New research advances in hypertrophic scar formation, prevention and treatment / 中华预防医学杂志

Scarring, naturally induced by fibroblasts(Fb) during wound healing, is an essential process in response to repair damaged tissue. Excessive Fb proliferation which produces the excessive collagen deposition, including increased extracellular matrix synthesis or insufficient decomposition, typically contributes to hypertrophic scar(HS) formation. Although exact mechanisms of HS are not yet fully understood, it is generally believed that dysfunction of Fb and regulation of signal pathways play an important role in HS formation. Biologically, Fb function is affected by various factors such as cytokines, extracellular matrix and itself. In addition, modifications of miRNA, ceRNA, lncRNA, peptides and histones participate in HS formation by affecting the biological function of Fb. Despite the clinical importance, very few therapeutic modalities are available to prevent HS. To achieve this, a deeper characterization of Fb is required to identify mechanisms of HS. To the aspect of HS prevention and treatment, we review recent findings, concentrating on Fb function and collagen secretion. The objective of this article is to frame the current understanding, gain the deeper insights into Fb function, and provide the more comprehensive cognition and perspective for prevention and treatment of HS.

Research advances on the role and mechanism of microRNA in hypertrophic scar / 中华烧伤杂志

Hypertrophic scar (HS) affects the function and beauty of patients, and brings a heavy psychological burden to patients. However, the specific pathogenesis mechanism of HS in molecular biology level is not yet clear, and this disease is still one of the clinical diseases difficult to prevent and cure. MicroRNA (miR) is a family of single-stranded endogenous noncoding RNAs that can regulate gene expression. The abnormal transcription of miR in hypertrophic scar fibroblasts can affect the transduction and expression of downstream signal pathway or protein, and the exploration of miR and its downstream signal pathway and protein helps deeply understand the occurrence and development mechanism of scar hyperplasia. This article summarized and analyzed how miR and multiple signal pathways involve in the formation and development of HS in recent years, and further outlined the interaction between miR and target genes in HS.

A prospective study on the development and application verification of the quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology / 中华烧伤杂志

Objective: To develop a quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology, and to verify its accuracy and feasibility in clinical application. Methods: The method of prospective observational study was adopted. From April 2019 to January 2022, 59 patients with pathological scars (totally 107 scars) who met the inclusion criteria were admitted to the First Medical Center of Chinese PLA General Hospital, including 27 males and 32 females, aged 33 (26, 44) years. Based on photo modeling technology, a software for measuring three-dimensional morphological parameters of pathological scars was developed with functions of collecting patients' basic information, and scar photography, three-dimensional reconstruction, browsing the models, and generating reports. This software and the clinical routine methods (vernier calipers, color Doppler ultrasonic diagnostic equipment, and elastomeric impression water injection method measurement) were used to measure the longest length, maximum thickness, and volume of scars, respectively. For scars with successful modelling, the number, distribution of scars, number of patients, and the longest length, maximum thickness, and volume of scars measured by both the software and clinical routine methods were collected. For scars with failed modelling, the number, distribution, type of scars, and the number of patients were collected. The correlation and consistency of the software and clinical routine methods in measuring the longest length, maximum thickness, and volume of scars were analyzed by unital linear regression analysis and the Bland-Altman method, respectively, and the intraclass correlation coefficients (ICCs), mean absolute error (MAE), and mean absolute percentage error (MAPE) were calculated. Results: A total of 102 scars from 54 patients were successfully modeled, which located in the chest (43 scars), in the shoulder and back (27 scars), in the limb (12 scars), in the face and neck (9 scars), in the auricle (6 scars), and in the abdomen (5 scars). The longest length, maximum thickness, and volume measured by the software and clinical routine methods were 3.61 (2.13, 5.19) and 3.53 (2.02, 5.11) cm, 0.45 (0.28, 0.70) and 0.43 (0.24, 0.72) cm, 1.17 (0.43, 3.57) and 0.96 (0.36, 3.26) mL. The 5 hypertrophic scars and auricular keloids from 5 patients were unsuccessfully modeled. The longest length, maximum thickness, and volume measured by the software and clinical routine methods showed obvious linear correlation (with r values of 0.985, 0.917, and 0.998, P<0.05). The ICCs of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.993, 0.958, and 0.999 (with 95% confidence intervals of 0.989-0.995, 0.938-0.971, and 0.998-0.999, respectively). The longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods had good consistency. The Bland-Altman method showed that 3.92% (4/102), 7.84% (8/102), and 8.82% (9/102) of the scars with the longest length, maximum thickness, and volume respectively were outside the 95% consistency limit. Within the 95% consistency limit, 2.04% (2/98) scars had the longest length error of more than 0.5 cm, 1.06% (1/94) scars had the maximum thickness error of more than 0.2 cm, and 2.15% (2/93) scars had the volume error of more than 0.5 mL. The MAE and MAPE of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.21 cm, 0.10 cm, 0.24 mL, and 5.75%, 21.21%, 24.80%, respectively. Conclusions: The quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology can realize the three-dimensional modeling and measurement of morphological parameters of most pathological scars. Its measurement results were in good consistency with those of clinical routine methods, and the errors were acceptable in clinic. This software can be used as an auxiliary method for clinical diagnosis and treatment of pathological scars.

Shikonin promotes hypertrophic scar repair by autophagy of hypertrophic scar-derived fibroblasts

Purpose: To investigate the Shikonin (SHI) induce autophagy of hypertrophic scar-derived fibroblasts (HSFs) and the mechanism of which in repairing hypertrophic scar. Methods: This study showed that SHI induced autophagy from HSFs and repaired skin scars through the AMPK/mTOR pathway. Alamar Blue and Sirius red were used to identify cell activity and collagen. Electron microscopy, label-free quantitative proteomic analysis, fluorescence and other methods were used to identify autophagy. The differences in the expression of autophagy and AMPK/mTOR pathway-related proteins after SHI treatment were quantitatively analyzed by Western blots. A quantitative real-time polymerase chain reaction assay was used to detect the expression of LC3, AMPK and ULK after adding chloroquine (CQ) autophagy inhibitor. Results: After treatment with SHI for 24 hours, it was found that the viability of HSFs was significantly reduced, the protein expression of LC3-II/LC3-I and Beclin1 increased, while the protein expression of P62 decreased. The expression of phosphorylated AMPK increased and expression of phosphorylated mTOR decreased. After the use of CQ, the cell autophagy caused by SHI was blocked. The key genes LC3 and P62 were then reexamined by immunohistochemistry using a porcine full-thickness burn hypertrophic scar model, and the results verified that SHI could induce autophagy in vivo. Conclusions: These findings suggested that SHI promoted autophagy of HSFs cells, and the potential mechanism may be related to the AMPK/mTOR signal pathway, which provided new insights for the treatment of hypertrophic scars.

Clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns / 中华烧伤杂志

Objective: To investigate the clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns. Methods: A retrospective observational study was used. From June 2017 to June 2019, 33 patients (24 males and 9 females, aged 8-50 years) who met the inclusion criteria with hypertrophic scars in non-functional sites outside the face after burns were treated in General Hospital of TISCO (the Sixth Hospital of Shanxi Medical University). All patients underwent scalp transplantation after perforation of retained split scar matrix in situ (with scar thinning area of 90-500 cm2), and then the vacuum sealing drainage was performed. The hematoma and infection of wounds were observed on the 7th day after operation. At the same time, the survival rate of skin grafting was observed and calculated. The flatness and thickness of the scar in the operative area were observed in 12 months after operation, and the itching and pain of the patients were recorded. Vancouver Scar Scale was used to score the scar of patients before operation and at 3, 6 and 12 months after operation. The healing time and hair growth of donor site were observed. Data were statistically analyzed with repeated analysis of variance, paired sample t test and bonferroni correction. Results: On the 7th day after operation, local subcutaneous hematoma appeared in the wound of 2 patients, which healed after dressing change; no infection occurred. On the 7th day after operation, the survival rate of skin grafting of patients was 94.6%-99.0%(96.8±1.2)%. Scar flatness was well, the thickness of scar was not significantly higher than that of normal skin in 12 months after operation, and the symptoms of itching pain of patients disappeared or significantly relieved. Vancouver Scar Scale scores of patients before operation and at 3, 6, and 12 months after operation were 12.1±2.8, 8.5±1.5, 7.6±1.6, 6.7±1.3, respectively, and the scores of 3, 6, and 12 months after operation were all significantly lower than that before operation (with t values of 4.48, 4.06, and 3.97, respectively, P<0.01). All the donor sites of the head healed well in 4-7 days after operation. By 3-6 months after operation, all patients had good hair growth in the donor site and achieved no scar healing. Conclusions: The treatment of hypertrophic scar in non-functional sites outside the face after burns by in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage can effectively improve the appearance of hypertrophic scar in non-functional areas after burn and reduce its degree of hyperplasia, with scar-free donor site healing.

A prospective randomized controlled study on the effects of compound analgesia in ultra-pulsed fractional carbon dioxide laser treatment of post-burn hypertrophic scars in children / 中华烧伤杂志

Objective: To investigate the effects of compound analgesia on ultra-pulsed fractional carbon dioxide laser (UFCL) treatment of post-burn hypertrophic s in children. Methods: A prospective randomized controlled study was conducted. From April 2018 to March 2020, 169 pediatric patients with post-burn hypertrophic s admitted to the First Affiliated Hospital of Air Force Medical University were randomly divided into general anesthesia alone group (39 cases, 19 males and 20 females, aged 35 (21, 48) months), general anesthesia+lidocaine group (41 cases, 23 males and 18 females, aged 42 (22, 68) months), general anesthesia+ibuprofen suppository group (41 cases, 25 males and 16 females, aged 38 (26, 52) months), and three-drug combination group with general anesthesia + lidocaine+ibuprofen suppository (48 cases, 25 males and 23 females, aged 42 (25, 60) months), and the pediatric patients in each group were treated with corresponding analgesic regimens when UFCL was used to treat s, and the pediatric patients were given comprehensive care throughout the treatment process. The pain degree of pediatric patients scar was evaluated by facial expression,legs,activity,cry,and consolability (FLACC) of children's pain behavior scale at 0 (immediately), 1, 2, and 4 h after awakening from the first anesthesia, respectively. At 4 h after awakening from the first anesthesia of postoperative pain assessment, the self-made analgesia satisfaction questionnaire was used to evaluate the satisfaction for the analgesic effect of the pediatric patients or their families, and the satisfaction rate was calculated. Within 2 h after the first operation, the occurrences of adverse reactions of the pediatric patients, such as nausea and vomiting, headache, dizziness, drowsiness, etc, were observed and recorded. Before the first treatment and 1 month after the last treatment, the Vancouver scar scale (VSS) was used to evaluate the pediatric patients scar, and the difference value between the two was calculated. Data were statistically analyzed with least significant difference test, Kruskal-Wallis H test, chi-square test and Fisher's exact probability test. Results: At 0 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group (P<0.01). The FLACC scores of the pediatric patients in anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than that in general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 1 and 2 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were both significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 4 h after awakening from the first anesthesia, the FLACC scores of the pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01). At 4 h after awakening from the first anesthesia, the satisfactions rate with the analgesic effect in the four groups of pediatric patients or their families were 79.49% (31/39), 85.37% (35/41), 87.80% (36/41), and 97.92% (47/48), respectively. The satisfaction rate of the pediatric patients in three-drug combination group was significantly higher than those in general anesthesia alone group, general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group. Within 2 h after the first operation, there was no significant difference in the overall comparison of adverse reactions such as nausea and vomiting, headache, dizziness, and drowsiness of pediatric patients among the 4 groups (P>0.05). The VSS scores of pediatric patients before the first treatment, 1 month after the last treatment, and and the difference value between the two in the 4 groups were not significantly different (P>0.05). Conclusions: Three-drug combination for analgesia has a good effect in the treatment of hypertrophic scars after burn in pediatric patients with UFCL. Pediatric patients or their families are highly satisfied with the effect, and the treatment effect and incidence of adverse reactions are similar to other analgesic regimens, so it is recommended to be promoted in clinical practice.

A case of chronic refractory wound in the abdomen caused by residual foreign body / 中华烧伤杂志

A 59-year-old male patient with local sinus tract formation due to residual foreign body was admitted to the Second Affiliated Hospital of Zhejiang University College of Medicine on December 17, 2018. The examination showed that the residual foreign body was the component of a sticky cloth implanted when the patient underwent appendectomy 27 years ago. Hypertrophic scar developed at the right-lower abdominal incision for appendectomy 23 years ago and the secondary infection after cicatrectomy resulted in non-healing of the wound. The chronic refractory wound healed completely after surgical treatment in our hospital after this admission. The postoperative pathological examination revealed local inflammatory granuloma. This case suggests that chronic refractory wound is likely to form when secondary infection occurs following the surgical procedure near the implant, and aggressive surgery is an effective way to solve this problem.

Aspirin inhibits the growth of hypertrophic scar in rabbit ears via regulating Wnt/β-catenin signal pathway / 中南大学学报(医学版)

OBJECTIVES@#Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism.@*METHODS@#The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score.@*RESULTS@#All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (P<0.05). Immunohistochemistry showed that the expression of β-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (P<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all P>0.05).@*CONCLUSIONS@#Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/β-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.

Regulatory effects and signaling mechanism of sodium ferulate on the proliferation and apoptosis of human skin hypertrophic scar fibroblasts / 中华烧伤杂志

Objective: To investigate the regulatory effects and signaling mechanism of sodium ferulate on the proliferation and apoptosis of human skin hypertrophic scar fibroblasts (HSFbs). Methods: The experimental research methods were used. The 4th-6th passage of HSFbs from human skin were used for the following experiments. HSFbs were co-cultured with sodium ferulate at final mass concentrations of 1, 1×10-1, 1×10-2, 1×10-3, 1×10-4, 1×10-5, and 1×10-6 mg/mL for 48 hours, and methyl thiazolyl tetrazolium method was used to determine the cell absorbance values and linear regression was used to analyze the half lethal concentration (LC50) of sodium ferulate (n=6). HSFbs were co-cultured with sodium ferulate at final mass concentrations of 0.1, 0.2, 0.3, and 0.4 mg/mL for 24, 48, 72, and 96 hours, and methyl thiazolyl tetrazolium method was used to determine the cell absorbance values and the cell proliferation inhibition rate was calculated (n=3). According to the random number table, the cells were divided into 0.300 mg/mL sodium ferulate group, 0.030 mg/mL sodium ferulate group, 0.003 mg/mL sodium ferulate group treated with sodium ferulate at corresponding final mass concentrations, and negative control group without any treatment. After 72 hours of culture, the cell absorbance values were determined by methyl thiazolyl tetrazolium method (n=5), the microscopic morphology of cells was observed by transmission electron microscope (n=3), the cell apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay and the apoptosis index was calculated (n=4), the protein expressions of B lymphocystoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cysteine aspartic acid specific protease-3 (caspase-3) were determined by immunohistochemistry (n=4), and the protein expressions of transformed growth factor β1 (TGF-β1), phosphorylated Smad2/3, phosphorylated Smad4, and phosphorylated Smad7 were detected by Western blotting (n=4). Data were statistically analyzed with one-way analysis of variance and Dunnett test. Results: The LC50 of sodium ferulate was 0.307 5 mg/mL. After being cultured for 24-96 hours, the cell proliferation inhibition rates of cells treated with sodium ferulate at four different mass concentrations tended to increase at first but decrease later, which reached the highest after 72 hours of culture, so 72 hours was chosen as the processing time for the subsequent experiments. After 72 hours of culture, the cell absorbance values in 0.003 mg/mL sodium ferulate group, 0.030 mg/mL sodium ferulate group, and 0.300 mg/mL sodium ferulate group were 0.57±0.06, 0.53±0.04, 0.45±0.05, respectively, which were significantly lower than 0.69±0.06 in negative control group (P<0.01). After 72 hours of culture, compared with those in negative control group, the cells in the three groups treated with sodium ferulate showed varying degrees of nuclear pyknosis, fracture, or lysis, and chromatin loss. In the cytoplasm, mitochondria were swollen, the rough endoplasmic reticulum was expanded, and local vacuolation gradually appeared. After 72 hours of culture, compared with that in negative control group, the apoptosis indexes of cells were increased significantly in 0.003 mg/mL sodium ferulate group, 0.030 mg/mL sodium ferulate group, and 0.300 mg/mL sodium ferulate group (P<0.05 or P<0.01). After 72 hours of culture, compared with those in negative control group, the protein expressions of Bcl-2 of cells in 0.300 mg/mL sodium ferulate group was significantly decreased (P<0.01), the protein expressions of Bax of cells in 0.030 mg/mL sodium ferulate group and 0.300 mg/mL sodium ferulate group were significantly increased (P<0.05), and the protein expression of caspase-3 of cells in 0.300 mg/mL sodium ferulate group was significantly increased (P<0.01). After 72 hours of culture, compared with those in negative control group, the protein expression levels of TGF-β1, phosphorylated Smad2/3, and phosphorylated Smad4 of cells in 0.030 mg/mL sodium ferulate group and 0.300 mg/mL sodium ferulate group were significantly decreased (P<0.05 or P<0.01), and the protein expression levels of phosphorylated Smad7 of cells in 0.003 mg/mL sodium ferulate group, 0.030 mg/mL sodium ferulate group, and 0.300 mg/mL sodium ferulate group were significantly increased (P<0.01). Conclusions: Sodium ferulate can inhibit the proliferation of HSFbs of human skin and promote the apoptosis of HSFbs of human skin by blocking the expression of key proteins on the TGF-β/Smad signaling pathway and synergistically activating the mitochon- drial apoptosis pathway.

Tacrolimus action pathways in an ointment base for hypertrophic scar prevention in a rabbit ear model

Abstract Background: Tacrolimus is used to prevent unaesthetic scars due to its action on fibroblast activity and collagen production modulation. Objectives: To evaluate the action pathways, from the histopathological point of view and in cytokine control, of tacrolimus ointment in the prevention of hypertrophic scars. Methods: Twenty-two rabbits were submitted to the excision of two 1-cm fragments in each ear, including the perichondrium. The right ear received 0.1% and 0.03% tacrolimus in ointment base twice a day in the upper wound and in the lower wound respectively. The left ear, used as the control, was treated with petrolatum. After 30 days, collagen fibers were evaluated using special staining, and immunohistochemistry analyses for smooth muscle actin, TGF-β and VEGF were performed. Results: The wounds treated with 0.1% tacrolimus showed weak labeling and a lower percentage of labeling for smooth muscle actin, a higher proportion of mucin absence, weak staining, fine and organized fibers for Gomori's Trichrome, strong staining and organized fibers for Verhoeff when compared to controls. The wounds treated with 0.03% tacrolimus showed weak labeling for smooth muscle actin, a higher proportion of mucin absence, strong staining for Verhoeff when compared to the controls. There was absence of TGF-β and low VEGF expression. Study limitations: The analysis was performed by a single pathologist. Second-harmonic imaging microscopy was performed in 2 sample areas of the scar. Conclusions: Both drug concentrations were effective in suppressing TGF-β and smooth muscle actin, reducing mucin, improving the quality of collagen fibers, and the density of elastic fibers, but only the higher concentration influenced elastic fiber organization.

The effect of proliferative hypertrophic scars on determining treatment options for preventing recurrence of vesicourethral anastomotic stenosis after radical prostatectomy: a single-center cross-sectional study

ABSTRACT BACKGROUND: Vesicourethral anastomotic stenosis (VUAS) following retropubic radical prostatectomy (RRP) significantly worsens quality of life. OBJECTIVES: To investigate the relationship between proliferative hypertrophic scar formation and VUAS, and predict more appropriate surgical intervention for preventing recurrent VUAS. DESIGN AND SETTING: Retrospective cross-sectional single-center study on data covering January 2009 to December 2019. METHODS: Among 573 male patients who underwent RRP due to prostate cancer, 80 with VUAS were included. They were divided into two groups according to VUAS treatment method: dilatation using Amplatz renal dilators (39 patients); or endoscopic bladder neck incision/resection (41 patients). The Vancouver scar scale (VSS) was used to evaluate the characteristics of scars that occurred for any reason before development of VUAS. RESULTS: Over a median follow-up of 72 months (range 12-105) after RRP, 17 patients (21.3%) had recurrence of VUAS. Although the treatment success rates were similar (79.5% versus 78.0%; P = 0.875), receiver operating characteristic (ROC) curve analysis indicated that dilatation using Amplatz dilators rather than endoscopic bladder neck incision/resection in patients with VSS scores 4, 5 and 6 may significantly reduce VUAS recurrence. A strong positive relationship was observed between VSS and total number of VUAS occurrences (r: 0.689; P < 0.001). VSS score (odds ratio, OR: 5.380; P < 0.001) and time until occurrence of VUAS (OR: 1.628; P = 0.008) were the most significant predictors for VUAS recurrence. CONCLUSIONS: VSS score can be used as a prediction tool for choosing more appropriate surgical intervention, for preventing recurrent VUAS.

Reintroducción de la circuncisión como una técnica quirúrgica reconstructiva / Reintroduction of Circumcision as a Technique Reconstructive Surgical

La circuncisión es una cirugía practicada frecuentemente en urología. Sin tener en cuenta los principios básicos de la cirugía reconstructiva, puede generar procesos de cicatrización anómalos, con resultados estéticos y funcionales inadecuados, fimosis secundaria, cicatrización hipertrófica, queloide o "pene enterrado." El objetivo de este video es recordar la importancia de operar con las directrices de una cirugía reconstructiva, resaltando el cuidado de los tejidos y el uso de suturas de bajo calibre, para prevenir complicaciones y resultados insatisfactorios, resaltando la preservación de las zonas postuladas por Firlit. Se sospecha que las complicaciones de este procedimiento son subestimadas por los especialistas. El manejo cuidadoso de los tejidos, el uso de suturas de bajo calibre y los puntos subcuticulares con poca tensión, son medios para optimizar el proceso de cicatrización, evitando la isquemia y las cicatrices hipertróficas, basados en el fundamento de que esta es una cirugía no solo funcional, sino reconstructiva y estética. La circuncisión es un procedimiento que debe conservar la funcionalidad y estética del pene, por lo que debe ser realizado bajo las directrices de una cirugía

Circumcision is a frequently practiced surgical procedure in urology. Without considering the basic principles of reconstructive surgery, it can result in abnormal cicatrization processes, with inadequate aesthetic or functional results, secondary phimosis, hypertrophic or keloid scarring, or even "buried penis." The objective of this video is to remind the importance of operating with the principles of reconstructive surgery, highlighting the careful handling of tissues and the use of low-caliber sutures, to prevent complications and unsatisfactory results, preserving the areas postulated by Firlit. The complications of this procedure are suspected to be underestimated by specialists. Careful tissue management, the use of low-caliber sutures and subcuticular points with no tension are means to optimize the healing process, avoiding ischemia and hypertrophic scars, based on the fact that this is a surgery that is not only functional, but reconstructive and aesthetic as well. Circumcision is a procedure that must preserve the functionality and aesthetics of the penis and it must be performed under the principles of reconstructive surgery.

Emodin alleviates hypertrophic scar formation by suppressing macrophage polarization and inhibiting the Notch and TGF-β pathways in macrophages

Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-β pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-β, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-β pathways in macrophages.

Inhibition of Notch signaling pathway reduces angiogenesis in hypertrophic scar / 中南大学学报(医学版)

OBJECTIVES@#Hypertrophic scar (HS) is the most common pathological scar in clinical practice. During its formation, angiogenesis-related factors show dynamic expression. Modern studies have found that Notch signaling pathway has an extremely important role in maintaining the construction and remodeling of vascular endothelial cells and vascular network. The correlation between Notch signaling pathway and angiogenesis in hypertrophic scar has been rarely reported. This study aims to investigate correlation between Notch signaling pathway and the expression of angiogenic factors in a proliferative scar model.@*METHODS@#A total of 81 Sprague Dawley rats (SPF grade) were randomly assigned into a blank control group, a model group, and a blocker group. In the blocker group, a 2 cm diameter circular scald head was placed on the back of the rats for 10 s at 75 ℃ by using a constant temperature and pressure electrothermal scalding apparatus to form a rat deep II° burn model, and a hyperplastic scar model rat was obtained after natural healing of the wound skin (21 to 23 day epithelialization). A syringe was used to inject a needle from the normal skin around the scar at the 1st, 3rd, 5th, 7th, and 14th days after modeling. The γ-secretase inhibitor was injected locally at 2 mg/kg in a dilution of 0.1 mL at the base of the scar. The rats in the model group was injected with the same amount of saline after modeling; the rats in the blank control group was injected with the same amount of saline. Nine rats in each group was randomly killed by air embolization at the 21st, 28th, and 35th days, respectively. The protein expressions of collagen type I (COL-I) and collagen type III (COL-III) were detected by immunohistochemistry. The protein expressions of vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang1), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-2 (MMP-2) were detected by Western blotting.@*RESULTS@#Immunohistochemical results showed that, at the 21st,28th, and 35th days, the protein expressions of COL-I and COL-III in the model group were up-regulated compared with the blank control group (all @*CONCLUSIONS@#In the Sprague Dawley rat proliferative scar model, inhibition of Notch signaling pathway could attenuate the expressions of COL-I and COL-III, reduce traumatic scar proliferation, down-regulate the expressions of VEGF, Ang1, TGF-β1, and MMP-2, and inhibit angiogenesis. The expressions of angiogenesis-related factors appeare to be up-regulated during the formation of proliferative scar. When the Notch signaling pathway is inhibited, the up-regulated angiogenic factors show a decreasing trend and the proliferative scar is alleviated, which suggests that Notch signaling pathway may affect the formation of hyperplastic scar by regulating the expression of angiogenic factors.

Máscara termoplástica recubierta de silicona para el manejo de la cicatriz hipertrófica facial / Silicone coated thermoplastic mask for management of hypertrophic facial scars

Resumen Las quemaduras secundarias a agresión física con intención de desfigurar, torturar o incluso asesinar, se han convertido en un motivo de consulta común en el siglo XXI, siendo Bangladesh el país con la más alta incidencia en el mundo. Colombia es uno de los países con mayor incidencia a nivel de Latinoamérica. La mayoría de las lesiones ocurre en áreas expuestas como el rostro y se acompaña de graves secuelas físicas, estéticas y funcionales. Se realiza la presentación de caso de una paciente de 35 años con quemaduras de tercer grado en región frontal, periocular, malar bilateral, nasal, labial superior y pabellón auricular derecho, manejada con injertos de piel, quien posteriormente desarrolla cicatriz hipertrófica. Se describe el tratamiento con máscara termoplástica elaborada por los profesionales tratantes, con cubierta interna de silicona, fabricada sobre molde a medida y ajustada con bandas elásticas; integrando en un único dispositivo removible, cómodo y de bajo costo, diferentes alternativas terapéuticas que logran modular efectivamente el proceso de cicatrización y por su simplicidad favorecen la adherencia al tratamiento, la cual es indispensable para obtener resultados satisfactorios. MED.UIS.2020;33(3): 49-58

Abstract Burns secondary to physical aggression with the intention of disfiguring, torturing or even murdering, have become a common reason for consultation in the 21st century, with Bangladesh being the country with the highest incidence in the world. Colombia is one of the countries with the highest incidence in Latin America. Most injuries occur in exposed areas such as the face and are accompanied by serious physical, aesthetic and functional sequelae. We present the case of a 35-year-old patient with third degree burns in the frontal, periocular, bilateral malar, nasal, upper labial and right ear region, managed with skin grafts, who later developed a hypertrophic scar. The treatment with a thermoplastic mask made by the treating professionals is described, with an internal silicone cover, made on a custom mold and adjusted with elastic bands; integrating in a single removable, comfortable and low-cost device, different therapeutic alternatives that manage to effectively modulate the healing process and, due to their simplicity, favor adherence to treatment, which is essential to obtain satisfactory results. MED.UIS.2020;33(3): 49-58

Recidiva de cicatriz queloide en pacientes tratados con resección quirúrgica más radioterapia / Keloid scar recurrence in patients treated with surgical resection plus radiotherapy

INTRODUCCIÓN. El proceso de cicatrización puede derivar en anomalías, que afectan el aspecto estético y funcional de la zona afectada; la combinación de tratamientos ha permi-tido resultados favorables. OBJETIVOS. Describir los factores que se dan en las recidivas de cicatriz queloide en pacientes tratados con resección quirúrgica más radioterapia. MA-TERIALES Y MÉTODOS. Estudio observacional, descriptivo y retrospectivo. Población de 2 960 Historias Clínicas, se tomó muestra de 100. Criterios de inclusión: diagnóstico de cicatriz queloide, edad de 12 a 75 años, combinación de tratamiento quirúrgico y radiotera-pia. Criterios de exclusión: edades fuera del rango, tratamiento diferente, en la Unidad de Plástica y Reconstructiva del Hospital de Especialidades Carlos Andrade Marín durante el período enero 2013 a diciembre 2019. Los datos fueron tomados del sistema AS400, el análisis se realizó en el programa estadístico International Business Machines Statistical Package for the Social Sciences, versión 22. RESULTADOS. La localización frecuente fue en el pabellón auricular con 83% (83; 100), de estos el 57% (57; 100) fueron poste-rior a perforación; la recidiva se presentó en el 24% (24; 100) y la principal complicación en los pacientes fue Radiodermitis. DISCUSIÓN. La evidencia científica guardó relación con el estudio referente a técnica, sexo, localización del queloide, causa y complicación. CONCLUSIÓN. Se pudo describir los factores que se dieron en las recidivas de cicatriz queloide en pacientes tratados con resección quirúrgica más radioterapia.

INTRODUCTION. The healing process can lead to anomalies, which affect the aesthe-tic and functional appearance of the affected area; the combination of treatments have allowed favorable results. OBJECTIVES. Describe the factors that occur in keloid scar recurrences in patients treated with surgical resection plus radiotherapy. MATERIALS AND METHODS. Observational, descriptive and retrospective study. Population of 2 960 Clini-cal Histories, a sample of 100 was taken. Inclusion criteria: diagnosis of keloid scar, age 12 to 75 years, combination of surgical treatment and radiotherapy. Exclusion criteria: ages outside the range, different treatment, in the Plastic and Reconstructive Unit of the Carlos Andrade Marín Specialty Hospital during the period January 2013 to December 2019. The data were taken from the AS400 system, the analysis was carried out in the program Sta-tistical International Business Machines Statistical Package for the Social Sciences, ver-sion 22. RESULTS. The frequent location was in the auricle with 83% (83; 100), of these 57% (57; 100) were after perforation; recurrence occurred in 24% (24; 100) and the main complication in patients was Radiodermatitis. DISCUSSION. The scientific evidence was related to the study referring to technique, sex, location of the keloid, cause and compli-cation. CONCLUSION. It was possible to describe the factors that occurred in keloid scar recurrences in patients treated with surgical resection plus radiotherapy.

Presence of Type 1 Collagen Alpha-2 (COL1A2) (rs42524) Gene Polymorphism and Scar Tissue Formation in Different Areas of Head and Neck

Abstract Objective: To determine the effect type I collagen gene polymorphism alpha-2 (COL1A2) (rs42524) on the formation of scar tissue that is localized in the head and neck areas. Material and Methods: Sixty patients with scars in different areas of the head and neck were examined. The patients were divided into four subgroups, according to the types of scarring: G I: 15 patients with normotrophic scars; G ІІ: 15 patients with atrophic scars; G ІІІ: 15 patients with hypertrophic scars; and G IV: 15 patients with keloid scars. The age of patients ranged from 17 to 54 years. The single-nucleotide polymorphic site of the COL1A2 (rs42524) gene was detected by a polymerase chain reaction and subsequent analysis of restriction fragment lengths. Pearson's chi-squared test with Yates's correction and Fischer's exact test were used. Results: There were no significant changes between the control and basic groups (p=0.83) at analyzing the frequencies of G and C alleles. For the G allele, the calculation of odds ratio between the basic and control groups was 0.93 at 95% confidence interval (CI) (0.50-1.75), for the C allele - OR was 1.07 at 95% CI (0.57-2.01). Conclusion: Our studies may indirectly indicate the activation of the skin's protective reaction to physiological scarring and dosed scar formation in different areas of the head and neck.

Técnica Ronaldo Pontes de abdominoplastia em bloco / Ronaldo Pontes block abdominoplasty technique

Introdução: Abdominoplastia é um procedimento não apenas com características estéticas, mas também de reconstrução estrutural da parede abdominal. O objetivo do trabalho é mostrar a experiência dos autores em abdominoplastias, enfocando nos resultados estéticos da cicatriz e a evolução destes pacientes, aplicando as técnicas de ressecção em bloco do Professor Ronaldo Pontes (RP). Métodos: O estudo foi uma série retrospectiva de casos de 124 pacientes, entre março de 2014 a março de 2017, submetidos à abdominoplastia em bloco pela técnica RP. Resultados: Na nossa casuística, demonstrou-se uma mínima incidência de complicações encontradas com a técnica em Bloco RP, em comparação às encontradas na literatura, e, também, demonstrou um número pífio de casos de alterações na cicatrização. Conclusão: A técnica descrita e suas variantes atendem a necessidade de diversos tipos de casos e garantem cirurgias seguras e eficazes, com resultados muito satisfatórios, sendo uma técnica reprodutível.

Introduction: Abdominoplasty involves not only aesthetic characteristics but abdominal wall structural reconstruction. This study aimed to illustrate the authors' experience with abdominoplasty, focusing on the scar's aesthetic results and the evolution of application of the block resection technique of Professor Ronaldo Pontes (RP). Methods: The study included a series of retrospective cases of 124 patients treated between March 2014 and March 2017 who underwent RP block abdominoplasty. Results: In our studies, a minimal incidence of complications and a small number of healing alterations were noted with the RP block technique compared to those found in the literature. Conclusion: A técnica descrita e suas variantes atendem a necessidade de diversos tipos de casos e garantem cirurgias seguras e eficazes, com resultados muito satisfatórios, sendo uma técnica reprodutível.

Seguridad, eficacia y tolerabilidad de un novedoso apósito de gel de silicona para uso posoperatorio en cirugía dermatológica / Safety, efficacy and tolerability of a novel silicone gel dressing for postoperative use in dermatological surgery

Durante muchos años, el gel de silicona ha tenido un rol primario en el tratamiento y la prevención de cicatrices anómalas en forma de cicatrices hipertróficas y queloides luego de la epitelización. Los autores publican los hallazgos preliminares sobre el uso de un novedoso apósito de gel de silicona grado médico que forma una película y que fue aprobado para ser usado en heridas abiertas y en lesiones de la piel como único tratamiento y en combinación con otros tratamientos previos a la reepitelización. Un estudio observacional de 105 pacientes analizó la efectividad del gel de silicona en la estimulación de la epitelización acelerada, la reducción de la respuesta inflamatoria y la prevención de la formación de cicatrices. El estudio se realizó en una variedad de intervenciones quirúrgicas dermatológicas. Las observaciones de los autores confirmaron el rol de la silicona en la aceleración de la cicatrización de heridas, la prevención de la formación de cicatrices y la utilidad de este nuevo apósito de silicona que forma una película cuando se lo combina con otras modalidades de tratamiento. (SKINmed. 2012; 10:S1- S7).

For many years, silicone gel has played a primary role in the treatment of prevention of abnormal scars in the form of after epithelialization. The authors publish the pre-elimination findings use of a novel medical grade silicone gel dressing that form a film that was approved for use in open wounds and in skin as the only treatment and in combination with other treatments prior to re-epithelialization. An observational study of 105 patients analyzed the effectiveness of silicone gel in the stimulation of accelerated epithelialization, reducing the inflammatory response and preventing the formation of scars. The study was conducted on a variety of dermatological surgeries. The authors' observations confirmed the role of silicone in acceleration of wound healing, prevention of the formation of the usefulness of this new silicone dressing that forms a film it is combined with other forms of treatment.