Titanium implants are widely used in treating calvarial defects, and the dura mater exerts regenerative effects on cranial bone regeneration. Three-dimensional (3D) porous titanium scaffolds is advantageous for bone defect repair. This study aims to evaluate the effect of dura on the integration of porous titanium implant and cranial bone. Forty-five adult male New Zealand white rabbits were used to generate cranial defect models; they were randomly divided into 3 groups: calvarial defect with intact dura mater (group I), calvarial defect with partially removed dura mater (group II), and calvarial defect with isolated and intact dura mater (group III). All defects were repaired with porous titanium scaffolds. Micro computed tomography (Micro-CT), three-dimensional (3D) reconstruction, non-decalcified histologic section, and biomechanical examination were used to analyze new bone formation, histological characteristics at 4 and 12 weeks postoperatively. The results showed no implant looseness or infection in any of the groups. Micro-CT revealed a higher bone volume/total volume (BV/TV) and trabecular number (Tb. N) in group I than the other groups at weeks 4 and 12 after implantation. Relative to Groups II and III, the trabecular thickness (Bh.Th) was significantly larger in group I at 12 weeks postoperatively (p < 0.05), while the trabecular separation (Tb. Sp) was smaller in group I at weeks 4 and 12 (p < 0.05 or p < 0.01). Histological analysis showed more newly formed bone and calcification deposition in group I than in the other groups (p < 0.05). Trabecular bone formation was observed under the silicone membrane. The push out force in group I was significantly higher than that in the other groups (p < 0.05). The intact dura mater substantially improved the osteogenesis and osteointegration properties of porous titanium scaffolds. This study provides meaningful implications for improving titanium scaffold osseointegration.

Background Poor blood supply can easily lead to expander extrusion and necrosis at the distal expanded flap. Botulinum toxin A (BTX-A) has been previously found to improve pedicled flap blood flow perfusion, but its effects on the blood supply of expanded skin remain unclear. Therefore, this study aimed to evaluate the effects of BTX-A on blood flow perfusion during and after expansion. Methods Eighteen Sprague-Dawley rats were randomly divided into a BTX-A group and a control group. BTX-A or normal saline was injected intradermally into the marked skin on the back immediately. Then expanders were implanted in the rats. One week later, inflation of the expander with normal saline was started and performed twice a week to reach an intracapsular pressure of 8 kPa. The skin blood flow was measured before each injection. After 4 weeks of expansion, the sample was harvested for histological staining to measure the diameter and density of blood vessels; meanwhile, a 2 cmx 8 cm expanded random flap was elevated and sutured in situ. Blood flow perfusion and flap survival were observed. Results Compared with the control group, the BTX-A group had more blood flow, a larger blood vessel diameter, and higher blood vessel density in the expanded skin. Additionally, the flap of the BTX-A group had good blood flow perfusion and a high proportion of flap survival area within 7 days after expanded flap transfer. Data were analyzed using an independent t-test. Conclusion Pre-surgical BTX-A treatment may increase angiogenesis and vasodilatation, with subsequent blood perfusion elevation during and after expansion, and obtain a greater proportion of survival area of the transferred expanded flap.

To characterise the distribution, classification, and quantity of foamy macrophages (FMs) in tuberculous wound tissue and the relationship between FM and delayed healing of tuberculous wounds. Morphological studies were performed to explore the distribution of FM and Mycobacterium tuberculosis (Mtb) in tuberculous wounds, with acute and chronic wounds included for comparison. Phorbol-12-myristate-13-acetate stimulation-differentiated THP-1 cells were treated with Mtb to induce their differentiation into FM with oxidised low-density lipoprotein treatment serving as a control. Relative cytokine levels were determined by quantitative PCR and Western blotting. Varied co-culture combinations of Mtb, THP-1, FM, and fibroblasts were performed, and proliferation, migration, ability to contract collagen gel, and protein levels of the chemokines in the supernatants of the fibroblasts were assessed. The differentially expressed genes in human skin fibroblasts (HSFs) after co-culture with or without FM were identified using microarray. Many FM were found in the tissues of tuberculous wounds. The FM that did not engulf Mtb (NM-FM) were mainly distributed in tissues surrounding tuberculous wounds, whereas the FM that engulfed Mtb (M-FM) were dominantly located within granulomatous tissues. Co-culture experiments showed that, with the Mtb co-culture, the portions of NM-FM in the total FM grew over time. The migration, proliferation, chemokine secretion, and the ability of fibroblasts to contract collagen gel were inhibited when co-cultured with Mtb, FM, or a combination of the two. Further investigation showed that the TLRs/NF-κB signalling pathway is involved in fibroblast function under the stimulation of FM. TLRs and NF-κB agonists could reverse the phenotypic changes in HSFs after co-culture with FM. The tuberculous wound microenvironment composed of Mtb and FM may affect wound healing by inhibiting the functions of fibroblasts. FM potentially inhibit fibroblasts' function by inhibiting the TLRs/NF-κB signalling pathway in tuberculous wounds.

Keloid is a skin fibroproliferative disease currently having no uniformly successful treatment. The lesion is composed of actively proliferating and collagen-overproducing fibroblasts. LARP6 is an RNA-binding protein able to regulate collagen synthesis in fibroblasts and to promote proliferation and invasion of tumor cells. To explore LARP6's likely functions in keloid pathogenesis, we performed immunohistochemistry staining on human keloid tissues and discovered markedly upregulated LARP6 expression in lesion fibroblasts compared with that of normal skin and hypertrophic scar tissues. In addition, the keloid tissue‒derived fibroblasts showed constitutive upregulation of LARP6 expression as well as significantly upregulated mRNA and protein expressions of type I collagen and enhanced cell proliferation and invasive behavior in cell culture system. Intriguingly, LARP6 knockdown by targeting with small interfering RNAs significantly inhibited type I collagen expression, proliferation, and invasion capability of keloid tissue‒derived fibroblasts relative to that of normal skin‒ and hypertrophic scar‒derived fibroblasts and control keloid tissue‒derived fibroblasts that were transfected with a scrambled small interfering RNA. In conclusion, the abnormally upregulated expression of LARP6 in fibroblasts may play an important role in the growth and invasive behavior of keloid lesions.

Background Burn patients are prone to infection as well as immunosuppression, which is a significant cause of death. Currently, there is a lack of prognostic biomarkers for immunosuppression in burn patients. This study was conducted to identify immune-related genes that are prognosis biomarkers in post-burn immunosuppression and potential targets for immunotherapy. Methods We downloaded the gene expression profiles and clinical data of 213 burn patients and 79 healthy samples from the Gene Expression Omnibus (GEO) database. Immune infiltration analysis was used to identify the proportion of circulating immune cells. Functional enrichment analyses were carried out to identify immune-related genes that were used to build miRNA-mRNA networks to screen key genes. Next, we carried out correlation analysis between immune cells and key genes that were then used to construct logistic regression models in GSE77791 and were validated in GSE19743. Finally, we determined the expression of key genes in burn patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results A total of 745 differently expressed genes were screened out: 299 were up-regulated and 446 were down-regulated. The number of Th-cells (CD4+) decreased while neutrophils increased in burn patients. The enrichment analysis showed that down-regulated genes were enriched in the T-cell activation pathway, while up-regulated genes were enriched in neutrophil activation response in burn patients. We screened out key genes (NFATC2, RORA, and CAMK4) that could be regulated by miRNA. The expression of key genes was related to the proportion of Th-cells (CD4+) and survival, and was an excellent predictor of prognosis in burns with an area under the curve (AUC) value of 0.945. Finally, we determined that NFATC2, RORA, and CAMK4 were down-regulated in burn patients. Conclusion We found that NFATC2, RORA, and CAMK4 were likely prognostic biomarkers in post-burn immunosuppression and potential immunotherapeutic targets to convert Th-cell dysfunction.

Objective:To investigate the application of local rotation flaps for reconstruction of divided nevi of the penises in young male patients.Methods:A group of 8 patients of divided nevi of the penises who underwent wound reconstruction with local rotation flaps after surgical lesion removal was enrolled in a retrospective clinical study. Postoperative complication, sexual function and psychological traits were evaluated during the follow-up.Results:All patients, with ages ranged from 16 to 32 years (mean 23.25 years), were followed up for 6 to 48 months (mean 19.86 months). The patient's average length of hospital stay was 7.85 day (7 to 15 days). The average dimension of the lesions was (2.31±0.44) × (1.46±0.48) cm2 on the glans and (1.38±0.40) × (1.01±0.46) cm2 on the inner prepuce plate. All patients had no postoperative infection and were satisfied with the postoperative outcome upon discharge. Five cases of benign intradermal nevi and 3 cases of compound nevi without malignant transformation were confirmed by pathological evaluation on the removed samples. The sexual function of all patients was unaffected postoperatively by male sexual function scale (BMSFI and IIEF-5) evaluation. The psychological status of depression, anxiety and stress was all improved after the surgical reconstruction confirmed by the psychological traits scale (DASS) evaluation.Conclusion:Reconstruction with the local rotation flap is a simple, safe and appropriate surgical procedure, achieves satisfactory cosmetic outcome, and maintains intact male sexual function when used for the repair of defect after removal of divided nevi of the penises.

Objective: To evaluate the reliability of a rat tuberculous wound model established by injecting Bacillus Calmette-Guérin (BCG). Methods: The experimental research was conducted. According to the random number table, fifteen 6-week-old male Sprague-Dawley rats were divided into normal control group and infection group, with 3 rats in normal control group and 12 rats in infection group. Rats in infection group were injected with Freund's complete adjuvant, 3 weeks later, they were injected subcutaneously with BCG bacterial solution to establish a model of tuberculous wounds in rats; rats in normal control group did not receive any treatment. On the 8th, 15th, 32nd, and 43rd day of infection, the skin condition at the injection sites of the rats in infection group was observed roughly. Skin tissue at the injection sites of 3 rats in infection group at each corresponding time point stated above and skin tissue at the corresponding sites of the rats in normal control group were stained with hematoxylin-eosin to observe the cell arrangement, necrosis and inflammation. On 43rd day of infection, acid-fast staining was performed on the skin tissue at the injection sites of the rats in infection group to observe the distribution of bacteria. Results: On the 8th, 15th, 32nd, and 43rd day of infection, tuberculous wound lesions were gradually developed at the skin tissues at the injection sites of the rats in infection group. The cells of the diseased tissue of the rats in infection group arranged disorderly or concentrically, and the number of granulomas and necrotic cells gradually increased, while the skin tissue cells in the corresponding parts of the rats in normal control group arranged regularly with no inflammatory cell infiltration. On the 43rd day of infection, a large number of rod-shaped bacteria were observed in the skin tissue at the injection sites of the rats in infection group. Conclusions: The rat tuberculous wound model established using BCG is stable and reliable, which can meet the experimental requirements.

Tissue expansion is widely used to obtain new skin tissue for repairing defects in the clinical practice of plastic surgery. One major complication can be dermal thinning during expansion, which usually leads to skin rupture. Collagen synthesis can determine dermal thickness and can be influenced by macrophage polarization during expansion. The aim of the study was to test whether pigment epithelium-derived factor (PEDF) could be a modulator of collagen synthesis in fibroblasts by regulating macrophage polarization during skin expansion. Our results showed that PEDF mRNA expression was increased in expanded human and mouse epidermis. PEDF protein levels were elevated in the subcutaneous exudates of a rat skin expansion model. Increased PEDF mRNA expression was accompanied by dermal thinning during a three-week expansion protocol. Subcutaneous injection of PEDF in vivo further resulted in dermal thinning and cell number increase of M1 macrophage in the expanded skin. PEDF also promoted macrophage polarization in vitro to the M1 subtype under hypoxic conditions. PEDF did not influence collagen gene expression in fibroblasts directly, but attenuated collagen synthesis in a macrophage-mediated manner. Additionally, blockage of PEDF receptors on macrophages with inhibitors rescued collagen synthesis in fibroblasts. Our research demonstrated PEDF elevation in expanded skin leads to dermal thinning through M1 macrophage-mediated collagen synthesis inhibition in fibroblasts. Our results could form a basis for the development of novel strategies to improve skin integrity in expanded skin by using PEDF.

Abstract The expanded pedicled deltopectoral flap (EPDF) has been widely used to repair large facial scars. Although doctors and patients are usually satisfied with the outcomes, the actual functional recovery and cosmetic effects of EPDF are still unknown. It is, therefore, necessary to objectively investigate the effect of transferred EPDF by using a variety of methods. From January 2008 to December 2018, 52 patients who underwent EPDF surgery at Xijing Hospital were enrolled. Sense of touch, static 2-point discrimination, elasticity, and color were measured. Thermesthesia and algesthesia were also tested. Postoperative scars were evaluated using the patient and observer scar assessment scale. Satisfaction of patients, doctors, and laypersons was investigated. The algaesthesis, thalposis, and rhigosis scores were 4.7 ± 0.7, 3.7 ± 0.9, and 4.5 ± 0.8, respectively. The tactile score was 0.3 ± 0.2 mN, and 2-point discrimination was 10.1 ± 4.8 mm. L∗, a∗ hemoglobin, and melanin content of the flaps were significantly different when compared with normal skin (P < 0.05). The satisfaction of doctors, patients, and laypersons was 88.5%, 71.2%, and 67.3%, respectively. The higher satisfaction of patients was mainly associated with the smaller color difference between the flap and the surrounding skin, and lower patient and observer scar assessment scale score. These results confirm that excellent functional recovery and reliable cosmetic effects are observed when facial scars are repaired with EPDF. The methods used in this study can be applied to the evaluation of functional recovery and cosmetic outcomes of transferred flaps, which may provide a more comprehensive understanding of flap assessment.

BACKGROUND The 10,600-nm ablative fractional laser (AFL) is widely used for treating facial atrophic acne scars but with evident side effects. By contrast, the common Er:Glass non-AFL (NAFL) is safer but lacks of comparable outcomes. A novel 1,565 nm Er:Glass NAFL improves thermal energy delivery and could yield better outcomes. OBJECTIVE We aimed to compare the effectiveness and safety between the 1,565-nm NAFL and 10,600-nm AFL in treating mild-to-moderate facial atrophic acne scars. METHODS Nineteen patients with mild-to-moderate bilateral facial atrophic acne scars were enrolled in a randomized split-face trial, which involved 3-session procedures for each laser. The effectiveness and safety were evaluated by doctors and patients who were blinded to the treatment assignment. RESULTS Both lasers improved the acne scar profiles comparably. A marked reduction in erythema, crusting durations, and degree of pain were noted on the sides treated with the 1,565-nm NAFL, relative to those treated with the 10,600-nm AFL. CONCLUSION Both 1,565 nm-NAFL and 10,600-nm AFL can improve mild-to-moderate acne scars. Patients should never expect complete resolution. The 1,565-nm NAFL has less side effects.

Tuberculous wound therapy is a major challenge in clinical practice, due to the protracted disease course, high recurrence rate, and an unclear pathogenesis. We explored the expression patterns of Beclin1 and LC3B in tuberculous wound tissues in human tuberculous chronic wound and normal tissues was assayed by immunohistochemistry. Rat models of tuberculous wounding were induced by the Bacillus Calmette-Guerin (BCG) method. Beclin1 and LC3B protein expression in human tuberculous wound tissues differed from that of normal skin and non-tuberculous chronic wound tissues.In rat tuberculous wound tissues, expression of Beclin1 and LC3B mRNA time-dependently changed post-infection. Abnormal fluctuation of autophagy protein in the development of tuberculosis wound could be one of the causes for the repeated occurrence and protracted disease course of the tuberculous wound.

This study aimed to establish a novel gouty ulcer rat model induced by monosodium urate (MSU) deposition and preliminarily explored how MSU crystals affected wound healing. MSU crystals were subcutaneously injected into the back of rats to simulate tophi formation and ulceration. Ultrasound was used to detect the formation of gouty tophi. MSU crystal deposition and histopathological changes were analysed by haematoxylin–eosin staining. After the skin over the tophi became broken in the model group, a full‐thickness tissue defect of the same area was made on the backs of the phosphate buffered saline (PBS) controls. On Days 3, 7, and 14 after wounding, the infiltration of neutrophils and macrophages and the expression of inflammatory markers, including interleukin‐1β (IL‐1β), tumour necrosis factor‐α (TNF‐α), and Nod‐like receptor protein 3 (NLRP3), were examined by immunohistochemical staining and Western blotting, respectively. After the first subcutaneous injection in rats, local tissues showed redness and swelling, indicating inflammation on approximately Day 14. Tophi‐like manifestations appeared on approximately Day 18. Tophi appeared heterogeneously hyperechoic by ultrasound. Swelling and redness in injured tissue areas increased on approximately Day 22, skin tissue necrosis was seen in a small area on approximately Day 26, and skin necrosis was enlarged and the tophi were ulcerated on approximately Day 32, accompanied by yellowish‐white, chalky secretions. Haematoxylin and eosin staining showed dermal deposition of needle‐like crystals with surrounding granulomatous inflammation. On Days 3, 7, and 14 after wounding, immunohistochemical staining showed the infiltration of neutrophils and macrophages, and the expression of inflammation‐related proteins (IL‐1β, TNF‐α, and NLRP3) were upregulated in gouty ulcers compared with those of PBS controls. The gouty ulcers were not completely healed by Day 14 compared with those in the PBS controls. In this study, a novel gouty ulcer rat model was constructed, which also revealed the existence of persistent chronic inflammation.

Background: Complications associated with ureteral anastomosis in kidney transplantation are highly prevalent, despite the development of various types of stents. The current stent materials and placement methods have several limitations. This study attempts to provide an alternative by investigating ureteral anastomosis with a polyimide stent and a modified placement method in a rat model of kidney transplantation.Methods: Sprague-Dawley rats were randomly divided into Group I: sham operation, Group II: autologous ureteral anastomosis, and Group III: isogenic kidney transplantation with ureteral anastomosis. For the anastomosis, a polyimide stent with a previously placed 11-0 silk was inserted into the ureter. The stent and ureter were fixed with 11-0 silk sutures. The kidney weight and serum creatinine were recorded. The ureteral and renal sections were taken for histological analysis.Results: None of the stents had migrated. Urethral patency was achieved. Further, there were no evident histological changes in the anastomosed ureters. The serum creatinine level in group III was significantly higher than the other two groups, but there was no significant difference in kidney weight among the groups at postoperative week 12. Finally, the histological structure of kidneys in groups II and III only showed minor changes.Conclusions: The current anastomosis method with polyimide stent causes minimal damage to the ureteral walls and minimizes the possibility of stent migration. Therefore, this method of ureteral anastomosis with the polyimide stent should be explored for its potential benefits in more animal kidney transplantation models, thus providing an alternative for the clinical setting.

Foamy macrophages (FM), also known as foam-like macrophages, refer to lipid-laden monocytes or macrophages. FM are a kind of inflammatory cells that are rich in lipid droplets in cytoplasm. In the diseases caused by Mycobacterium tuberculosis (Mtb), such as granuloma and tuberculous wounds, FM can not only inhibit the immune response, but also affect the prognosis and outcomes. The formation mechanisms of FM caused by Mtb infection have some specificity, which may be an important factor for its long-term survival in cells and influences on disease prognosis and outcomes. Therefore, studying the mechanisms of Mtb-mediated formation of FM is conductive to further reveal the pathological evolution of diseases and provide new ideas for further precise treatment. This article reviewed the mechanisms of Mtb-mediated formation of FM in recent years.

BACKGROUND:Hypertrophic scar (HS) is the most common complication after skin injury with unknown etiopathogenesis. There is increasing evidence to suggest that aberrant Notch signaling contributes directly to skin pathogenesis and altered expression of the Notch intracellular domain (NICD) identified in HS. Therefore, the aim of this study was to investigate the effects of Notch signaling pathway in HS pathogenesis.METHODS:Hypertrophic scar and normal skin samples were collected. Notch intracellular domain expression was detected by immunohistochemistry staining and fibroblasts were separated from the samples. We compared fibrotic factors production, cell viability, migration and apoptosis of HS fibroblasts (HFB) versus normal skin fibroblasts (NFB) by real time quantitative polymerase chain reaction, MTS, cell scratch assay and flow cytometry respectively under the impact of inhibition of Notch signaling by NICD-small-interfering RNA (SiRNA).RESULTS:The results showed that NICD was overexpressed in the dermis of HS tissues. Inhibition of Notch signaling by NICD-SiRNA suppressed the production of the fibrotic factors including collagen 1, collagen 3, α-SMA, and TGF-β1 by HFB and NFB. Cell viability and migration were reduced in NICD-SiRNA-treated NFB and HFB, whereas cell apoptosis was enhanced by NICD-SiRNA.CONCLUSIONS:Conclusively, the study demonstrates a potential role for Notch signaling in HS progression, and targeting this pathway may provide a novel strategy for treatment of HS.

Improving periorbital aging is, currently, of great concern. The previous literature has reported some surgical methods for periorbital aging. The purpose of this study was to compare subbrow blepharoplasty (SBB) with subbrow blepharoplasty combined with periorbital muscle manipulation (SBB-pm) with regard to improving periorbital aging. A prospective, randomized, controlled study was designed to evaluate and compare the effects of two different surgical techniques on upper lid relaxation, brow shape and periorbital wrinkles. Patients were divided into two groups. Group 1 underwent resection of excess skin; group 2 underwent a modified technique that involved resection of an elliptical island of skin, separation of the corrugator supercilii muscle and dissection of the orbicularis oculi muscle, followed by suturing it to the orbital periosteum and cross-fixation with itself. The upper eyelid and eyebrow height, periorbital wrinkle score and patient satisfaction were measured preoperatively and postoperatively. This study included 70 patients (140 eyes). At 1 month, 3 months, 6 months and 12 months after surgery, group 2 was superior to group 1 with regard to the improvement in upper eyelid relaxation at the medial limbus, middle pupil and lateral canthus. The eyebrow assumed a low and flat appearance in group 1. The eyebrow showed a low and flat appearance and then returned to the preoperative level in group 2. When comparing the two surgical techniques, the authors found statistically significant differences in regard to changes in crow’s feet and glabellar frown lines. Two patients in group 2 experienced forehead numbness after surgery, which resolved by the 6-month follow-up. Patients in group 2 were significantly more satisfied with their surgery than patients in group 1. SBB-pm is more effective than SBB for improving upper eyelid relaxation and preventing secondary brow ptosis after surgery as well as for alleviating periorbital wrinkles, although it is accompanied by transient forehead numbness. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Skin expansion is widely used in reconstructive surgery to obtain supplemental and optimal skin. Enhancing the regenerative capacity of expanded skin is therefore of great interest. Hair follicle bulge-derived stem cells (HFBSCs) located in hair follicle bulges are closely associated with skin; HFBSC transplantation could promote cutaneous wound repair. However, the effects of transplanted HFBSCs on skin regeneration during expansion remain unclear. The aim of the study was to reveal the potential effects of transplanted HFBSCs in the expanded skin and explore its mechanism. Our results showed higher skin area, tissue weight, epidermal thickness, dermal thickness, proliferating cell count, collagen content, microcirculatory blood flow, blood vessels, and lower retraction ratios were observed in HFBSC-injected rats compared to uninjected controls. Moreover, the transplanted HFBSCs directly contributed to tissue regeneration by differentiating into vascular endothelial cells, epidermal cells, and the outer root sheath cells of hair follicle. Higher expression of EGF, VEGF, bFGF, and TGF-β were observed in HFBSC-injected rats. Our research demonstrated the transplanted HFBSCs could promote skin regeneration by differentiating into various types of skin related cells and by up-regulating the expression of growth factors. Our results could form a basis for the development of novel strategies to enhance regeneration in expanded skin by using HFBSCs.