Objective: To explore the effects of pulsed dye laser (PDL) and ultra-pulsed fractional carbon dioxide laser (UFCL) combined with multipoint microinjection of triamcinolone acetonide in the treatment of red hypertrophic scar at early stage in burn children. Methods: A retrospective cohort before-after control study in the same patients was conducted. From February 2019 to December 2020, a total of 67 burn children who met the inclusion criteria (32 males and 35 females, aged 1 to 12 years) with red hyperplastic scar at early stage, were treated in Hunan Provincial People's Hospital (1^st Affiliated Hospital of Hunan Normal University). All the children were treated with composite laser technique (PDL and UFCL) combined with triamcinolone acetonide (hereinafter referred to as combined treatment). After 2 months, they received the second combined treatment. Before the first combined treatment and 6 months after the last combined treatment, the scar of children was evaluated with the patient and observer scar assessment scale (POSAS) by physicians and family members. Six months after the last combined treatment, the satisfaction of the patients' family members with the efficacy was recorded and the overall satisfaction rate was calculated. Adverse reactions were recorded throughout the treatment process. Data were statistically analyzed with paired sample t test. Results: Six months after the last combined treatment, the POSAS scores of children on the thickness, blood vessels distribution, color, surface roughness, texture, scope, and overall evaluation of scar evaluated by the physicians, and the POSAS scores of children on the color, degree of pain, degree of itching, hardness, thickness, shape and size, and overall evaluation of scar evaluated by the family members were significantly lower than those before the first combined treatment (with t values of 17.32, 16.73, 15.00, 14.91, 19.62, 28.74, 29.83, 17.43, 20.52, 29.01, 28.82, 24.91, 20.30, and 42.13, respectively, P<0.01). Six months after the last combined treatment, 62 (93%), 3 (4%), and 2 (3%) children's family members were very satisfied, satisfied, and relatively satisfied with the treatment effect, respectively, and the overall satisfaction rate was 97% (65/67). Six months after the last combined treatment, no scar thickening or infection occurred in all the wounds of children. Conclusions: Composite laser technique combined with multipoint microinjection of triamcinolone acetonide in the treatment of red hypertrophic scar at early stage in burn children can improve the appearance and texture of scar, reduce scar pain and pruritus, with high satisfaction of children's family members to the treatment effect and less adverse reactions.
Burns/therapy* ; Child ; Cicatrix, Hypertrophic/pathology* ; Female ; Humans ; Lasers, Gas ; Male ; Microinjections ; Pain ; Pruritus ; Retrospective Studies ; Treatment Outcome ; Triamcinolone Acetonide/therapeutic use*

Hypertrophic scar is a pathological repair result of excessive accumulation of extracellular matrix after skin damage, which affects the appearance and function of patients with varying degrees. The degree of scar formation is directly related to the strength of inflammatory reaction during wound healing, and excessive or prolonged inflammatory response increases the incidence of hypertrophic scars. Interleukin-6 (IL-6) is a pleiotropic cytokine that is involved in regulating the fibrotic network composed of fibroblasts, macrophages, keratinocytes, and vascular endothelial cells, and is closely related to the formation of hypertrophic scars. This article reviews the role of IL-6 and its signaling pathway in hypertrophic scar formation.
Cicatrix, Hypertrophic/pathology* ; Endothelial Cells/metabolism* ; Fibroblasts/metabolism* ; Humans ; Interleukin-6 ; Skin/pathology* ; Wound Healing/physiology*

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.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Aspirin/therapeutic use* ; Cicatrix, Hypertrophic/pathology* ; Collagen ; Rabbits ; Signal Transduction ; Triamcinolone Acetonide/therapeutic use* ; beta Catenin/metabolism*

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.
Analgesia ; Analgesics ; Child ; Cicatrix, Hypertrophic/pathology* ; Dizziness/drug therapy* ; Female ; Headache/drug therapy* ; Humans ; Ibuprofen/therapeutic use* ; Lasers, Gas/therapeutic use* ; Lidocaine ; Male ; Nausea/drug therapy* ; Pain/drug therapy* ; Prospective Studies ; Treatment Outcome ; Vomiting/drug therapy*

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.
Animals ; Cicatrix, Hypertrophic/pathology* ; Endothelial Cells ; Matrix Metalloproteinase 2 ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transforming Growth Factor beta1 ; Vascular Endothelial Growth Factor A

PURPOSE: This study investigated the morphological characteristics of hypertrophic scars of various ages. METHODS: This was a retrospective study. Tissue samples from 170 normal skin (control) and 126 scar tissue after undergoing conservative treatment (CT) (n=62) or split thickness skin graft (STSG) (n=64) were obtained. Time from injury (CT) or surgery (STSG) was grouped into periods as follows: first 6 months (period 1), 7~12 months (period 2), 13~24 months (period 3), 25~120 months (period 4), >120 months (period 5). Epidermal thickness (ET), dermal thickness (DT), and dermal collagen fiber thickness and length (CFT, CFL) were measured using an image analyzer. RESULTS: Scar tissue ET was significantly thicker compared to normal skin (P<0.05) and was greatest at period 1. Scar tissue DT was significantly thicker compared to normal skin (P<0.05), which increased until period 3 but then decreased afterwards. Scar tissue CFT was significantly thinner compared to normal skin (P<0.05) except for period 5. Scar tissue CFL was significantly longer compared to normal skin (P<0.05). Significant differences were observed especially in younger scar ET, DT, CFT, and CFL. CONCLUSION: These findings may assist to increase the understanding of the pathohistological changes in burn scar tissues over time and provide guidance in receiving burn treatment.
Burns ; Cicatrix* ; Cicatrix, Hypertrophic* ; Collagen ; Pathology ; Retrospective Studies ; Skin ; Transplants

OBJECTIVETo investigate whether administrating Abnormal Savda Munziq (ASMq), a traditional Uighur herbal preparation used for the prevention or treatment of diseases, affects hypertrophic scar (HTS) formation by using an established rabbit ear model.

METHODSThe HTS rabbit model was created by circular fullthickness skin excisions on both ears of rabbits. Twenty rabbits were randomized into four groups, with 5 rabbits and 60 wounds in each group. Group A was the control group, treated with normal saline daily. Groups B, C, and D were the treatment groups at three different doses of ASMq (400, 800, and 1200 mg/kg body weight, respectively, daily, by gastrogavage). Twenty wounds were randomly chosen from each group on the 40th day after treatment and specimen were examined. Scar elevation index (SEI) was analyzed with histological assessment, and ultrastructure analysis was analyzed with a transmission electron microscopy.

RESULTSGroups B, C, and D demonstrated significant reductions in SEI as compared with the control group at 35.9% (P=0.0212), 48.2% (P=0.0108), and 52.7% (P=0.0103), respectively in a dose-response manner. SEI was lowered in Group D compared with Group B with a significant difference (P=0.015). However, there were no significant differences between Groups B and C, or between Groups C and D. Histological analysis showed that highdose ASMq (1200 mg/kg) could enhance the softening of HTS of rabbit ears and increase the compliance as shown in general. Ultrastructure analysis showed that with increased ASMq dose, the fibroblasts, pro-collagen, collagen, endoplasmic reticulum and ribosomes were reduced gradually.

CONCLUSIONSOrally administered ASMq significantly reduces the severity of HTS in the rabbit ear model. The findings of this study may have clinical implications on the management of human HTS.

Animals ; Cicatrix, Hypertrophic ; drug therapy ; pathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ear ; pathology ; Female ; Plant Extracts ; pharmacology ; therapeutic use ; Rabbits ; Wound Healing ; drug effects

OBJECTIVETo investigate the effect of epidermal stem cells from human hypertrophic scar (HS-ESCs) on the skin wound healing in nude mice.

METHODS40 mice were randomly divided into two groups as experimental group (n = 20) and control group (n = 20). Wounds, 1 cm in diameters, were made on every mouse back. The wounds were treated with HS-ESCs and erythromycin ointment in experimental group, or only with erythromycin ointment in control group. The wound healing was observed during the following 14 days. The expression of collagen-I, collagen-III, epidermal growth factor (EGF), fibroblast growth factor (FGF2) , transforming growth factor (TGFbeta1, and TGFbeta2) were studied.

RESULTSThe wound healing time in the experimental group was (20.8 +/- 0.84) d, which was (25.6 +/- 0.89) d in the control group. HE staining revealed that the extent of vascularization in the experimental group was 11.60 +/- 0.55, while it was 8.04 +/- 0.33 in the control group. Immunochemistry analysis showed the expression of collagen-I, collagen-III, EGF, FGF2, TGFbeta1, and TGFbeta2 in the experimental group were significantly higher, compared with those in control group (P < 0.05).

CONCLUSIONHS-ESCs may promote wound healing through enhancement of the vascularization of the wound tissue and the expression of growth factors.

Animals ; Cicatrix, Hypertrophic ; pathology ; Epidermis ; cytology ; Female ; Humans ; Male ; Mice ; Mice, Nude ; Skin ; injuries ; Stem Cell Transplantation ; Stem Cells ; Wound Healing

OBJECTIVETo explore the effects of pressure therapy on proliferation and apoptosis of cells in hypertrophic scar (HS) of burn patients.

METHODSTwenty patients who were hospitalized from September 2010 to September 2012 and started to wear pressure garment tailored by rehabilitation therapists over 20 hours a day beginning from two weeks after healing of burn wounds with the depth from deep partial-thickness to full-thickness (early stage of formation of HS) were set as pressure treatment group (PT). Another group of patients who were hospitalized in the same period with HS formed 3, 6, 12, 24 months (with 5 patients at each time point) after deep partial-thickness to full-thickness burns without receiving any treatment were set as control group. HS tissue samples from limbs and face were excised at post treatment month (PTM) 3, 6, 12, 24 in group PT (with 5 patients at each time point), and 2 to 3 days after admission in control group. Five patients out of the above-mentioned 40 patients were selected according to the random number table, and normal skin tissue samples from abdomen and thigh were also obtained to serve as normal control. The expressions of proliferating cell nuclear antigen (PCNA) in HS and normal skin tissue were determined with immunohistochemical staining. The apoptosis status was detected with situ end labeling technique. The mRNA expressions of P57(kip2) and Cyclin E were determined with real-time fluorescence quantification PCR. Data were processed with t test, one-way analysis of variance, or LSD test.

RESULTS(1) In normal skin tissue, PCNA-positive cells were observed in the epidermal basal layer and prickle cell layer. In group PT and control group, PCNA-positive cells were observed in the epidermal basal layer, prickle cell layer, lower part of the granular cell layer, and dermis of HS. The percentages of PCNA-positive cells in HS in group PT were respectively (40.4 ± 2.9)%, (28.2 ± 6.2)%, (9.9 ± 0.7)% at PTM 3, 6, 12, which were significantly lower than those of HS formed 3, 6, 12 months after wound healing in control group [(48.3 ± 4.7)%, (36.2 ± 3.2)%, (11.4 ± 0.9)%, with t values respectively 3.186, 2.559, 2.880, P values all below 0.05]. (2) In normal skin tissue, apoptotic cells were observed in the epidermal basal layer. In group PT and control group, apoptotic cells were observed in each layer of epidermis of HS. The apoptotic indexes of HS in group PT were respectively (20.4 ± 1.2)%, (26.1 ± 0.4)%, (26.6 ± 1.0)% at PTM 6, 12, 24, which were significantly higher than those of HS formed 6, 12, 24 months after wound healing in control group [(16.2 ± 1.5)%, (23.1 ± 2.0)%, (24.8 ± 1.1)%, with t values respectively -4.904, -3.366, -2.606, P < 0.05 or P < 0.01]. (3) The mRNA expressions of P57(kip2) of HS in group PT were respectively 3.87 ± 0.20, 8.60 ± 0.78, 10.00 ± 0.57 at PTM 3, 6, 12, which were significantly higher than those of HS formed 3, 6, 12 months after wound healing in control group (3.34 ± 0.15, 6.36 ± 0.29, 9.34 ± 0.12, with t values respectively -4.880, -6.014, -2.375, P < 0.05 or P < 0.01). The mRNA expression of P57(kip2) in normal skin tissue was close to those of HS in group PT at PTM 12, 24 and those of HS formed 12, 24 months after wound healing in control group (with P values all above 0.05). (4) The mRNA expressions of Cyclin E of HS in group PT were respectively 19.30 ± 0.18, 12.77 ± 0.30, 9.21 ± 0.18 at PTM 3, 6, 12, which were significantly higher than those of HS formed 3, 6, 12 months after wound healing in control group (19.79 ± 0.34, 15.41 ± 0.26, 9.47 ± 0.17, with t values respectively 3.186, 2.559, 2.880, P < 0.05 or P < 0.01). The mRNA expression of Cyclin E in normal skin tissue was close to those of HS in group PT at PTM 12, 24 and those of HS formed 12, 24 months after wound healing in control group (with P values all above 0.05).

CONCLUSIONSPressure therapy can accelerate the evolution process of HS through accelerating apoptosis and inhibition of cell proliferation, thereby scar proliferation is inhibited.

Adult ; Apoptosis ; Burns ; complications ; rehabilitation ; Cell Proliferation ; Cicatrix, Hypertrophic ; pathology ; therapy ; Compression Bandages ; Female ; Humans ; Male ; Pressure

OBJECTIVETo evaluate in vitro effect of abnormal savda munziq (ASMq) on the proliferation and apoptosis of human hypertrophic scar fibroblasts (HSFs).

METHODSHSFs were divided into six groups to receive different treatments as group A (blank control group), group B-E (ASMq in different concentration), and group F(5-Fu). Each group contains six specimens. The HSFs were cultured in vitro. After culture for 48 hours, the CCK8 test and flow cytometry methods were used to detect the proliferation, cell cycle and apoptosis.

RESULTSThe proliferation of HSFs in the B, C, D and E groups was inhibited at G2/M period, while it was inhibited at G0/S period in group F (P < 0.05). The inhibition effect of ASMq (0.1-1.0 mg/ml) on the fibroblasts enhanced in a concentration-dependent manner. Flow cytometry analysis with annexin V-FITC and PI staining confirmed the apoptotic. When HSFs were exposed to ASMq at 1.0 mg/ml (group E) for 48 h, the percentage of apoptotic cells increased to (43.7 +/- 2.58)%, which was significantly higher than that of blank control group (2.2 +/- 0.59)%. The induced apoptosis effect was also increased in a concentration-dependent manner.

CONCLUSIONASMq has a inhibitory effect on the proliferation and an enhancement effect on the apoptosis of fibroblast. ASMq could be used as an effective drug for treatment of hypertrophic scar.

Apoptosis ; Cell Cycle ; drug effects ; physiology ; Cell Division ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix, Hypertrophic ; pathology ; Fibroblasts ; cytology ; drug effects ; Flow Cytometry ; Humans ; In Vitro Techniques ; Medicine, East Asian Traditional