Antiphospholipid syndrome presenting as extensive skin ulcers on unilateral lower extremity: a case report.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial and venous thrombosis, habitual fetal miscarriages, often accompanied by mild to moderate thrombocytopenia, and persistent moderate-to-high titer positivity for antiphospholipid antibodies (aPLs). However, patients with antiphospholipid antibodies may also present with several nonthrombotic clinical manifestations, such as thrombocytopenia, cardiac valve disease, nephropathy, skin ulcers, or cognitive dysfunction, which are collectively referred to as nonstandard manifestations of APS. Of these, for APS with predominantly cutaneous ulcers, previous reports have focused on APS with combined cutaneous vasculitis, and its medical treatment, rather than cutaneous ulcers with predominantly fatty inflammatory lesions, and the associated surgical treatment. Here, we admitted a relatively rare case of primary APS with extensive skin ulceration of the right lower extremity, without cutaneous vasculitis, in the presence of extensive and severe inflammatory lipoatrophy, carrying anti-ß2-glycoprotein I and lupus anticoagulant, which is reported as follows, with a view to raising awareness of this disease.

EphB3 receptor suppressor invasion, migration and proliferation in glioma by inhibiting EGFR-PI3K/AKT signaling pathway.

Eph receptors are the largest subfamily of receptor tyrosine kinases, and they have been shown to play a crucial role in glioma. The EphB3 receptor is a member of this family, and its effect on the invasion, migration and proliferation of glioma cells was examined in this study. It was found that the expression of EphB3 was decreased in glioma specimens with increasing tumor grade. Additionally, the U87MG and U251 cell lines showed low levels of EphB3 expression. This finding was consistent with the negative correlation between EphB3 expression in glioma tissues and tumor grade. Depletion of EphB3 gene in U87MG and U251 cell lines resulted in a substantial enhancement of their invasion, migration, and proliferation capacities in vitro. Furthermore, the knockdown of EphB3 led to an upregulation of EGFR, p-PI3K, and p-AKT protein levels. On the other hand, EphB3 overexpression reduced the invasiveness, proliferative capacity and migration rate of U87MG and U251 cells, and downregulated EGFR, p-PI3K and p-AKT. These findings indicate that EphB3 functions as a tumor suppressor in glioma, and its downregulation enhances the malignant potential of glioma cells by activating the EGFR-PI3K/AKT pathway. Thus, EphB3 is a promising diagnostic marker for glioma, and the EphB3-EGFR-PI3K / AKT axis deserves further investigation as a potential therapeutic target.

Eschar Dermabrasion in Deep Dermal Partial-Thickness Burn: A Case Report.

ABSTRACT: Although dermabrasion is widely used to treat various skin diseases and for scar repair, relatively few reports have described its use with burn wounds. As a blunt debridement, eschar dermabrasion has unique advantages. For patients with deep burns, the boundary between active tissue and inactive tissue is unclear. With eschar dermabrasion, necrotic tissue can be removed to the greatest extent with minimal damage. Early use can help patients skip the scab-dissolving period, decrease local and systemic inflammation, reduce postoperative scarring, and significantly reduce the difficulty of early wound care. As a result, the patient's hospitalization costs and pain during treatment are both reduced, and thanks to less scarring, the patient is more likely to engage in social activities and has an improved quality of life.

Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family.

The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

An improved bone transport surgical method for treating chronic ischemic ulcers (thromboangiitis obliterans).

Introduction: The chronic ischemic injury of the upper/lower limbs caused by thromboangiitis obliterans (TAO, Buerger's disease) is difficult to heal, leading to high morbidity and amputation risk, seriously lowering the quality of life of patients. So far, the pathogenesis of this disease is still not clear, and there are still no effective therapeutic approaches. Here, we first use an improved bone transport technique to treat TAO-related foot ulcers and achieve good therapeutic effects. Materials and Methods: In this report, 22 patients met the inclusion criteria, and we provide an improved bone transport technique to repair TAO-related chronic lower limb wounds, which have a minimally surgical incision and a satisfying surgical field. Results: The improved bone transport technique resulted in TAO-related chronic lower extremity wound healing in most patients (18, M:F 16:2) within the first treatment cycle. All wounds healed completely after two treatment cycles. After these cycles, the cold sensation in the patients' feet was significantly relieved, and the rest pain in the lower extremities was significantly relieved (Visual Analog Scale, P < 0.0001). Furthermore, the Laser Doppler flowmeter showed that the blood perfusion and percutaneous oxygen pressure of the affected foot were higher than in preoperation (P < 0.0001). To conclude, bone transport technology is available for the refractory wounds of the extremity, which may promote healing by increasing blood circulation and tissue oxygen supply. Conclusions: In summary, the improved surgical method of the bone transport technique is worth considering in the treatment of thromboangiitis obliterans-related foot ulcers.

A Rule of Thumb for Evaluating Surface Areas of Chronic Wounds.

BACKGROUND: Rapid estimation of the area of chronic wounds is clinically important. A simple method using the thumb was investigated for universal physical measurement, particularly of small and multiple wounds; the thumb surface area (TSA) was then compared with the total body surface area (TBSA). METHODS: A cross-sectional observational study and random sampling were used to obtain the characteristics of 343 participants. Data related to handprint surface area of the thumb and palm were collected using a scanner and laptop and assessed using image software. The TSA as a percentage of TBSA was confirmed based on the traditional rule that regards palmar surface area as 1% of TBSA. Information on factors potentially influencing measurement was gathered with questionnaires to analyze correlations. RESULTS: The left and right TSAs were on average 4.27% and 4.28%, respectively, of the palmar surface area for all participants. Multiple linear regression analysis found that male and older participants had higher TSA:TBSA proportions (sex, P = .0020; age, P < .0001). The TSA:TBSA proportion increased by age for both males (by age group, 0.0418%, 0.0426%, 0.0432%, and 0.0460%, respectively) and females (0.0400%, 0.0409%, 0.0427%, and 0.0430%, respectively). CONCLUSIONS: Thumb size is relatively stable in relation to TBSA, lending itself to a universal method for estimating the size of chronic wounds as a percentage of TBSA. It therefore represents a convenient physical measurement for assessing the area of burns and other wounds.

Co-administration of platelet-rich plasma and small intestinal submucosa is more beneficial than their individual use in promoting acute skin wound healing.

Background: Acute skin wounds may compromise the skin barrier, posing a risk of infection. Small intestinal submucosa (SIS) is widely used to treat acute and chronic wounds. However, the efficacy of SIS to accelerate wound healing still needs to be improved to meet clinical demands. To tackle this problem, platelet-rich plasma (PRP) is used due to its potency to promote proliferation, migration and adhesion of target cells. In this study, we applied PRP and SIS to skin wounds to explore their effects on wound healing by evaluating re-epithelialization, collagen production, angiogenesis and the inflammatory response. Methods: A 1 × 1-cm full-thickness skin defect was established in mice. Sixty mice were divided into four treatment groups: PRP + SIS, PRP, SIS and control. On days 3, 5, 7, 10 and 14 post-surgery, tissue specimens were harvested. Haematoxylin and eosin, Masson's trichrome, immunohistochemical and immunofluorescence double staining were used to visualize epidermal thickness, collagen and vascular regeneration and inflammation. Results: Wound contraction in the PRP and PRP + SIS groups was significantly greater, compared with the other groups, on days 3 and 5 post-surgery. A histological analysis showed higher collagen expression in the PRP and PRP + SIS groups on day 7, which was associated with a thicker epidermal layer on day 14. In addition, immunohistochemical staining showed that CD31-positive blood vessels and vascular endothelial growth factor expression in the PRP + SIS and PRP groups were significantly higher, compared with the control group. Furthermore, immunofluorescence double staining showed that the number of M1 and M2 macrophages in the PRP + SIS and PRP groups was higher, compared with the control and SIS groups alone, on day 3. However, on day 7, the number of M1 macrophages dramatically decreased in the PRP + SIS and PRP groups. The ratio of M2 to M1 macrophages in the PRP + SIS and PRP groups was 3.97 and 2.93 times that of the control group and 4.56 and 3.37 times that of the SIS group, respectively. Conclusion: Co-administration of SIS and PRP has a better effect on promoting angiogenesis, re-epithelialization and collagen regeneration in managing acute wound healing than either agent alone.

Human Salivary Histatin-1 Is More Efficacious in Promoting Acute Skin Wound Healing Than Acellular Dermal Matrix Paste.

A rapid wound healing is beneficial for not only recovering esthetics but also reducing pain, complications and healthcare burdens. For such a purpose, continuous efforts have been taken to develop viable dressing material. Acellular dermal matrix (ADM) paste has been used to repair burn wounds and is shown to promote angiogenesis as well as fibroblast attachment and migration. However, its efficacy still needs to be significantly improved to meet clinical demands for accelerating acute skin wound healing. To approach this problem, we studied the added value of a human salivary peptide - Histatin 1 (Hst1). Hst1 was chosen because of its potency to promote the adhesion, spreading, migration, metabolic activity and cell-cell junction of major skin cells and endothelial cells. In this study, we hypothesized that ADM paste and Hst1 showed a better effect on the healing of surgically created acute skin wounds in mice since ADM paste may act as a slow release system for Hst1. Our results showed that the healing efficacy of 10 µM topically administrated Hst1 was significantly higher compared to the control (no Hst1, no ADM) from day 3 to day 10 post-surgery. In contrast, ADM alone failed in our system at all time points. Also, the combination of ADM paste and Hst1 did not show a better effect on percentage of wound healing. Histological analysis showed that 10 µM Hst1 was associated with maximal thickness of newly formed epidermal layer on day 7 as well as the largest collagen area on day 14. In addition, immunohistochemical staining showed that the number of CD31-positive blood vessels in the group of 10 µM Hst1 was 2.3 times compared to the control. The vascular endothelial growth factor (VEGF) expression in the groups of 10 µM Hst1 group and ADM + 10 µM Hst1 group was significantly higher compared with the control group. Furthermore, 10 µM Hst1 group was associated with significantly lower levels of CD68-positive macrophage number, interleukin-1ß (IL-1ß) expression and C-reactive protein (CRP) expression than those of the other groups (control, ADM alone and ADM + 10 µM Hst1). In contrast, ADM was only associated with significantly lower CD68-positive macrophage number and IL-1ß expression in comparison with the control. The co-administration of Hst1 and ADM paste did not yield more beneficial effects than Hst1 alone. In conclusion, the topically administrated of 10 µM Hst1 could be a promising alternative dressing in managing acute wound healing.

Changes in Foot Skin Microbiome of Patients with Diabetes Mellitus Using High-Throughput 16S rRNA Gene Sequencing: A Case Control Study from a Single Center.

BACKGROUND Worldwide, the treatment of complications associated with type 2 diabetes mellitus, including diabetic foot ulcer (DFU), results in an economic burden for patients and healthcare systems. This study aimed to use high-throughput 16S rRNA gene sequencing to investigate the changes in foot skin microbiome of patients with diabetes mellitus from a single center in China. MATERIAL AND METHODS Fifty-two participants were divided into 4 study groups: healthy controls (n=13); patients with short-term diabetes (<2 years; n=13); patients with intermediate-term diabetes (5-8 years; n=13); and patients with long-term diabetes (>10 years; n=13). Swabs were analyzed from the intact skin of the foot arch using high-throughput 16S ribosomal RNA sequencing. RESULTS Microbiome phylogenic diversity varied significantly between the study groups (whole tree, P<0.01; Chao1, P<0.01), but were similar within the same group. The findings were supported by non-parametric multidimensional scaling (stress=0.12) and principal component analysis (principal component 1, 8.38%; principal component 2, 5.28%). In patients with diabetes mellitus, the dominant skin microbial phyla were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. CONCLUSIONS High-throughput 16S rRNA gene sequencing showed dynamic changes in the skin microbiome from the foot during the progression of diabetes mellitus. These findings support the importance of understanding the role of the skin microbiota in the pathogenesis of DFU.

Human-microorganism mutualism theory: Possible mechanisms for the delayed chronic wound healing process.

Skin microbial flora was believed to can implicate skin health, and many recent reports point out a close linkage between the dysbiosis of the microbiome with the disease. Changes of microbiota, including diversity, species, and abundance, have been demonstrated in disease states, and it was believed the changes may cause infection and chronicity of the debilitating wounds. And it was been found a reverse of the dysbiosis after the effective treatment, but it failed to find a positive effect of antibiotic therapy on skin disease without significant clinical infection. The microbiomes were compared to the 'second gene reservoir', and indicated that their co-existing with the human being is a result of co-evolution. The current studies have shown that the microbial community on the skin surface should have an ideal optimal state, which can effectively regulate the immune tolerance and help to avoid the invasion of external pathogenic bacteria, then the body can be in a relatively healthy state. In this paper, we hypothesized that failing to maintain the harmonious relationship between microbes and human beings is the reason we suffering from most skin diseases, including chronic non-healing wounds. Thus, the dysbiosis of skin microbiota theory can help us better understand the mechanism of wound formation and problems encountered in wound treatment.

Nonselective alpha-/beta- AR antagonists can inhibit pericyte proliferation, migration, and secretion in vitro.

It has been reported that the beta-adrenergic receptor blocker (propranolol) and the a-adrenergic receptor (AR) blocker (phentolamine) both can inhibit human endothelial cell (EC) angiogenesis in vitro. However, it is unknown whether this inhibition also acts on pericytes. The present study aimed to determine how pericytes react to treatment with an a-/ß- AR blocker. In the study, cell proliferation assays and scratch assay were performed to assess the effect of phentolamine or propranolol on cell proliferation and migration. Western blot and ELISA were employed to determine changes in VEGF-A and Ang-1 expression levels. The results indicated that the nonselective a-/ß- AR blocker inhibited the proliferation, migration, and secretion of pericytes. The use of the nonselective a-/ß- AR blocker might have an impact on vascularization and vascular maturation. Our research suggests the rational use of nonselective a-/ß- AR blockers to treat angiogenesis-dependent diseases.

Platelet sonicates activate hair follicle stem cells and mediate enhanced hair follicle regeneration.

An increasing number of studies show that platelet-rich plasma (PRP) is effective for androgenic alopecia (AGA). However, the underlying cellular and molecular mechanisms along with its effect on hair follicle stem cells are poorly understood. In this study, we designed to induce platelets in PRP to release factors by calcium chloride (PC) or by sonication where platelet lysates (PS) or the supernatants of platelet lysate (PSS) were used to evaluate their effect on the hair follicle activation and regeneration. We found that PSS and PS exhibited a superior effect in activating telogen hair follicles than PC. In addition, PSS injection into the skin activated quiescent hair follicles and induced K15+ hair follicle stem cell proliferation in K14-H2B-GFP mice. Moreover, PSS promoted skin-derived precursor (SKP) survival in vitro and enhanced hair follicle formation in vivo. In consistence, protein array analysis of different PRP preparations revealed that PSS contained higher levels of 16 growth factors (out of 41 factors analysed) than PC, many of them have been known to promote hair follicle regeneration. Thus, our data indicate that sonicated PRP promotes hair follicle stem cell activation and de novo hair follicle regeneration.

Microbiome Imbalances: An Overlooked Potential Mechanism in Chronic Nonhealing Wounds.

Chronic nonhealing wounds are a severe burden to health care systems worldwide, causing millions of patients to have lengthy hospital stays, high health care costs, periods of unemployment, and reduced quality of life. Moreover, treating chronic nonhealing wounds effectively and reasonably in countries with limited medical resources can be extremely challenging. With many outstanding questions surrounding chronic nonhealing wounds, in this review, we offer changes to the microbiome as a potentially ignored mechanism important in the formation and treatment of chronic wounds. Our analysis helps bring a whole new understanding to wound formation and healing and provides a potential breakthrough in the treatment of chronic nonhealing wounds in the future.

Effects of Platelet-Rich Plasma on Fat and Nanofat Survival: An Experimental Study on Mice.

BACKGROUND: Nanofat and fat graft survival is an important clinical problem. The authors of this study investigated whether PRP has an impact on fat and nanofat graft survival and vascularization in a mouse model. MATERIALS AND METHODS: Fat was harvested from a 50-year-old healthy woman by vacuum suction, and nanofat was obtained by emulsification and centrifugation procedures. PRP was collected after two rounds of centrifugation from an autologous blood sample. Twenty male nude mice were divided into four treatment groups: PRP/nanofat, PRP/fat, saline/nanofat and saline/fat. After 1 month and 3 months, the grafts were extracted and weighed. The microstructure of the fat and nanofat was examined with a scanning electron microscope. HE and immunohistochemical staining was applied to observe neovascularization. Western blot analysis was used to analyse the expression of CD31 and VEGF. RESULTS: In fat tissue, fat cells had normal connections; the fat structure was complete and fibre networks were visible. In nanofat, the extracellular matrix vascular components were visible and their structures were intact. At 1 month and 3 months, the graft weights in the PRP/fat group were significantly higher than those in the other groups. Further, a higher degree of neovascularization was observed in the PRP/nanofat group, and the expression of CD31 and VEGF in the PRP/nanofat group was higher than that in the other groups. CONCLUSION: PRP can promote nanofat and fat graft survival and vascularization. NO LEVEL ASSIGNED: 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 .

[EFFECTIVENESS OF DIFFERENT FLAPS FOR REPAIR OF SEVERE PALM SCAR CONTRACTURE DEFORMITY].

OBJECTIVE: To evaluate the effectiveness of different flaps for repair of severe palm scar contracture deformity. METHODS: Between February 2013 and March 2015, thirteen cases of severe palm scar contracture deformity were included in the retrospective review. There were 10 males and 3 females, aged from 14 to 54 years (mean, 39 years). The causes included burn in 9 cases, hot-crush injury in 2 cases, chemical burn in 1 case, and electric burn in 1 case. The disease duration was 6 months to 6 years (mean, 2.3 years). After excising scar, releasing contracture and interrupting adherent muscle and tendon, the soft tissues and skin defects ranged from 6.0 cm x 4.5 cm to 17.0 cm x 7.5 cm. The radial artery retrograde island flap was used in 2 cases, the pedicled abdominal flaps in 4 cases, the thoracodorsal artery perforator flap in 2 cases, the anterolateral thigh flap in 1 case, and the scapular free flap in 4 cases. The size of flap ranged from 6.0 cm x 4.5 cm to 17.0 cm x 7.5 cm. RESULTS: All flaps survived well. Venous thrombosis of the pedicled abdominal flaps occurred in 1 case, which was cured after dressing change, and healing by first intention was obtained in the others. The mean follow-up time was 8 months (range, 6-14 months). Eight cases underwent operation for 1-3 times to make the flap thinner. At last follow-up, the flaps had good color, and the results of appearance and function were satisfactory. CONCLUSION: Severe palm scar contracture deformity can be effectively repaired by proper application of different flaps.

Paclitaxel and Tacrolimus Coencapsulated Polymeric Micelles That Enhance the Therapeutic Effect of Drug-Resistant Ovarian Cancer.

The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating multidrug resistance in tumors has attracted increasing attention. However, the poor water solubility of some anticancer drugs restricted their clinical application. In this work, we prepared poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles as a codelivery system to load the chemotherapy drug paclitaxel (PTX) and the multidrug-resistant reversing agent tacrolimus (FK506). The PTX- and FK506-coloaded MPEG-PCL micelles (P-F/M) were prepared by a one-step solid dispersion method without any surfactants, toxic organic solvent, or severe experimental conditions. P-F/M had small particle size (28.7 ± 3.2 nm) and high encapsulation efficiency (99.3 ± 0.5%). Compared with A2780s cells (PTX-sensitive human ovarian cancer cells), P-F/M showed a stronger cytotoxicity and an improving intracellular drug concentration of PTX than PTX-loaded micelles (PTX/M) in A2780/T cells (PTX-resistant human ovarian cancer cells). Furthermore, a P-F/M codelivery system showed a more significant G2/M arrest and apoptosis induction effects, as well as activating apoptosis protein signaling pathway, in A2780/T cells than in A2780s cells. In summary, the results suggested that the codelivery micelles of PTX and FK506 may serve as a potential candidates against MDR human ovarian cancer.