An Innovative Approach to Classifying and Treating Axillary Scar Contracture.

BACKGROUND: Axillary cicatricial contracture is a debilitating condition that can greatly impair shoulder joint function. Therefore, timely correction of this condition is imperative. In light of Ogawa's prior classification of axillary cicatricial contracture deformities, we have proposed a novel classification system and reconstruction principles based on a decade of treatment experience. Our proposed system offers a more comprehensive approach to correcting axillary cicatricial contracture deformities and aims to improve patient outcomes. METHODS: Our study included 196 patients with a total of 223 axillary cicatricial contracture deformities. The range of shoulder abduction varied between 10 and 120 degrees. Our treatment approach included various methods such as the lateral thoracic flap, transverse scapular artery flap, cervical superficial artery flap, medial upper arm flap, latissimus dorsi flap, Z-shape modification, and the use of local flaps combined with skin grafting. After 2 weeks, the sutures were removed, and patients were instructed to start functional exercises. To categorize the deformities, we divided them into 2 types: axillary-adjacent region cicatricial contracture (type I) and extended area contracture (type II). RESULTS: For each subtype, a specific treatment method was chosen based on a designed algorithm decision tree. Out of the total cases, 133 patients underwent treatment with various types of local flaps, including Z-plasty, whereas 63 patients received treatment involving skin grafting and different types of local flaps. At the time of discharge, the abduction angle of the shoulder joint ranged from 80 to 120 degrees. Among the 131 patients who were followed up, 108 of them adhered to a regimen of horizontal bar exercises. After a 1-year follow-up period, the abduction angle of the shoulder joint had significantly improved to a range of 110-180 degrees. CONCLUSIONS: We have proposed a novel classification method for the correction of axillary cicatricial contracture deformity. This approach involves utilizing distinct correction strategies, in conjunction with postoperative functional exercise, to ensure the effectiveness of axillary reconstruction.

Discovery and Optimization of Novel Biphenyl Derivatives Bearing Cyclopropyl Linkage as Potent Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors.

A series of novel compounds bearing a cyclopropyl linkage were designed, synthesized, and evaluated as programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. An optimized compound (1S,2S)-A25 showed potent inhibitory activity against the PD-1/PD-L1 interaction (IC50 = 0.029 µM) with a selected binding affinity with PD-L1 (KD = 1.554 × 10-1 µM). Additionally, under the co-culture with H460/Jurkat cells, (1S,2S)-A25 can reduce the survival of H460 cells in a concentration-dependent way. A liver microsomal assay revealed that (1S,2S)-A25 had favorable metabolic stability. Furthermore, (1S,2S)-A25 displayed favorable pharmacokinetic properties (oral bioavailability of 21.58%) and potent antitumor potency in a LLC1 lung carcinoma model without observable side effects. Data from the flow cytometry and enzyme-linked immunosorbent assays demonstrated that (1S,2S)-A25 suppressed the tumor growth by activating the immune microenvironment. Our study suggests that (1S,2S)-A25 is a promising lead compound for the further development of PD-1/PD-L1 inhibitors.

Preparation and evaluation of chitosan-polyvinyl alcohol/polyhexamethylene guanidine hydrochloride antibacterial dressing to accelerate wound healing for infectious skin repair.

BACKGROUND: Wound infections, especially multidrug-resistant (MDR) bacterial infections, are a major challenge in clinical medicine. METHODS: In this study, a new type of antibacterial sponge was prepared from a solution containing a chitosan-polyvinyl alcohol (CTS-PVA) emulsion with added polyhexamethylene guanidine hydrochloride (PHMG) in a homogeneous medium using lyophilization technology. The antibacterial ability of and CTS-PVA/PHMG sponge against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Acinetobacter baumannii in vitro. The structure and physical properties were characterized. The sponge dressing was tested in a Pseudomonas aeruginosa-infected full-thickness mouse skin wound defect model. The effects were evaluated by wound area measurement and histological analysis. RESULTS: The CTS-PVA/PHMG sponge showed broad-spectrum antibacterial ability, including for MDR bacterial stains from clinical sources, while maintaining excellent physicochemical properties, including a high swelling degree and good moisture retention capability. Scanning electron microscopy images displayed the surface morphology of the CTS-PVA/PHMG sponge dressing. The detection of the wound healing rate and histological analysis supported that the new dressing can alleviate the inflammation and accelerate the healing speed of infected wounds and in vivo. CONCLUSIONS: CTS-PVA/PHMG sponge shows broad-spectrum antibacterial activity, which can provide a new pathway for clinical prevention and treatment of superbug-infected wounds.

Down-Regulation of miR-301a-3p Reduces Burn-Induced Vascular Endothelial Apoptosis by potentiating hMSC-Secreted IGF-1 and PI3K/Akt/FOXO3a Pathway.

Vascular endothelium dysfunction plays a pivotal role in the initiation and progression of multiple organ dysfunction. The mesenchymal stem cell (MSC) maintains vascular endothelial barrier survival via secreting bioactive factors. However, the mechanism of human umbilical cord MSC (hMSC) in protecting endothelial survival remains unclear. Here, we found IGF-1 secreted by hMSC suppressed severe burn-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and alleviated the dysfunction of vascular endothelial barrier and multiple organs in severely burned rats. Severe burn repressed miR-301a-3p expression, which directly regulated IGF-1 synthesis and secretion in hMSC. Down-regulation of miR-301a-3p decreased HUVECs apoptosis, stabilized endothelial barrier permeability, and subsequently protected against multiple organ dysfunction in vivo. Additionally, miR-301a-3p negatively regulated PI3K/Akt/FOXO3 signaling through IGF-1. Taken together, our study highlights the protective function of IGF-1 against the dysfunction of multiple organs negatively regulated by miR-301a-3p, which may provide the theoretical foundation for further clinical application of hMSC.

Analysis of Factors Affecting Chronic Ulcers of Scalp Transforming Into Marjolin's Ulcer: A Single Center Experience.

The Marjolin's ulcer (MU) is a rare malignant lesion, which is characterized by primary, chronic wound initially and formation of cancer after a certain incubation period eventually. Though few reports or a small case series about MU on the scalp have been published, special risk factors are still unknown about the formation of malignancy on the scalp with chronic ulcer. The aim of the article is to explore the risk factors. Seventy-four patients with the chronic ulcer were included in the study. In between, the chronic ulcer transformed into the MU on the scalp (tumor group) in 42 cases, while the chronic ulcer did not transform into the MU on the scalp (tumor-free group) in 32 cases as controlled group. We made a comparative study between the above two groups so as to find which risk factors were critical for cancer development. In tumor group, lymph node dissection was implemented if the lymph node metastasis was found. Artificial dura was used in eight cases when the dura was removed. Seven cases died. Two patients are currently undergoing follow-up. Other cases were without tumor detection from 1 to 7 years. When the comparative study between the above two groups, there is statistical significance about the influential factor: scar adherence to the skull (F = 5.602 P = .018). Scar adherence to the skull may be the most critical risk factor for cancer development for the scalp with chronic ulcer.

Statistical analysis of factors affecting re-operative times in paediatric patients with scar deformity after deep second-degree burn injury.

Deep second-degree burn injuries pose a challenge for treating scar deformity in developing paediatric patients. Some patients underwent several re-operations during their development. There was no literature reporting which factors affect re-operative times. In this article, we intend to analyse possible influential factors that are responsible for re-operative times in paediatric patients with scar deformity after deep second-degree burn injuries. From 2010 to 2016, 177 paediatric cases with a history of deep second-degree burn injury who underwent re-operation once, twice, and equal to or more than thrice were recruited to this study, with age ranging from 0 to 18 years. The following factors were analysed: age, gender, size of scar, method for reconstruction, location, postoperative anti-scar treatment, preschool group, school group, combined deformity, and combined method for reconstruction. One-way ANOVA and multi-way ANOVA analysis were used as statistical tools to analyse the above factors and re-operative times. There were 83 male cases and 94 female cases, with an average age of 7.47 years. Statistical significance was achieved for the size of scar (P = 0.000), operation method (P = 0.001), and combined deformity (P = 0.026) under 1-way ANOVA in different re-operative times. The operation methods for the head and neck area (P < 0.05) and the lower extremities (P < 0.05) are critical factors for multi-factor variance analysis in different re-operative times. Multivariate logistic regression analysis also demonstrated that the size of scar was an independent risk factor for the number of operations. Combined operative method was a protective risk factor for the number of operations. There was no statistical significance obtained for other factors. Size of scar, operation method, and combined operation method are the risk factors for re-operative times, while operation methods for the head and neck area and lower extremities are the critical factors for re-operative times. We can use the combined method to resolve scar-related problems in order to reduce re-operative times.

[Effects of PRX-2 gene on the phenotype changes of epidermal stem cells differentiating into sweat gland cells].

Objective: To investigate the effects of PRX-2 gene on phenotype changes in epidermal stem cells differentiating into sweat gland cells. Methods: Epidermal stem cells and sweat gland cells separated and cultured from healthy foreskin and adult full-thick skin respectively, were identified by immunofluorescence staining. Lentiviral vector-mediated overexpression and knockdown of PRX-2 gene in epidermal stem cells were performed respectively,with empty vector-mediated epidermal stem cells as a control group. Overexpression blank control and know down group's PRX-2 expressions in gene and protein levels were detected using RT-PCR and Western blot technology. The ESCs of each group were co-cultured with sweat gland cells through transwell plate, and the expressions of CEA and ß1 integrin in epidermal stem cells were determined by flow cytometry before and after co-culturing. Results: Epidermal stem cells and sweat gland cells were in line with their respective specific antigens .Before co-cultured, epidermal stem cells highly expressed ß1 integrin (98.69 ± 0.67)％,hardly expressed CEA (6.20 ± 3.15)％.After co-cultured,ß1 integrin expression levels were showed as knockdown group (19.30 ± 0.53) ％ ＜blank control group (65.77 ± 2.32)％ ＜ overexpress group (92.63 ± 10.97)％,and CEA expression levels as knockdown (95.43 ±2.36)％ ＞ blank control group (51.20 ±0.79)％ ＞ overexpress group (45.91 ±0.93)％.There had significant differences between those of each two groups. Conclusions: PRX-2 gene can inhibit the phenotypic change of Epidermal Stem Cells differentiating into Sweat Gland Cells and improve the ability to maintain their own specific antigens.

[PHENOTYPIC CHANGES OF EPIDERMAL STEM CELLS DIFFERENTIATING INTO SWEAT GLANDS CELLS IN VITRO AND ITS MECHANISM].

OBJECTIVE: To explore the phenotypic changes of epidermal stem cells (ESCs) differentiating into sweat glands cells (SGCs) in vitro and its mechanisms. METHODS: ESCs and SGCs were isolated and cultured in vitro, which were identified using immunofluorescence staining. ESCs at passage 2 were divided into 4 groups: ESCs and SGCs co-cultured by Transwell plates in group A, ESCs cultured by simply adding sweat supernatant in group B, ESCs and SGCs co-cultured on Transwell plate adding epidermal growth factor (EGF) (60 ng/mL) in group C, and ESCs and SGCs co-cultured on transwell plate adding PD98059 (10 mmol/L) in group D. The inverted microscope was used for observing the morphology of ESCs, flow cytometry for detecting ESCs positive phenotype, and Western blot for exploring mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway. RESULTS: The morphology observation and immunofluorescence staining suggested that cultured cells were ESCs and SGCs. The inverted phase contrast microscope observation showed that cells had similar morphological changes, with flat polygonal shape at 9 days in groups A, C, and D; cells had slow morphological change in group B, and had similar change to that of other groups at 12 days. Significant decreasing of beta1-integrin expression and increasing of carcino-embryonic antigen (CEA) expression of ESCs were observed in group A when compared with group B, which was inhibited by EGF (group C) and enhanced by PD98059 (group D), and there were significant differences among groups A, C, and D (P<0.05). High level of ERK expression was displayed in 4 groups, but it was significantly lower in group B than the other 3 groups (P<0.05). The expression of phosphorylation ERK was the highest in group A and was the lowest in group C, showing significant difference among 4 groups (P<0.05). CONCLUSION: ESCs can be induced to differentiate into SGCs with the phenotypic changes under the condition of co-cultured by Transwell plates. The MAPK/ERK pathway plays a key role in the diffrentation of ESCs into GCCs