveness of this approach. This study aimed to evaluate the therapeutic effect of BTXA on postoperative hypertrophic scars and its influence on cytokine expression in animal models. A computerised search of different databases was performed, including PubMed, Web of Science, Scopus, Cochrane, Embase, CNKI, and Wanfang, up to 10 March 2021. A meta-analysis was performed using R 4.0.0 based on hypertrophic index, epithelialisation time, wound area, and vascular endothelial growth factor (VEGF) expression. Eleven studies were included. The meta-analysis showed a significant difference in hypertrophic index (standardised mean difference [SMD] = -2.63, 95% confidence interval [CI]: -3.50 to -1.76, P < .01), wound area (SMD = -0.54, 95% CI: -1.24 to 0.16, P < .01), and VEGF expression (SMD = -2.56, 95% CI: -3.50 to -1.62, P < .01). This study shows that BTXA is safe and effective in preventing and treating scar hypertrophy in animal models, but excessive doses of BTXA and BTXA to treat large areas should be avoided.

Ultrasound-guided five-point injection of botulinum toxin for patients with trapezius hypertrophy.

OBJECTIVES: Our study aimed to explore the clinical therapeutic effects of ultrasound-guided five-point injection of botulinum toxin type A for patients with trapezius hypertrophy. METHODS: Twenty female patients diagnosed with trapezius hypertrophy were enrolled in this study. The thicknesses of the trapezius muscle were measured by using the ultrasound scanner to locate the thickest point of trapezius, followed by labelling the other four points around the first point. Botulinum toxin type A was injected bilaterally (50 IU/side, 5 points/side) in the trapezius muscle of these patients. The surgery effects were evaluated by thicknesses of the trapezius muscle, intramuscular needle electromyographic and electroneurographic examinations, appearance changes and patients' satisfactions. RESULTS: Statistically significant differences in thicknesses of the trapezius muscle were observed at 4 weeks (p < 0.001), 12 weeks (p < 0.001), 20 weeks (p < 0.001), 28 weeks (p = 0.011), 36 weeks (p = 0.022), and 44 weeks (p = 0.032) after surgery. The latencies of trapezius muscle became longer at 12 weeks after surgery (left: 2.40 ms, right: 2.53 ms vs. left: 1.75 ms, right: 2.00 ms). Electroneurographic results showed amplitude reduction of compound muscle action potentials (CMAPs) at 12 weeks after surgery (left: 1.91 uV, right: 3.10 uV vs. left: 15.00 uV, right: 15.40 uV). Obvious appearance changes were revealed at 12 weeks after surgery. All of 80% patients were very satisfied, 15% patients were relatively satisfied, and 5% patients were not satisfied with the surgery. CONCLUSION: Ultrasound-guided five-point injection of botulinum toxin type A might be effective for patients with trapezius hypertrophy.

Treatment of axillary bromhidrosis in adolescents by combining electrocauterization with ultrasound-guided botulinum toxin type A injection.

The aim of this study is to investigate the efficacy of treatment-combined electrocauterization after removal of apocrine sweat glands with ultrasound-guided (BOTOX) injection for adolescents with axillary bromhidrosis. From January 2015 to January 2018, 90 adolescents with axillary bromhidrosis were recruited and randomly divided into three groups (group A, B, and C). Patients in group A underwent electrocauterization after removal of apocrine sweat glands, patients in group B received ultrasound-guided BOTOX injection, and patients in group C had electrocauterization after the removal of apocrine sweat glands followed by ultrasound-guided BOTOX administration after two weeks. All patients were followed up for one year. The percentages of axillary malodor score at twelve months after treatments compared with pre-operation for group A, group B, and group C were 20.2%, 27.5%, and 12.5%, respectively. Significant statistical differences were observed in changes of axillary malodor score among the three groups at three, six, nine and twelve months postoperatively. Satisfaction rates of group A, group B, and group C were 90.0%, 93.3%, and 96.7%, respectively. The side effects after surgery in group A were similar to group C, and no side effect was observed in group B. One-year postoperative scar formation rate of group A was 16.7%, which was significantly higher than that of group B (0) and group C (6.66%). Combination of electrocauterization after removal of apocrine sweat glands with ultrasound-guided BOTOX injection showed better treatment effects.

Comparison of primary keloid fibroblast cultivation methods and the characteristics of fibroblasts cultured from keloids, keloid-surrounding tissues, and normal skin tissues / Comparación de los métodos de cultivo de fibroblastos queloides primarios y las características de los fibroblastos cultivados a partir de queloides, tejidos circundantes queloides y tejidos cutáneos normales

SUMMARY: The establishment of primary keloid fibroblast culture has always been a fundamental measure for studying mechanisms of keloid disease. The quality of the primary cell culture can directly affect the results of further experiments. This study was performed to investigate the optimal growth conditions, including the optimal storage time and collagenase treatment time, for in vitro cell culture models and the suitable methods for epidermis-dermis separation in different tissues. Keloid tissues, keloid-surrounding tissues, and normal skin tissues were collected from patients, for primary fibroblast culture. Two methods, tissue explant and collagenase digestion, were deployed and compared. Expression levels of the keloid-related genes α -SMA, Col1, and Col3 were assessed in cells cultured using both methods, to verify the qualities of the primary cells. A comparative analysis was conducted between the two methods and among the three different tissues used. Bacterial and lipid contamination was immediately minimized after the samples were processed. Different methods of epidermis removal and different durations of collagenase digestion were required in different tissues to generate optimal results. Real-time PCR results showed that the mRNA expression levels of keloid-related genes in cultured fibroblasts correlated to their in vivo expression profile, as previously reported in other studies. The results of this study have revealed several key points in the culture of primary keloid fibroblasts and demonstrated the correlation in gene expression between in vivo keloid fibroblasts and in vitro primary keloid fibroblasts.

RESUMEN: La identificación de un cultivo de fibroblastos queloides primarios, siempre ha sido una medida fundamental para estudiar los mecanismos de la enfermedad queloide. La calidad del cultivo de células primarias puede afectar directamente los resultados de otros experimentos. Este estudio se realizó para investigar las condiciones óptimas de crecimiento, incluido el tiempo óptimo de almacenamiento y el tiempo de tratamiento con colagenasa, para modelos de cultivo celular in vitro y los métodos adecuados para la separación epidermis-dermis en diferentes tejidos. Se recogieron de los pacientes tejidos queloides, tejidos circundantes queloides y tejidos cutáneos normales, para cultivo primario de fibroblastos. Se implementaron y compararon dos métodos, explante de tejido y digestión con colagenasa. Los niveles de expresión de los genes relacionados con queloides α -SMA, Col1 y Col3 se evaluaron en células cultivadas usando ambos métodos, para verificar las cualidades de las células primarias. Se realizó un análisis comparativo entre los dos métodos y entre los tres tejidos diferentes utilizados. La contaminación de bacterias y lípidos se minimizó inmediatamente después de que se procesaron las muestras. Se requirieron varios métodos de eliminación de la epidermis y diferentes tiempos de digestión con colagenasa en los tejidos para generar resultados óptimos. Los resultados de la PCR en tiempo real mostraron que los niveles de expresión de ARNm de genes relacionados con queloides en fibroblastos cultivados se correlacionaban con su perfil de expresión in vivo, como se informó en estudios anteriores. Los resultados de este studio indicaron varios puntos clave en el cultivo de fibroblastos queloides primarios y han demostrado la correlación en la expresión génica entre fibroblastos queloides in vivo y fibroblastos queloides primarios in vitro.