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Face-lift surgery is the most crucial and constantly evolving technique of facial rejuvenation. Periodic reviews synthesizing the latest face-lift techniques may help surgeons sharpen their surgical procedures.A literature search was conducted of the PubMed databases using the search term "face lift" and "rhytidectomy." Articles reporting rhytidectomy of the forehead/brow, midface, lower face, and neck were included. Sixty-nine articles were selected after independent screening by three of the authors. The Oxford Centre for Evidence-based Medicine scale was used for evaluating evidence level.Of the 69 candidate articles, 10 studies (15%) reported techniques of neck lifting; 10 studies (15%) introduced techniques of endoscopic brow lifting; 7 studies (10%) pertained to brow lifting without endoscopic techniques. The most frequently reported locations of rhytidectomy were the brow/forehead (20%), neck (19%), and face-neck (17%). Additionally, articles regarding Asian face-lifts (14%) have been increasing. The evidence level of the articles was generally low, with only 10 articles assessed as level 1-3 with 59 articles as level 4-5.Face-lift articles with high-level evidence are still lacking. Prominently, forehead lifting and neck lifting have become upward trends of rhytidectomy in recent years, and the techniques of short-scar face-lift have been more valued.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 .

Regressive changes in epithelial stem cells underlie mammalian skin aging, but the driving mechanisms are not well understood. Here, we report that mouse skin hair follicle stem cell (HFSC) aging is initiated by their intrinsic upregulation of miR-31, a microRNA that can be induced by physical injury or genotoxic stress and is also strongly upregulated in aged human skin epithelium. Using transgenic and conditional knockout mouse models plus a lineage-tracing technique, we show that miR-31 acts as a key driver of HFSC aging by directly targeting Clock, a core circadian clock gene whose deregulation activates a MAPK/ERK cascade to induce HFSC depletion via transepidermal elimination. Notably, blocking this pathway by either conditional miR-31 ablation or clinically approved MAPK/ERK inhibitors provides safe and effective protection against skin aging, enlightening a promising therapeutic avenue for treating skin aging and other genotoxic stress-induced skin conditions such as radiodermatitis. Changes in hair and skin can be the most obvious and earliest signs of aging. The authors report that skin and hair follicle stem cell (HFSC) aging is driven by stress-induced upregulation of miR-31, which targets Clock to activate MAPK/ERK and deplete HFSCs via transepidermal elimination. Blocking the pathway with MAPK/ERK inhibitors protects against skin aging.

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The ankle and heel are challenging regions to reconstruct functionally. Here, we explored the feasibility and clinical outcomes of a modified anterior tibial artery perforator-pedicled propeller flap for the repair of soft-tissue defects of the ankle and heel. Between January 2013 and December 2015, 12 patients with soft-tissue defects of the ankle and/or heel underwent reconstructive surgery that included our flap technique. The flaps measured 20 × 8 cm to 7 × 4 cm. A hand-held Doppler was used to identify a proper constant perforator in the distal ankle. In each case, the base of the flap was well preserved. The flap was transposed (180° rotation) to reach and cover the defect. The average follow-up time was 13 months (10–28 months). We observed good texture matches and contour in all of the flaps. All patients could walk and wear normal footwear. All but one flap survived completely without complications. Partial loss was observed in one patient, and the necrotic region was healed with secondary intention. Our modified anterior tibial artery free-style perforator-pedicled propeller flap provides a novel option for functional ankle and heel reconstruction. Level IV.

Fibroblasts (Fbs) are critical to hypertrophic scar (HTS) formation and were recently shown to be highly heterogeneous. However, Fb heterogeneity in HTSs has not been fully elucidated. In this study, we observed an increased fraction of CD39+ Fbs in HTS after screening four Fb subtypes (CD26+, CD36+, FAP+, and CD39+). CD39+ Fbs, enriched in the upper dermis, were positively correlated with scar severity. The transcriptional analysis of CD39+ and CD39– Fbs sorted from HTS revealed that IL-11 was more highly expressed in CD39+ Fbs. We then showed that IL-11 was upregulated in HTSs and that its expression was induced by TGFβ1 in vitro. TGFβ1 also stimulated the expression of CD39 at the transcriptional and protein levels, mediating the maintenance of the CD39+ phenotype. Furthermore, IL-11 facilitated myofibroblast activation and extracellular matrix production in both CD39+ and CD39– Fbs. Interestingly, CD39+ Fbs secreted more IL-11 on TGFβ1 treatment and were less responsive to IL-11 than CD39– Fbs. Notably, a CD39 inhibitor effectively reduced stretch-induced scar formation and attenuated bleomycin-induced skin fibrosis, suggesting an antiscarring approach by targeting CD39+ Fbs.

Fibroblasts (Fbs) are critical to hypertrophic scar (HTS) formation and were recently shown to be highly heterogeneous. However, Fb heterogeneity in HTSs has not been fully elucidated. In this study, we observed an increased fraction of CD39

Background LEA proteins are widely distributed in the plant and animal kingdoms, as well as in micro-organisms. LEA genes make up a large family and function in plant protection against a variety of adverse conditions. Results Bioinformatics approaches were adopted to identify LEA genes in the flax genome. In total, we found 50 LEA genes in the genome. We also conducted analyses of the physicochemical parameters and subcellular location of the genes and generated a phylogenetic tree. LuLEA genes were unevenly mapped among 15 flax chromosomes and 90% of the genes had less than two introns. Expression profiles of LuLEA showed that most LuLEA genes were expressed at a late stage of seed development. Functionally, the LuLEA1 gene reduced seed size and fatty acid contents in LuLEA1-overexpressed transgenic Arabidopsis lines. Conclusion Our study adds valuable knowledge about LEA genes in flax which can be used to improve related genes of seed development.

BackgroundGenetically modified (GM) soybeans provide a huge amount of food for human consumption and animal feed. However, the possibility of unexpected effects of transgenesis has increased food safety concerns. High-throughput sequencing profiling provides a powerful approach to directly evaluate unintended effects caused by foreign genes.ResultsIn this study, we performed transcriptomic analyses to evaluate differentially expressed genes (DEGs) in individual soybean tissues, including cotyledon (C), germ (G), hypocotyl (H), and radicle (R), instead of using the whole seed, from four GM and three non-GM soybean lines. A total of 3,351 DEGs were identified among the three non-GM soybean lines. When the GM lines were compared with their non-GM parents, 1,836 to 4,551 DEGs were identified. Furthermore, Gene Ontology (GO) analysis of the DEGs showed more abundant categories of GO items (199) among non-GM lines than between GM lines and the non-GM natural varieties (166). Results of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that most KEGG pathways were the same for the two types of comparisons.ConclusionsThe study successfully employed RNA sequencing to assess the differences in gene expression among four tissues of seven soybean varieties, and the results suggest that transgenes do not induce massive transcriptomic alterations in transgenic soybeans compared with those that exist among natural varieties. This work thus provides important support for safety evaluation of genetically modified soybeans based on seed tissues.

Peripheral nerve injury (PNI) is encountered relatively commonly in the clinic and often results in long-term functional deficits. Research to develop methods to improve regeneration following nerve injury is ongoing. Numerous studies have shown that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury; however, the mechanism is unclear. Autophagy, a highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs), play important roles in regeneration after PNI. In the present study, we explored the effect and mechanism of exosomes produced by adipose-derived stem cells (ADSC-Exos) on autophagy of SCs in PNI, as well as their effect on the regeneration of the nerve myelin sheath. The levels of autophagy and the expression of karyopherin subunit alpha 2 (Kpna2) in SCs increased markedly after the sciatic nerve was injured in SCs (SNI-SCs). The enhanced autophagy and the upregulated Kpna2 in SNI-SCs were inhibited after treatment with ADSC-Exos in vivo and in vitro. The effect of ADSC-Exos on inhibiting SC autophagy was blocked by overexpression of Kpna2 in SNI-SCs. Using quantitative real-time reverse transcription PCR, ADSC-Exos were demonstrated to contain a large amount of miRNA-26b, which was predicted to regulate Kpna2 on the TargetScan website. The effect of ADSC-Exos on inhibiting SCs autophagy was blocked after the silencing of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of the myelin sheath by inhibiting SC autophagy in rat SNI models. In conclusion, our results indicated that ADSC-Exos promote the regeneration of the myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b downregulation of Kpna2.

Maintaining the length, rigidity, and appearance of a reconstructed phallus in the long term has been challenging for phalloplasty and may depend on choosing the optimal implanted stiffener. The aim of this study was to determine the best type of stiffener for a reconstructed phallus regarding aesthetic and functional parameters.From 1987 to 2018, 376 individuals underwent phalloplasty at a single institution of which 81 met the following inclusion criteria: biological male gender, age between 18 and 60 years, radial forearm flap for tube-within-a-tube phalloplasty with rib cartilage and secondary glans sculpting and unimpaired urination preoperatively. Those were divided into three groups with regard to different types of autologous rib cartilage stiffener. A group with a cartilage strip, T-shaped cartilage, and mushroom-shaped cartilage group were evaluated regarding preserved length and aesthetic features of the phallus during a minimum period of 12 months. The rib cartilage length in the phallus was 10.5 cm in all groups.The length of the phallus was 10.8 ± 0.5 cm in the cartilage strip group, 11.3 ± 0.3 cm in the T-shaped cartilage group and 11.3 ± 0.3 cm in the mushroom-shaped cartilage group at 1-year postoperatively. The aesthetic appearance score of mushroom-shaped cartilage group was 1.67 ± 0.48, significantly higher than the cartilage strip group (1.38 ± 0.50, p = 0.03) at 1 year after surgery.The mushroom-shaped autologous rib cartilage group showed superior length preservation and aesthetic appearance and appeared as the best type of stiffener for one-phase phalloplasty.

Background Microsurgical replantation has become the most favorable treatment option for scalp avulsion. However, the accurate prediction of postoperative replant viability remains challenging. Case presentation In this article, we showed that (indocyanine green angiography, ICGA) can provide a much more precise prediction of replant necrosis than conventional clinical assessment in a rare case of complete scalp avulsion with prolonged ischemia time. Conclusion Clinical assessment of replant survival may be misleading in cases of complex tissue injuries and prolonged ischemic stress. This case provides insight into the promising utility of ICGA as an important adjuvant tool to better assess tissue perfusion and viability in scalp avulsion and possibly other types of replantation.

One hour of 20-Hz continuous electrical stimulation (ES) applied at the time of injury promotes the regeneration of axons in cut peripheral nerves. A more robust enhancement of peripheral axon regeneration is achieved by 2 weeks of daily treadmill exercise. We investigated whether repeated applications of brief ES (mES) would be more effective in promoting regeneration than a single application. Sciatic nerves of C57B6 mice were cut and repaired by end-to-end anastomosis. At that time and every third day for 2 weeks, the repaired nerve was stimulated for 1 hour at 20 Hz. In controls, injured mice were either untreated or treated with ES only once. Direct muscle responses recorded from reinnervated muscles in awake animals were observed earlier both in mice treated with ES and mES than untreated controls. Their amplitudes increased progressively over the post transection study period, but the rate of this progression was increased significantly only in animals treated once with ES. Monosynaptic H reflexes recovered to pretransection levels in both untreated and singly treated mice but in the animals treated repeatedly, they were maintained at more than twice that of the same reflexes recorded prior to injury. In anatomical analyses, both excitatory and inhibitory synaptic contacts with the cell bodies of injured motoneurons, including those expressing the vesicular glutamate transporter 1 (VGLUT1), were sustained in mice treated repeatedly but not in singly treated or untreated mice. Repeated ES does not enhance the rate of restoration of functional muscle reinnervation and results in the retention of exaggerated reflexes.

Aims Recovery after peripheral nerve injury (PNI) is often difficult, and there is no optimal treatment. Schwann cells (SCs) are important for peripheral nerve regeneration, so SC‐targeting treatments have gained importance. Adipose‐derived stem cells (ADSCs) and their exosomes can promote peripheral nerve repair, but their interactions with SCs are unclear. Methods Purified SCs from sciatic nerve injury sites were harvested, and apoptosis and proliferation of SCs at post‐PNI 24 hours were analyzed. The effects of coculture with ADSCs and different concentrations of ADSC‐derived exosomes (ADSC‐Exo) were studied through in vitro experiments by flow cytometry, CCK8 assay, immunofluorescence staining, and histological analysis. The expression of the apoptosis‐related genes Bcl‐2 and Bax was also analyzed by qRT‐PCR. Results ADSC‐Exo reduced the apoptosis of SCs after PNI by upregulating the anti‐apoptotic Bcl‐2 mRNA expression and downregulating the pro‐apoptotic Bax mRNA expression. Further, it also improved the proliferation rate of SCs. This effect was confirmed by the morphological and histological findings in PNI model rats. Conclusion Our results present a novel exosome‐mediated mechanism for ADSC‐SC cross talk that reduces the apoptosis and promotes the proliferation of SCs and may have therapeutic potential in the future.

BACKGROUND Total scalp avulsion is a fairly rear but severe soft tissue injury. Even with microsurgical replantation, the survival rate is still low. In this study, the authors incorporated 2 main modifications (Halo-Vest head ring and quick hair removing) and assessed the surgical outcomes versus those of traditional replantation. METHODS: Eighteen patients were included in the study who suffered from total scalp avulsion. After consideration of the outcomes from the first 7 patients, the authors modified our surgical procedures and introduced the use of Halo-Vest head ring and quick hair removing in the treatments for the rest 11 patients. The surgical outcomes with both approaches were observed and compared, including the operation time and incidence of scalp necrosis. RESULTS: The mean debridement time was 3.5 hours in traditional treatment versus 1.68 hours in modified treatment. The mean operative time was 11.14 hours in traditional treatment versus 8.05 hours in modified treatment. After the replantation, in those 7 patients without modifications, there was 1 total scalp necrosis and 6 partial scalp necrosis. In those 11 patients with modifications, there was 1 total scalp necrosis and 1 suffered a partial scalp necrosis, while the scalp survived well in other 9 patients. Classical cases with modified or traditional methods were reported respectively. CONCLUSION The application of Halo-Vest head ring and quick hair removing provides a reliable method to treat total scalp avulsion. It is safe, technically easy and worth being widely used in the clinical application.

Background: Peripheral nerve injury is encountered quite commonly in the clinic and often results in long-term functional deficits. Investigation toward the development of methods to improve regeneration following nerve injury is ongoing. Numerous studies proved that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury, but the mechanism is not clear. Autophagy, highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs) play important roles in the regeneration of peripheral nerve injury. Methods: In this study, we explored the effect of ADSC-derived exosomes (ADSC-Exos) on the SCs autophagy and the regeneration of myelin sheath after sciatic nerve injury. Findings: The enhanced autophagy was inhibited, the up-regulated expression of KPNA2 was decreased, and the down-regulated levels of miRNA-26b was increased in injured SCs after treatment with ADSCs-Exos. Usingreal-time PCR, ADSC-Exos were shown to contained a large number of miRNA-26b. The effect of ADSC-Exos inhibiting SCs autophagy were blocked after the over-expression of KPNA2 or the silence of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of myelin sheaths of injured sciatic nerves in rats. Interpretation: Our results indicate that ADSC-Exos promote the regeneration of myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b down-regulating KPNA2. Funding Statement: This study was supported by National Key R&D Program of China (2018YFA0107500), National Natural Science Foundation of China (81572146, 31771511), Shanghai Health System Excellent Discipline Leadership Program(2017BR034)and China Postdoctoral Science Foundation (2017M623362, 2018T111131). Declaration of Interests: The authors report no conflicts of interest in this work. Ethics Approval Statement: All animal experiments met the requirements of the Ethics Committee.

OBJECTIVE: To investigate the effects of exosomes from adipose-derived stem cells (ADSCs) on peripheral nerve regeneration, and to find a new treatment for peripheral nerve injury. METHODS: Thirty-six adult Sprague Dawley (SD) rats (male or female, weighing 220-240 g) were randomly divided into 3 groups (n=12). Group A was the control group; group B was sciatic nerve injury group; group C was sciatic nerve injury combined with exosomes from ADSCs treatment group. The sciatic nerve was only exposed without injury in group A, and the sciatic nerve crush injury model was prepared in groups B and C. The SD rats in groups A and B were injected with PBS solution of 200 μL via tail veins; the SD rats in group C were injected with pure PBS solution of 200 μL containing 100 μg exosomes from ADSCs, once a week and injected for 12 weeks. At 1 week after the end of the injection, the rats were killed and the sciatic nerves were taken at the part of injury. The sciatic nerve fiber bundles were observed by HE staining; the SCs apoptosis of the sciatic nerve tissue were detected by TUNEL staining; the ultrastructure and SCs autophagy of the sciatic nerve were observed by transmission electron microscope. RESULTS: Gross observation showed that there was no obvious abnormality in the injured limbs of group A, but there were the injured limbs paralysis and muscle atrophy in groups B and C, and the degree of paralysis and muscle atrophy in group C were lighter than those in group B. HE staining showed that the perineurium of group A was regular; the perineurium of group B was irregular, and there were a lot of cell-free structures and tissue fragments in group B; the perineurium of group C was more complete, and significantly well than that of group B. TUNEL staining showed that the SCs apoptosis was significantly increased in groups B and C than in group A, in group B than in group C (P

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells.

Increasing evidence has shown that aberrant miRNAs contribute to the development and progression of human melanoma. Previous studies have shown that miR-125b functions as a suppressor in malignant melanoma. However, the molecular function and mechanism by which miR-125b influences melanoma growth and invasion are still unclear. In this study, we aimed to investigate the role of miR-125b in melanoma progression and metastasis. We found that miR-125b expression is significantly downregulated in primary melanoma, and an even greater downregulation was observed in metastatic invasion. Restored expression of miR-125b in melanoma suppressed cell proliferation and invasion both in vitro and in vivo. Furthermore, our findings demonstrate that upregulating miR-125b significantly inhibits malignant phenotypes by repressing the expression of integrin alpha9 (ITGA9). Finally, our data reveal that upregulated expression of ITGA9 in melanoma tissues is inversely associated with miR-125b levels. Together, our results demonstrate that upregulation of ITGA9 in response to the decrease in miR-125b in metastatic melanoma is responsible for melanoma tumor cell migration and invasion.

Following peripheral nerve injury, synapses are withdrawn from axotomized motoneurons. Moderate daily treadmill exercise, which promotes axon regeneration of cut peripheral nerves, also influences this synaptic stripping. Different exercise protocols are required to promote axon regeneration in male and female animals, but the sex requirements for an effect of exercise on synaptic stripping are unknown. In male and female C57BL/6 mice, the sciatic nerve was transected in the mid-thigh. Mice were then exercised five days per week for two weeks, beginning on the third post-transection day. Half of the exercised mice were trained by walking slowly (10 M/min) on a level treadmill for one hour per day (continuous training). Other mice were interval trained; four short (two min) sprints at 20 M/min separated by five minute rest periods. A third group was untrained. The extent of synaptic contacts made by structures immunoreactive to vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 onto axotomized motoneurons was studied in confocal images of retrogradely labeled cells. Both types of presumed synaptic contacts were reduced markedly in unexercised mice following nerve transection, relative to intact mice. No significant reduction was found in continuous trained males or interval trained females. Reductions in these contacts in interval trained males and continuous trained females were identical to that observed in untrained mice. Treatments with the anti-androgen, flutamide, blocked the effect of sex-appropriate exercise on synaptic contacts in both males and females. Moderate daily exercise has a potent effect on synaptic inputs to axotomized motoneurons. Successful effects of exercise have different requirements in males and females, but require androgen receptor signaling in both sexes.