Isolation of the Stromal Vascular Fraction Using a New Protocol with All Clinical-Grade Drugs: From Basic Study to Clinical Application.

OBJECTIVE: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. MATERIALS AND METHODS: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. RESULTS: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. CONCLUSION: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. TRIAL REGISTRATION: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Angiogenesis modulation-mediated inhibitory effects of tacrolimus on hypertrophic scar formation.

Hypertrophic scar (HS) is a fibroproliferative disorder that causes cosmetic as well as functional problems; however, to our knowledge, there is no satisfactory treatment for HS to date. Previous studies have indicated that angiogenesis plays a crucial role in HS formation; therefore, anti-angiogenetic therapies are considered effective in improving HS. Although tacrolimus (TAC) has been proven effective in preventing HS formation in vivo and in vitro, its underlying mechanism remains controversial and ambiguous. Because of its anti-angiogenic effects in other diseases, we aimed to determine whether TAC reduces HS by suppressing angiogenesis. Using a rabbit ear HS model that we developed, HS was treated once a week with normal saline, dimethyl sulfoxide, or TAC for 3 weeks. Histological evaluation indicated that TAC significantly reduced collagen deposition and microvessel density in scar tissues. Moreover, immunofluorescence staining for CD31 and vascular endothelial growth factor (VEGF)-A revealed that TAC significantly inhibited HS angiogenesis. In vitro analysis showed that TAC inhibited endothelial cell migration and tubulogenesis as well as the viability and proliferation of human umbilical vascular endothelial cells (HUVECs) and HS fibroblasts (HSFBs). Furthermore, TAC significantly downregulated the expression of the human angiogenetic factors VEGF-A, FGF-2, PDGF-ß, and TGF-ß1 in HUVECs and HSFBs. Additionally, TAC-mediated inhibition of angiogenesis decreased the gene expression of crucial fibrotic markers, including α- smooth muscle actin and collagens 1 and 3, in HSFBs. This is the first study to demonstrate the inhibitory effects of TAC on HS formation mediated by a mechanism involving the suppression of scar angiogenesis.

Enhancing Faraday and Kerr rotations based on the toroidal dipole mode in an all-dielectric magneto-optical metasurface.

The magneto-optical Faraday and Kerr effects are widely used in modern optical devices. In this Letter, we propose an all-dielectric metasurface composed of perforated magneto-optical thin films, which can support the highly confined toroidal dipole resonance and provide full overlap between the localized electromagnetic field and the thin film, and consequently enhance the magneto-optical effects to an unprecedented degree. The numerical results based on the finite element method show that the Faraday and Kerr rotations can reach -13.59° and 8.19° in the vicinity of toroidal dipole resonance, which are 21.2 and 32.8 times stronger than those in the equivalent thickness of thin films. In addition, we design an environment refractive index sensor based on the resonantly enhanced Faraday and Kerr rotations, with sensitivities of 62.96 nm/RIU and 73.16 nm/RIU, and the corresponding maximum figures of merit 132.22°/RIU and 429.45°/RIU, respectively. This work provides a new, to the best of our knowledge, strategy for enhancing the magneto-optical effects at nanoscale, and paves the way for the research and development of magneto-optical metadevices such as sensors, memories, and circuits.

Diagnosis and Management of Pseudoblepharoptosis in Eastern Asians: A Commonly Observed But Easily Overlooked Type of Blepharoptosis.

BACKGROUND: Pseudoblepharoptosis, which is characterized by ptotic eyelid appearance with normal levator function, is a common abnormality observed in Eastern Asians. Misdiagnosis of pseudoblepharoptosis may lead to inappropriate treatments and unwanted complications. Using the data obtained from a modified levator function examination, this study sought to improve the diagnosis and explore the appropriate treatment of pseudoblepharoptosis based on the typical eyelid anatomy of Eastern Asians. METHODS: This retrospective study included patients with drooping and bulky eyelids who had been preoperatively diagnosed between January 2018 and December 2018 using a modified approach. Debulking of the retro-orbicularis oculus fat and orbital septum fat and release of the ligament-like structure were performed to correct pseudoblepharoptosis without manipulating the levator muscle. The functional and aesthetic outcomes were evaluated postoperatively. RESULTS: The proposed modified approach was significantly more accurate than the traditional technique. Of the patients, 78 (84.8%) and 9 (9.8%) showed good and moderate cosmetic outcomes, respectively. The margin reflex distance 1 value significantly improved from 1.74±0.87 mm preoperatively to 4.56±0.71 mm postoperatively ( P <0.05). Moreover, 179 (97.3%) of the 184 eyelids examined achieved adequate correction. CONCLUSIONS: The modified levator function examination approach used in this study may help improve the diagnosis of pseudoblepharoptosis. Surgical intervention focused on correcting the bulky and drooping upper eyelids and orbital septum may lead to satisfactory outcomes in Eastern Asians with pseudoblepharoptosis without manipulating the levator muscle.

Performance of Quantum Heat Engines Enhanced by Adiabatic Deformation of Trapping Potential.

We present a quantum Otto engine model alternatively driven by a hot and a cold heat reservoir and consisting of two isochoric and two adiabatic strokes, where the adiabatic expansion or compression is realized by adiabatically changing the shape of the potential. Here, we show that such an adiabatic deformation may alter operation mode and enhance machine performance by increasing output work and efficiency, even with the advantage of decreasing work fluctuations. If the heat engine in the sudden limit operates under maximal power by optimizing the control parameter, the efficiency shows certain universal behavior, η*=ηC/2+ηC2/8+O(ηC3), where ηC=1-ßhr/ßcr is the Carnot efficiency, with ßhr(ßcr) being the inverse temperature of the hot (cold) reservoir. However, such efficiency under maximal power can be produced by our machine model in the regimes where the machine without adiabatic deformation can only operate as a heater or a refrigerator.

Efficiency Bounds for Minimally Nonlinear Irreversible Heat Engines with Broken Time-Reversal Symmetry.

We study the minimally nonlinear irreversible heat engines in which the time-reversal symmetry for the systems may be broken. The expressions for the power and the efficiency are derived, in which the effects of the nonlinear terms due to dissipations are included. We show that, as within the linear responses, the minimally nonlinear irreversible heat engines can enable attainment of Carnot efficiency at positive power. We also find that the Curzon-Ahlborn limit imposed on the efficiency at maximum power can be overcome if the time-reversal symmetry is broken.

"Stamp Perforation" Technique for Correction of Prominent Mandibular Angle: 10 Years of Experience in Mandibular Reshaping in Asians.

Resection of a prominent mandibular angle is commonly used in Eastern society to improve the lower one third facial proportion. Historically, this procedure had a high complication rate, such as severe bleeding, asymmetry of the angle reduction, and "second mandibular angle." A safer and more effective way of performing such procedures is needed. The aim of this study is to introduce 3 instruments, a tunable guide handpiece, milling cutter, and flywheel, which were invented by the author, as well as a related ostectomy technique for correcting prominent mandibular angles using a modified full-thickness marginal ostectomy of the mandibular corpus angle, named the "stamp perforation" technique. This technique has 4 highlights: First, it ensures a smooth symmetric contour. Second, it prevents the risks of rupture of the inferior alveolar vessel and facial artery, ensuring the safety of this approach. Third, the "stamp perforation" technique eases the removal of bone fragments, shortening the operation time. Fourth, the recovery time of patients treated with this approach is much shorter than with the traditional approaches. From January 2006 to January 2016, 1106 patients underwent the surgery to contour the prominent mandible angles, and satisfactory results were achieved. Thus, we recommend the instruments as well as the "stamp perforation" technique for correcting prominent mandibular angles, and we hope that our 10 years of experience could provide a reference for other plastic surgeons.

Performance enhancement of quantum Brayton engine via Bose-Einstein condensation.

Bose-Einstein condensation is a quintessential characteristic of Bose systems. We investigate the finite-time performance of an endoreversible quantum Brayton heat engine operating with an ideal Bose gas with a finite number of particles confined in a d-dimensional harmonic trap. The working medium of these engines may work in the condensation, noncondensation, and near-critical point regimes, respectively. We demonstrate that the existence of the phase transition during the cycle leads to enhanced engine performance by increasing power output and efficiencies corresponding to maximum power and maximum efficient power. We also show that the quantum engine working across the Bose-Einstein condensation in N-particle Bose gas outperforms an ensemble of independent single-particle heat engines. The difference in the machine performance can be explained in terms of the behavior of specific heat at constant pressure near the critical point regime.

Concentrated ultrasound-processed fat (CUPF): More than a mechanically emulsified graft.

INTRODUCTION: Autologous fat grafting is still an evolving technique. Researchers have attempted to increase the survival rate of grafts by concentrating adipose-derived stem cells (ASCs). In this study, we investigate a novel method that combines ultrasonic processing and centrifugation to generate small fat particles termed concentrated ultrasound-processed fat (CUPF) for grafting. METHODS: The standard approach for obtaining CUPF is described. The properties of processed fat, including CUPF, microfat, centrifuged fat, and nanofat, were investigated using histological observation. Comparative analyses were conducted on the cell number, viability, and immunophenotypic profile of stromal vascular fraction cells (SVFs). Cultured ASCs were evaluated for cell proliferation and adipogenic, osteogenic, and chondrogenic potential. The processed fats were transplanted and evaluated using in vivo and histological studies. RESULTS: Compared with microfat, centrifuged fat, and nanofat, CUPF had a condensed tissue content and higher concentration of viable cells in a small tissue structure and could smoothly pass through a 27-gauge cannula. In the CUPF group, SVFs were isolated in great numbers, with high viability and a high proportion of CD29- and CD105-positive cells. ASCs from the CUPF group exhibited high proliferation and multilineage differentiation potential. The grafts from the CUPF group were well preserved, and histological quantification revealed an increase in the abundance of Ki67- and CD31-positive cells in the tissue. CONCLUSIONS: Our study established a new fat processing strategy that combines ultrasonic processing and centrifugation to harvest small particle grafts named CUPF. CUPF concentrated a large number of ASCs and has great potential for regenerative therapy.

Autologous Concentrated Growth Factor Increases Skin Thickness and Area during Tissue Expansion: A Randomized Clinical Trial.

BACKGROUND: Mechanical stretching of the skin (ie, tissue expansion) could generate additional skin, but it is limited by the intrinsic growth capacity. The authors conducted a study of autologous concentrated growth factor (CGF) to promote skin regeneration by increasing skin thickness and area during tissue expansion. METHODS: A single-center randomized controlled trial was conducted from 2016 to 2019. Participants undergoing skin expansion received either CGF or saline by means of intradermal injection on the expanded skin (0.02 mL/cm 2 ), for a total of three treatments at 4-week intervals. The primary endpoint was the expanded skin thickness at 12 weeks, which was measured by ultrasound. The secondary endpoints included skin thickness at 4 and 8 weeks and surface area, expansion index, and skin texture score of the expanded skin at 12 weeks. Safety assessments, for infection symptoms and nodule formation, were assessed at 24 weeks. RESULTS: In total, 26 patients were enrolled and assigned to the CGF or control group. Compared with the control group, the CGF group had significantly increased skin thickness at 8 (control, 1.1 ± 0.1 mm; CGF, 1.4 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047) and 12 weeks (control, 1.0 ± 0.1 mm; CGF, 1.3 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047). Compared with the baseline thickness (control, 1.6 ± 0.1 mm; CGF, 1.5 ± 0.1 mm; -0.3 to 0.5 mm; P = 0.987), skin thickness was sustained in the CGF group at 8 weeks after treatment (-0.1 to 0.3 mm; P = 0.711) but decreased in the control group (0.3 to 0.7 mm; P < 0.001). At 12 weeks, the CGF group showed greater increases in surface area (control, 77.7 ± 18.5 cm 2 ; CGF, 135.0 ± 15.7 cm 2 ; 7.2 cm 2 to 107.4 cm 2 ; P = 0.027) and expansion index (control, 0.9 ± 0.1; CGF, 1.4 ± 0.2; 0.0 to 0.8; P = 0.030) than the control group. In addition, CGF-treated skin showed an improvement in texture [CGF: grade 3, n = 2 (15.8%), grade 2, n = 4 (30.7%); control: grade 3, n = 0 (0.0%), grade 2, n = 3 (23.0%)]. No severe adverse events occurred. CONCLUSION: CGF treatment increases skin thickness and area during tissue expansion, and represents a safe and effective strategy for managing skin expansion. CLINICAL RELEVANCE STATEMENT: The findings of this study indicate that it is practically feasible to improve skin regeneration by applying autologous platelet concentrate therapy for skin expansion management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.