Using network pharmacology to discover potential drugs for hypertrophic scars.

BACKGROUND: Hypertrophic scar is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation, and existing drugs cannot achieve satisfactory therapeutic effects. OBJECTIVES: This study aimed to explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for hypertrophic scars. METHODS: Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model. RESULTS: WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, transforming growth factor ß (TGF-ß) signaling pathway, and other biological pathways. Integrin ß1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib, and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and pro-fibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA (siRNA) can also inhibit mouse scar hyperplasia. CONCLUSIONS: ITGB1 and TGF-ß signaling pathways are important for hypertrophic scar formation. Crizotinib could serve as a potential drug for hypertrophic scars.

The Buried Guide Suture Method: A Novel Technique to Correct Traumatic Facial Dimples.

SUMMARY: Facial dimpling, frequently occurring after blunt trauma, presents as soft-tissue depression, which is particularly apparent during facial expression. The displacement of subcutaneous tissue can be detected and measured by high-frequency ultrasound. Limited surgical methods have been applied in these closed-injury cases. Repositioning the subcutaneous tissue without incisions on unscarred skin is challenging. The authors propose a novel three-dimensional technique to suture and fix the subcutaneous tissue at a distance through a concealed incision. The buried guide suture method was used in the treatment of 22 patients with traumatic facial dimples on the cheek. All patients showed great improvement in their depressed deformity with minor complications. This technique provides an option to correct soft-tissue depression without leaving a visible scar, especially for mimetic rupture caused by blunt trauma.

A modified nonsurgical treatment of keloids: Cocktail therapy.

BACKGROUND: The high recurrence rate after nonsurgical treatment of keloid is a major challenge for clinicians. Although there are many existing treatment options, how to optimize and upgrade the existing options and make a reasonable combination of utilization is our concern. The aim of this study is to provide a comprehensive non-surgical treatment for keloid-cocktail therapy. METHODS: According to the different changes of keloid with treatment, the treatment was divided into four stages, and different treatment schemes were adopted for each stage. The incidence of side effects of keloid at each stage and the effective rate and cure rate 16 months after the end of treatment were analyzed. RESULTS: All patients completed this study on time, and were followed up 16 months after the end of treatment, the treatment effective rate was 100%, and the cure rate was up to 92.8%. CONCLUSION: Cocktail therapy can achieve a higher cure rate of keloid, and is worthy of clinical promotion.

"A New Injection Method of Nerve Block Combined with Local Infiltration Anesthesia for Relieving Pain of Horizontal Neck Lines Injection".

SUMMARY: Filler injection is one of the effective methods for the treatment of horizontal neck lines, but the pain caused by injection has become a huge burden for many patients both physically and mentally. Topical anesthesia and local refrigeration are common methods to relieve the pain of injection, but each has its disadvantages. The transverse cervical nerve is the main innervating nerve for pain sensation in the anterior skin of the neck. In this study, we performed nerve block anesthesia and local infiltration anesthesia on one side of the horizontal neck lines and applied topical anesthesia cream on the other side of the neck among 100 patients. The results showed that the pain patients suffered under nerve block anesthesia and local infiltration anesthesia was reduced by 81% compared with that of patients using the topical anesthesia on their neck lines. And such anesthetic technique had multiple benefits, for example, it won't affect surgeon's judgment on patient's neck line shape and helps shorten the treatment time for patients. Therefore, it can be used as a new method to relieve the pain of patients undergoing horizontal neck line injection.

Effect of Mechanical Tension on the Long-Chain Noncoding RNA Expression Profile of Human Skin Regeneration.

This study investigates the potential gene regulation of long-chain noncoding RNAs (lncRNAs) during skin regeneration by analyzing the changes in the lncRNA expression profile during skin regeneration under mechanical tension. Through the effect of mechanical tension on human skin tissue, the authors observed that after the accelerated differentiation and proliferation of skin epidermal cells, the lncRNA expression profile was compared with that of normal epidermal cells, and differential expression of lncRNA in skin tissue was found. Fifty-three lncRNAs were differentially expressed between the experimental and control groups, and compared with the control group, 22 lncRNAs were upregulated and 31 lncRNAs were downregulated in the experimental group. In addition, through the annotation of the functions of gene ontology and kyoto encyclopedia of genes and genomes, it was further clarified that the main signaling pathway of lncRNAs in the process of skin tissue expansion is involved in the regulation of skin tissue regeneration, and the regulatory network of lncRNAs and microRNAs was established. The results of this study will provide a theoretical basis for the mechanism of lncRNA regulation of skin regeneration, and changes in the lncRNA expression profile can also provide clues for the study of the biological regulation mechanism of skin regeneration.

Surgical Correction of the Deformity After Orbicularis Oculi Muscle Rupture: A Case Report.

Facial contusion may be accompanied by inconspicuous structural damage of the underlying muscular tissue, leading to unnatural expressions. Surgery can be a choice to correct this dynamic deformity. This case report describes a rare case of orbicularis oculi muscle rupture following blunt injury. Cosmetic improvement was achieved with the surgical restoration of the torn muscle. The etiology of this phenomenon is also discussed.

Clinical Observation of Microplasma Radiofrequency Technology Combined With Glucocorticoid Injection in the Treatment of Hundreds of Cases of Hypertrophic Scar After Early Deep Burn and Scald.

BACKGROUND: To investigate the clinical efficacy and safety of microplasma radiofrequency technology combined with glucocorticoid injection in the treatment of hypertrophic scarring after early deep burns and scalding. METHODS: A total of 150 patients with hypertrophic scars after early deep burns from June 2018 to June 2021 were randomly divided into 3 groups, with 50 cases in each group. The patients were treated with compound betamethasone injection (Group A), microplasma radiofrequency technique (Group B), and compound betamethasone injection combined with microplasma radiofrequency technology (Group C). Each course of treatment included 5 standard treatments, and they were performed 6 weeks apart. Each patient was analyzed using the Vancouver scar scale and visual analogy scale after each treatment. The results were compared over time and across groups using repeated measurement analysis of variance. RESULTS: A total of 138 patients in these 3 groups completed this study. As treatment continued, the Vancouver scar scale value of Group C decreased more rapidly than that of Group A and Group B, and the difference was statistically significant ( P <0.05). In the improvement of scar pain and itching, there was little difference between Group C and Group A ( P >0.05), but both were better than Group B, and the difference was statistically significant ( P <0.05). Regarding the incidence of adverse reactions, there was little difference between Group C and Group B ( P >0.05), but the incidence of adverse reactions was lower than that of Group A, and the difference was statistically significant ( P <0.05). CONCLUSION: Microplasma radiofrequency combined with glucocorticoid injection in the treatment of hypertrophic scarring after early deep burns is effective, safe, and has a low incidence of adverse reactions, and it merits clinical promotion.

Contour first-retrospective study of an algorithmic approach of auricular keloids.

BACKGROUND: Auricular keloids are difficult to treat, and recurrent keloids are more aggressive and more likely to develop aural deformities. Surgical excision, injections, or radiotherapy alone have high recurrence rates. An algorithmic approach of auricular keloid remains to be explored. AIMS: To investigate the sequential treatment protocol for the treatment of auricle keloids to maintain auricle morphology and reduce the postoperative recurrence rate. PATIENTS/METHODS: A retrospective analysis of 42 patients who attended the scar minimally invasive treatment center of the Hospital of Plastic Surgery, Chinese Academy of Medical Sciences for serial treatment from January 2019 to June 2021. According to the size and involvement of the keloid, the core excision of the scar was excised under the condition of ensuring the priority of the auricular contour, and the scar flap was repaired to reconstruct the auricular appearance, and electron beam treatment was performed within 24 h after the operation, ray energy: 6-7 MeV, dose: Dt18Gy/2f; regular trimethoprim combined with 5-Fu injection treatment and the application of silicone ear clips for local compression treatment were performed 1 month after the operation. RESULTS: Thirty-five patients were followed up from 12 to 40 months after surgery, and three of them showed a tendency of recurrence, and early local treatment with trimethoprim and 5-Fu injection achieved favorable results. CONCLUSION: A standardized and sequential treatment plan for keloids with different morphology and anatomical locations can achieve remodeling of the auricular morphology and maintain long-term results.

Unilateral Double Eyelid Formation after Botulinum Toxin A Injection: A Case Report.

Botulinum toxin injection has been widely used for facial rejuvenation, with high rates of efficacy and patient satisfaction. In this article, we describe a reproducible phenomenon of unilateral double eyelid formation with the treatment of upper facial rhytides using botulinum toxin. A 38-year-old man was given onabotulinum toxin A injections in the frontal stria and glabellar lines. The procedure was repeated after 6 months. Unilateral double eyelids were noted twice on the right side about 7 days after each injection. The maintenance time for each procedure was about 1 month. The rhytides improved about 3 days after each injection and were maintained for about 4 months. No adverse effects were observed. This rare phenomenon could be due to the compensatory increased strength of the levator palpebrae superioris muscle and the anatomical structure of the patient's right eyelid.

Treatment of nasal depressed scars using micro-plasma radiofrequency technology combined with subcision.

BACKGROUND: The nose is located in the middle of the face; therefore, nasal scarring will bring a significant psychological impact on patients. Although there are many treatment methods for depressed scars, these methods have varying degrees of efficacy and all carry certain adverse effects. A better treatment method is urgent to be found. In this study, the effect of micro-plasma radiofrequency technology combined with subcision to treat nasal depressed scars is evaluated. METHODS: 18 Chinese patients with nasal depressed scars participated in this study. All patients received one session of micro-plasma radiofrequency treatment first. 2 months later, subcision combined with micro-plasma radiofrequency technology was performed on them at 6-month intervals, and a total of 2 sessions of combined treatment were performed. Goodman and Baron Scale was used to evaluate nasal scars before treatment and 6 months after the final session. RESULTS: All 18 patients in this study had Grade 4 nasal scars before treatment. 6 months after the end of treatment, 13 patients (72.2%) showed excellent or near total improvement, and 5 patients (27.8%) showed marked improvement. No adverse side effects were observed during treatment. Patient self-evaluation indicated that all patients were satisfied with the cosmetic outcomes. CONCLUSIONS: In this study, we explored a new treatment method for nasal depressed scars. We used micro-plasma radiofrequency technology combined with subcision to treat nasal depressed scars and obtained relatively satisfactory results with no adverse effects.

Inhibition of microRNA-21-5p reduces keloid fibroblast autophagy and migration by targeting PTEN after electron beam irradiation.

Electron beam (EB) irradiation is useful to reduce the recurrence of keloids; however, the underlying mechanism remains unknown. MicroRNA-21 (miR-21), which regulates autophagy during cancer radiation therapy, was identified as a potential therapeutic target for keloids. Here, we investigate the regulatory mechanism(s) of miR-21-5p on keloid fibroblast autophagy and migration after EB irradiation. The microRNA expression profile of the keloid dermis was examined by performing a microRNA microarray. Levels of LC3B and Beclin-1 were detected by immunohistochemical and western blot analysis in the keloid dermis and fibroblasts. Autophagy and apoptosis were tested in keloid fibroblasts after EB irradiation or transfection with an miR-21-5p inhibitor using electron microscopy, a Cyto-ID Green Autophagy Detection Kit, and an Annexin V PE Apoptosis Detection Kit. Migration was analyzed by an in vitro scratch-wound healing assay. Mechanistic tests were performed using small interfering RNAs to phosphatase and tensin homolog (siPTEN). Levels of miR-21-5p, PTEN, programmed cell death 4 (PDCD4), p-AKT, and apoptosis- and autophagy-associated genes were examined by qRT-PCR and western blotting. LC3B expression and migration ability were enhanced in fibroblasts and the keloid margin dermis compared with those in the adjacent normal skin. Both EB irradiation and an miR-21-5p inhibitor reduced keloid fibroblast autophagy, which was accompanied by decreased expression of miR-21-5p, p-AKT, and LC3B-II and increased expression of PTEN, PDCD4, and apoptosis-related genes. MiR-21-5p downregulation inhibited migration and suppressed LC3B expression and this was reversed by PTEN reduction. In conclusion, with increasing apoptosis, EB irradiation inhibits autophagy in keloid fibroblasts by reducing miR-21-5p, which regulates migration and LC3B expression via PTEN/AKT signaling. These data suggest a potential mechanism wherein miR-21-5p inhibition regulates autophagy and migration in EB-irradiated keloid fibroblasts, effectively preventing local invasion and recurrence. Therefore, miR-21-5p could be a new therapeutic target, to replace EB irradiation, and control keloid relapse.

MiR-21-5p Links Epithelial-Mesenchymal Transition Phenotype with Stem-Like Cell Signatures via AKT Signaling in Keloid Keratinocytes.

Keloid is the abnormal wound healing puzzled by the aggressive growth and high recurrence rate due to its unrevealed key pathogenic mechanism. MicroRNAs contribute to a series of biological processes including epithelial-mesenchymal transition (EMT) and cells stemness involved in fibrotic disease. Here, using microRNAs microarray analysis we found mir-21-5p was significantly up-regulated in keloid epidermis. To investigate the role of miR-21-5p in keloid pathogenesis, we transfected miR-21-5p mimic or inhibitor in keloid keratinocytes and examined the abilities of cell proliferation, apoptosis, migration and invasion, the expressions of EMT-related markers vimentin and E-cadherin and stem-like cells-associated markers CD44 and ALDH1, and the involvement of PTEN and the signaling of AKT and ERK. Our results demonstrated that up-regulation or knockdown of miR-21-5p significantly increased or decreased the migration, invasion and sphere-forming abilities of keloid keratinocytes, and the phenotype of EMT and cells stemness were enhanced or reduced as well. Furthermore, PTEN and p-AKT were shown to participate in the regulation of miR-21-5p on EMT phenotypes and stemness signatures of keloid keratinocytes, which might account for the invasion and recurrence of keloids. This molecular mechanism of miR-21-5p on keloid keratinocytes linked EMT with cells stemness and implicated novel therapeutic targets for keloids.

[In vitro study of TGF-ß1-induced epithelial-mesenchymal transition of keloid epithelial cells].

OBJECTIVE: To construct and characterize the TGF-ß1, induced epithelial-mesenchymal transition (EMT) model of keloid epithelial cells in vitro, and to investigate the expression of epithelial stem cells related surface markers in keloid epithelial cells during EMT induction. METHODS: The epithelial cells from 3 keloid samples of ears were cultured in vitro and induced by transforming growth factor betal (TGF-ß1, 1 ng/ml) for 5 days, which was the experimental group, the same cells untreated were considered as the negative control group. The expressions of EMT-associated markers and regulative genes were detected using immunofluorescence staining, real-time PCR and western blot analysis. Then the surface markers of epithelial stem cells were detected using real-time PCR. Statistical significance was determined using Independent-Samples t Test, a p value less than 0. 05 was considered statistically significant. RESULTS: The mRNA expression of transcription factor snail2 and mesenchymal-specific marker vimentin increased significantly in TGF-ß1, induced keloid epithelial cells (P < 0. 05), in which snail2 increasing from 0. 91 ± 0. 23 to 1. 69 ± 0. 10, and vimentin from 5. 86 ± 2. 07 to 24. 29 ± 5. 39. Whereas the mRNA expression of epithelial-specific marker E-cadherin decreased from 1. 06 ± 0. 19 to 0. 65 ± 0. 09. The mRNA expression of CD29 and Lgr6, two surface markers of epithelial stem cells, significantly increased after induction of the TGF-ß1, (P < 0. 05), from 0. 55 ± 0. 14 and 1. 61 ± 0. 31 to 1. 19 ± 0. 12 and 3. 84 t 0. 62 respectively. In induced cells, the immunofluorescence results showed staining of E- cadherin became faint, but the number of positive staining cells of vimentin increased. Western blot confirmed the protein expression of E-cadherin weakened, and the vimentin and p-Smad3 enhanced (P < 0. 05). CONCLUSIONS: TGF-ß1, initiated EMT in keloid epithelial cells by inducing the up-regulation of snail2, and TGF-ß1,/Smad3 signaling pathway was involved in EMT. EMT could change the phenotype of epithelial stem cells in keloid.

Epithelial-mesenchymal transition in keloid tissues and TGF-ß1-induced hair follicle outer root sheath keratinocytes.

Keloid is a skin fibrotic disease with the characteristics of recurrence and invasion, its pathogenesis still remains unrevealed. The epithelial-mesenchymal transition (EMT) is critical for wound healing, fibrosis, recurrence, and invasion of cancer. We sought to investigate the EMT in keloid and the mechanism through which the EMT regulates keloid formation. In keloid tissues, the expressions of EMT-associated markers and transforming growth factor (TGF)-ß1/Smad3 signaling were examined by immunohistochemistry. In the keloid epidermis and dermal tissue, the expressions of genes related to the regulation of skin homeostasis, fibroblast growth factor receptor 2 (FGFR2) and p63, were analyzed using quantitative real-time polymerase chain reaction. The results showed that accompanying the loss of the epithelial marker E-cadherin and the gain of the mesenchymal markers fibroblast-specific protein 1 (FSP1) and vimentin in epithelial cells from epidermis and skin appendages, and in endothelial cells from dermal microvessels, enhanced TGF-ß1 expression and Smad3 phosphorylation were noted in keloid tissues. Moreover, alternative splicing of the FGFR2 gene switched the predominantly expressed isoform from FGFR2-IIIb to -IIIc, concomitant with the decreased expression of ΔNp63 and TAp63, which changes might partially account for abnormal epidermis and appendages in keloids. In addition, we found that TGF-ß1-induced hair follicle outer root sheath keratinocytes (ORSKs) and normal skin epithelial cells underwent EMT in vitro with ORSKs exhibiting more obvious EMT changes and more similar expression profiles for EMT-associated and skin homeostasis-related genes as in keloid tissues, suggesting that ORSKs might play crucial roles in the EMT in keloids. Our study provided insights into the molecular mechanisms mediating the EMT pathogenesis of keloids.

The use of micro-plasma radiofrequency technology in secondary skin graft contraction: 2 case reports.

Secondary skin graft contraction leading to cosmetic deformity remains a great challenge. These two case reports present serious skin graft contraction and the treatment with micro-plasma radiofrequency technology. Two patients presented with complaints of post-burn depigmentation on the forehead and the hand, respectively, and received dermabrasion and thin split-thickness skin grafting. Then, many localized contraction lesions occurred after 4 weeks. The treatment selected was non-surgical removal using micro-plasma radiofrequency technology with the following energy parameters: a roller tip at 80 watts, three passes in different directions. No complications were observed. The contracted skin was ablated without affecting the pigment distribution. The consequents were that the color, appearance, and texture of the grafted skin matched the adjacent skin well and had better patient acceptance.

Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology.

Management of facial post-burn hyperpigmentation is a common and challenging problem for dermatologists and plastic surgeons. The recent development of micro-plasma radiofrequency technology, which allows precise and rapid treatment with controlled thermal injury, can be an effective treatment of post-burn hyperpigmentation. This study aimed to evaluate the effectiveness and complications of micro-plasma radiofrequency treatment of post-burn hyperpigmentation. The study included 35 patients with Fitzpatrick skin type III or IV and facial post-burn hyperpigmentation. Patients received three to five treatments at 8-week intervals. A roller tip was used with the power setting at 60-90 W, and 3-4 passes were made in different directions. The degree of improvement and complications were recorded. Improvement of hyperpigmentation was evaluated by patient self-assessment and by plastic surgeons who compared digital photographs taken before treatment and 2 months after the last treatment. The results showed that post-burn hyperpigmentation responded favorably to micro-plasma radiofrequency treatment with very few complications. The average pain score using a visual analog scale from 0 to 10 was 6.7 ± 0.7. After a series of treatments, 32 of the 35 patients had achieved a >51% improvement of their hyperpigmentation, and 3 patients had achieved a fair improvement. The mean score for improvement of hyperpigmentation was 4.28. Patient self-evaluations indicated good satisfaction with the cosmetic outcomes, and some softening of the scars. Micro-plasma radiofrequency technology is appropriate, effective, and safe for the treatment of facial post-burn hyperpigmentation, and provides a promising noninvasive treatment for superficial facial injuries.