Relieving Macrophage Dysfunction by Inhibiting SREBP2 Activity: A Hypoxic Mesenchymal Stem Cells-Derived Exosomes Loaded Multifunctional Hydrogel for Accelerated Diabetic Wound Healing.

Macrophage dysfunction is one of the primary factors leading to the delayed healing of diabetic wounds. Hypoxic bone marrow mesenchymal stem cells-derived exosomes (hyBMSC-Exos) have been shown to play an active role in regulating cellular function through the carried microRNAs. However, the administration of hyBMSC-Exos alone in diabetic wounds usually brings little effect, because the exosomes are inherently unstable and have a short retention time at the wounds. In this study, a multifunctional hydrogel based on gallic acid (GA) conjugated chitosan (Chi-GA) and partially oxidized hyaluronic acid (OHA) is prepared for sustained release of hyBMSC-Exos. The hydrogel not only exhibits needs-satisfying physicochemical properties, but also displays outstanding biological performances such as low hemolysis rate, strong antibacterial capacity, great antioxidant ability, and excellent biocompatibility. It has the ability to boost the stability of hyBMSC-Exos, leading to a continuous and gradual release of the exosomes at wound locations, ultimately enhancing the exosomes' uptake efficiency by target cells. Most importantly, hyBMSC-Exos loaded hydrogel shows an excellent ability to promote diabetic wound healing by regulating macrophage polarization toward M2 phenotype. This may be because exosomal miR-4645-5p and antioxidant property of the hydrogel synergistically inhibit SREBP2 activity in macrophages. This study presents a productive approach for managing diabetic wounds.

Soluble microneedle patch with photothermal and NO-release properties for painless and precise treatment of ischemic perforator flaps.

Skin necrosis is the most serious complication of flap plastic surgery, which means the failure of the operation. Systemic administration rarely benefits the local area and can lead to side effects, while topical administration has poor permeability due to the skin barrier function. Currently, few of these common medical interventions can totally respond to the blood supply of the skin after surgery. Herein, a soluble microneedle (MN) patch made of hyaluronic acid was used to target the ischemic area in a painless and precise manner for transdermal drug delivery. Based on the important role of nitric oxide (NO) in angiogenesis, the thermosensitive NO donor (BNN6) and gold nanorods (GNRs) acting as photothermal agents were introduced into the microneedles (MNs). The hyperthermia induced by GNRs under near infrared (NIR, 808 nm) irradiation could enhance the penetration of drugs and facilitate NO release from BNN6. A series of corresponding experiments proved that the system played a significant promotion role in vascular regeneration, providing a painless, precise and NO-assisted treatment method for the ischemic perforator flaps.

Extracellular vesicle-enclosed miR-486-5p mediates wound healing with adipose-derived stem cells by promoting angiogenesis.

Adipose-derived stem cells (ASC) are said to have a pivotal role in wound healing. Specifically, ASC-secreted extracellular vesicles (EV) carry diverse cargos such as microRNAs (miRNAs) to participate in the ASC-based therapies. Considering its effects, we aimed to investigate the role of ASC-EVs in the cutaneous wound healing accompanied with the study on the specific cargo-medicated effects on wound healing. Two full-thickness excisional skin wounds were created on mouse dorsum, and wound healing was recorded at the indicated time points followed by histological analysis and immunofluorescence staining for CD31 and α-SMA. Human skin fibroblasts (HSFs) and human microvascular endothelial cells (HMECs) were co-cultured with EVs isolated from ASC (ASC-EVs), respectively, followed by the evaluation of their viability and mobility using CCK-8, scratch test and transwell migration assays. Matrigel-based angiogenesis assays were performed to evaluate vessel-like tube formation by HMECs in vitro. ASC-EVs accelerated the healing of full-thickness skin wounds, increased re-epithelialization and reduced scar thickness whilst enhanced collagen synthesis and angiogenesis in murine models. However, miR-486-5p antagomir abrogated the ASC-EVs-induced effects. Intriguingly, miR-486-5p was found to be highly enriched in ASC-EVs, exhibiting an increase in viability and mobility of HSFs and HMECs and enhanced the angiogenic activities of HMECs. Notably, we also demonstrated that ASC-EVs-secreted miR-486-5p achieved the aforesaid effects through its target gene Sp5. Hence, our results suggest that miR-486-5p released by ASC-EVs could be a critical mediator to develop an ASC-based therapeutic strategy for wound healing.

[Clinical application of modified kite flap in treatment of divided nevus of lateral canthus].

OBJECTIVE: To investigate the effectiveness of modified kite flap in repair of soft tissue defect after divided nevus of lateral canthus excision. METHODS: Between October 2010 and April 2018, 20 children (20 eyes) with divided nevus of lateral canthus were admitted. There were 13 boys and 7 girls, with an average age of 7.9 years (mean, 4-14 years). There were 11 cases of moderate range lesions (maximum diameter, 1.5-2.0 cm) and 9 cases of small range lesions (maximum diameter, <1.5 cm). After excising the divided nevus of lateral canthus, the area of soft tissue defect ranged from 0.72 to 3.23 cm2。The modified kite flap was used to reconstruct the structure and shape of lateral canthus. RESULTS: There were 16 cases of mixed nevus and 4 cases of intradermal nevus. The flaps survived and the incisions healed by the first intention. The patients were followed up 12-22 months (mean, 13.6 months). There was no malformation, valgus, exposure keratitis, or obvious scar. No malignant transformation occurred or nevus recurred during follow-up. At last follow-up, the effectiveness was rated as excellent in 16 cases, good in 3 cases, and poor in 1 case. CONCLUSION: The modified kite flap can repair the soft tissue defect after excising the divided nevus of lateral canthus, and obtain the good appearance and function of lateral canthus.

[The application of modified rhomboid flap in repairing facial skin and soft tissue defect].

Objective: To explore the effectiveness of modified rhomboid flap for repairing facial skin and soft tissue defect. Methods: Between January 2016 and May 2018, 23 patients with facial skin and soft defect were repaired by the modified rhomboid flap. There were 10 males and 13 females with the median age of 27 years (range, 11-72 years). The primary tumor included pigmented nevus in 18 cases, basal cell carcinoma in 4 cases, and squamous cell carcinoma in 1 case. The defect location was nose in 8 cases, cheek in 4 cases, malar in 6 cases, forehead in 2 cases, and upper lip in 3 cases. The defect ranged from 0.8 cm×0.8 cm to 3.9 cm×3.9 cm. According to the location and size of facial tumors, the resection area of square lesions was designed. According to the mobility of surrounding tissues and the direction of dermatoglyphic lines, the rhomboid flaps with an angle of 45-60° was designed to repair the defect by tension-free rotation. Results: All the flaps survived and the incision healed by first intension. All patients were followed up 3-15 months (mean, 7.3 months). During follow-up, no tumor reoccurred; the color and texture of the flaps were similar with surrounding tissue. There was no obvious scar hyperplasia, nor traction of adjacent normal tissues, and patients were satisfied with the appearance. Conclusion: The application of modified rhomboid flaps in repairing facial skin and soft tissue defects caused by resection of round facial tumor has the advantages of flexible design, simple manipulation, and less trauma.

[CLINICAL STUDY ON ZYGOMATIC SPINDLE-SHAPED OSTEOTOMY AND INTERNAL PUSH OF TITANIUM SCREW ANCHOR IN TREATMENT OF PROMINENT MALAR].

OBJECTIVE: To explore the effectiveness of the zygomatic spindle-shaped osteotomy and internal push of titanium screw anchor for prominent malar. METHODS: Between July 2011 and January 2015, 58 patients with prominent malar underwent zygomatic spindle-shaped osteotomy and internal push of titanium screw anchor. There were 3 males and 55 females, aged 18-33 years (mean, 23 years). They had congenital bilateral prominent malar. Preoperative anteroposterior, lateral, supine position, 45" oblique photographs of the face were taken, three-dimensional CT reconstruction of face was performed. Simple prominent malar was observed in 30 cases, and prominent malar and zygomatic arch in 28 cases; zygomatic bone and zygomatic arch were symmetrical in 51 cases, and asymmetrical in 7 cases. RESULTS: All patients obtained stage I incision healing after operation, without infection or hematoma. Numbness of the upper lip occurred in 2 cases, limitation of mouth opening in 1 case, and nasolabial fold deepening in 1 case, which recovered spontaneously after 3 months. Fifty-eight cases were followed up 6-12 months (mean, 10 months). Zygomatic narrow spacing was 10.6-13.9 mm (mean, 11.2 mm). No ptosis of facial soft tissue, zygomatic step, facial nerve injury, raising eyebrow, dysfunction of eyes closure, or temporomandibular joint disorder syndrome occurred. Good bone healing was obtained, zygomatic facial sensation had no obvious abnormality, all patients were satisfied with the improvement of appearance. CONCLUSION: Zygomatic spindle-shaped osteotomy and internal push titanium screw anchor can effectively reduce the cheekbones, and maintain the natural curve of zygomatic body and zygomatic arch. Because of simple operation, less complications, and excellent results, it is an ideal plasty.

Prognostic value of cancer stem cell marker CD133 expression in esophageal carcinoma: A meta-analysis.

CD133 has been identified as a putative neoplastic stem cell marker in esophageal carcinoma. However, the prognostic value of CD133 overexpression in patients with esophageal carcinoma remains controversial. A meta-analysis of previous studies was performed, in order to assess the association of CD133 overexpression with the clinicopathological characteristics of esophageal carcinoma patients. A total of 7 studies, including 538 patients, were subjected to the final analysis. Our results indicated that a positive CD133 expression was significantly associated with lymph node metastasis [odds ratio (OR)=3.09, 95% confidence interval (CI): 1.93-4.95; P<0.00001], clinical stage (OR=4.26, 95% CI: 1.55-11.73; P=0.005) and histopathological grade (OR=2.40, 95% CI: 1.16-4.94; P=0.02). There was no statistically significant association of CD133 with depth of invasion (OR=1.89, 95% CI: 0.42-8.43; P=0.41). Based on the results of this study, we concluded that CD133 is an efficient prognostic factor in esophageal carcinoma. Higher CD133 expression is significantly associated with lymph node metastasis, clinical stage and histopathological grade.

Cell-assisted lipotransfer in the clinical treatment of facial soft tissue deformity.

Cosmetic surgeons have experimented with a variety of substances to improve soft tissue deformities of the face. Autologous fat grafting provides significant advantages over other modalities because it leaves no scar, is easy to use and is well tolerated by most patients. Autologous fat grafting has become one of the most popular techniques in the field of facial plastic surgery. Unfortunately, there are still two major problems affecting survival rate and development: revascularization after transplantion; and cell reservation proliferation and survival. Since Zuk and Yosra developed a technology based on adipose-derived stem cells and cell-assisted lipotrophy, researchers have hoped that this technology would promote the survival and reduce the absorption of grafted fat cells. Autologous adipose-derived stem cells may have great potential in skin repair applications, aged skin rejuvenation and other aging-related skin lesion treatments. Recently, the study of adipose-derived stem cells has gained increased attention. More researchers have started to adopt this technology in the clinical treatment of facial soft tissue deformity. The present article reviews the history of facial soft tissue augmentation and the advent of adipose-derived stem cells in the area of the clinical treatment of facial soft tissue deformity.

Les plasticiens ont mis diverses substances à l'essai pour corriger les malformations des tissus mous de la face. La greffe de graisse autologue comporte d'importants avantages par rapport aux autres modalités, car elle ne laisse aucune cicatrice, est facile à utiliser et est bien tolérée par la plupart des patients. C'est désormais l'une des techniques les plus populaires en chirurgie plastique de la face. Malheureusement, deux grands problèmes influent encore sur le taux de survie et le développement : la revascularisation après la greffe ainsi que l'inventaire, la prolifération et la survie des cellules. Depuis que Zuk et Yosra ont mis au point une technologie qui repose sur les cellules souches adipeuses et la lipotrophie cellulaire, les chercheurs espèrent que cette technologie permettra de promouvoir la survie et de réduire l'absorption des cellules adipeuses greffées. Les cellules souches adipeuses autologues ont peut-être plus de potentiel pour les applications de réparation cutanée, le rajeunissement de la peau vieillissante et d'autres traitements des lésions cutanées liées au vieillissement. L'étude des cellules souches adipeuses a commencé à susciter l'attention. Plus de chercheurs ont commencé à adopter cette technologie pour le traitement clinique des malformations des tissus mous de la face. L'histoire de l'augmentation des tissus mous de la face et l'utilisation des cellules souches adipeuses pour le traitement clinique des malformations s'y rapportant sont analysées dans le présent article.

Prognostic value of tumor-infiltrating FoxP3+ T cells in gastrointestinal cancers: a meta analysis.

PURPOSE: Tumor-infiltrating FoxP3+ T cells have been reported in various human tumors, which impaired cell-mediated immunity and promoted disease progression. However, its prognostic value for survival in patients with different gastrointestinal cancers [hepatocellular carcinoma (HCC), colorectal cancer (CRC), gastric cancer (GC)] remains controversial. METHODS: Relevant literature was searched using PubMed, Embase, Cochrane, Ovid Medline and Chinese wanfang databases. A meta-analysis was conducted to estimate pooled survival and recurrence ratios. The odds ratio (OR) and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: For HCC and GC, the overall survival at 1, 3 and 5-year of high FoxP3+ T cells infiltration patients were lower than low FoxP3+ T cells infiltration patients (P<0.05). The recurrences at 1, 3 and 5-year of high FoxP3+ T cells infiltration patients were higher than low FoxP3+ T cells infiltration patients (P<0.001). But for CRC, the overall survival at 1, 3 and 5-year of high FoxP3+ T cells infiltration patients were higher than low FoxP3+ T cells infiltration patients (P<0.001). There were no differences in 1, 3 and 5-year recurrences between high and low FoxP3+ T cells infiltration patients (P>0.05). CONCLUSIONS: Our findings suggested that tumor-infiltrating FoxP3+ T cells were a factor for a poor prognosis for HCC and GC, but a good prognosis for CRC.

[Treatment of auricular keloids with surgery and intralesional injection of compound betamethasone].

OBJECTIVE: To investigate the treatment of auricular keloid with dinuclear surgery and intralesional injection of compound Betamethasone. METHODS: From Jan. 2008 to Jan. 2012, a total of 186 cases of ear keloid were treated by surgery only (22 cases), or intralesional injection of compound Betamethasone (34 cases), or combined dinuclear surgery with compound Betamethasone (130 cases). All the patients were followed up for one year. SPSS 16.0 software was used for statistical processing and analysis, and GraphPad inspection method for inspection. RESULTS: The effective rate was 54.55% (12/ 22) in surgery group and 55.88% (19/34)in injection group. The recurrence was obvious in injection group during the follow-up period. The effective rate was as high as 96.92% (126/130) in combined group with recurrence in 4 cases, which was significantly higher than that in other 2 groups (P < 0. 01). CONCLUSION: Combined dinuclear surgery and compound Betamethasone injection has a good therapeutic effect on auricular keloids.

[Progress of autologous fat grafting in clinical applications of the face].

OBJECTIVE: To review the progress of autologous fat grafting of the face and outline different arguments in this field. METHODS: Recent literature concerning autologous fat grafting of the face was reviewed and analyzed. RESULTS: The applications and techniques for autologous fat grafting have been matured increasingly. It not only can adjust the proportion of facial contours, restore tissue volume, but also can improve the local skin texture. Reliable clinical results have achieved in facial augmentation and rejuvenation. Although there are arguments about donor site, harvesting technique, processing technique, and grafting technique, the basic principle is the same. CONCLUSION: From the perspective of evidence-based medicine, clinicians are rich in clinical experience, but objective evidence is insufficient. So further researches should be carried to look for scientific evidences.