Publications by authors named "Yori Endo"

25 Publications

  • Page 1 of 1

Lights, camera, scalpel: a lookback at 100 years of plastic surgery on the silver screen.

Eur J Plast Surg 2021 Jul 8:1-11. Epub 2021 Jul 8.

Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, 45 Francis St, Boston, MA 02115 USA.

Background: The presentation of medical topics in the cinema can greatly influence the public's understanding and perception of a medical field, with regard to the doctors and surgeons, medical diagnosis, and treatment and outcome expectations. This study aims to evaluate the representation of plastic surgery in commercial films that include a character with a link to plastic surgery, either as a patient or surgeon.

Methods: The international film databases Internet Movie Database (IMDb), The American Film Institute (AFI), and British Film Institute (BFI) were searched from 1919 to 2019 to identify feature-length films with a link to plastic surgery. Movies were visualized and analyzed to identify themes, and the portrayal of plastic surgery was rated negative or positive, and realistic or unrealistic.

Results: A total of 223 films were identified from 1919 to 2019, produced across 19 countries. Various genres were identified including drama (41), comedy (25), and crime (23). A total of 172 patient characters and 57 surgeon characters were identified as major roles, and a further 102 surgeons as minor roles. Disparities were noted in presentation of surgeons, both in terms of race and gender, with the vast majority of surgeons being white and male. In total only 11 female surgeons were portrayed and only one black surgeon. Thirteen themes emerged: face transplantation, crime, future society, surgeon mental status, body dysmorphic disorder, vanity, anti-aging, race, reconstructive surgery, deformity, scarring, burns, and gender transitioning. The majority of films (146/223) provide an unrealistic view of plastic surgery, painted under a negative light (80/146). Only 20 films provide a positive realistic image (24/77).

Conclusions: There exists a complicated relationship between plastic surgery and its representation on film. Surgical and aesthetic interventions are portrayed unrealistically, with surgeons and patients presented negatively, perpetuating stigma, particularly with regard to cosmetic surgery. Cinema is also characterized by lack of representation of female and non-white surgeons. Recruitment of surgeons as technical advisors would help present a more realistic, representative view, without necessarily sacrificing creativity.Level of evidence: Not ratable.
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http://dx.doi.org/10.1007/s00238-021-01834-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263318PMC
July 2021

Muscle Cryoinjury and Quantification of Regenerating Myofibers in Mice.

Bio Protoc 2021 Jun 5;11(11):e4036. Epub 2021 Jun 5.

Department of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

Cryoinjury, or injury due to freezing, is a method of creating reproducible, local injuries in skeletal muscle. This method allows studying the regenerative response following muscle injuries , thus enabling the evaluation of local and systemic factors that influence the processes of myofiber regeneration. Cryoinjuries are applicable to the study of various modalities of muscle injury, particularly non-traumatic and traumatic injuries, without a loss of substantial volume of muscle mass. Cryoinjury requires only simple instruments and has the advantage over other methods that the extent of the lesion can be easily adjusted and standardized according to the duration of contact with the freezing instrument. The regenerative response can be evaluated histologically by the average maturity of regenerating myofibers as indicated by the cross-sectional areas of myofibers with centrally located nuclei. Accordingly, cryoinjury is regarded as one of the most reliable and easily accessible methods for simulating muscle injuries in studies of muscle regeneration.
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http://dx.doi.org/10.21769/BioProtoc.4036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250343PMC
June 2021

Exercise-induced gene expression changes in skeletal muscle of old mice.

Genomics 2021 Sep 30;113(5):2965-2976. Epub 2021 Jun 30.

Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Harvard Stem Cell Institute, Cambridge, MA, United States. Electronic address:

Exercise is believed to be beneficial for skeletal muscle functions across all ages. Regimented exercise is often prescribed as an effective treatment/prophylaxis for age-related loss of muscle mass and function, known as sarcopenia, and plays an important role in the maintenance of mobility and functional independence in the elderly. However, response to exercise declines with aging, resulting in limited gain of muscle strength and endurance. These changes likely reflect age-dependent alterations in transcriptional response underlying the muscular adaptation to exercise. The exact changes in gene expression accompanying exercise, however, are largely unknown, and elucidating them is of a great clinical interest for understanding and optimizing the exercise-based therapies for sarcopenia. In order to characterize the exercise-induced transcriptomic changes in aged muscle, a paired-end RNA sequencing was performed on rRNA-depleted total RNA extracted from the gastrocnemius muscles of 24 months-old mice after 8 weeks of regimented exercise (exercise group) or no formal exercise program (sedentary group). Differential gene expression analysis of aged skeletal muscle revealed upregulations in the group of genes involved in neurotransmission and neuroexcitation, as well as equally notable absence of anabolic gene upregulations in the exercise group. In particular, genes encoding the transporters and receptor components of glutaminergic transmission were significantly upregulated in exercised muscles, as exemplified by Gria 1, Gria 2 and Grin2c encoding glutamate receptor 1, 2 and 2C respectively, Grin1 and Grin2b encoding N-methyl-d-aspartate receptors (NMDARs), Nptx1 responsible for glutaminergic receptor clustering, and Slc1a2 and Slc17a7 regulating synaptic uptake of glutamate. These changes were accompanied by an increase in the post-synaptic density of NMDARs and acetylcholine receptors (AChRs), as well as their innervation at neuromuscular junctions (NMJs). These results suggest that neural responses predominate the adaptive response of aged skeletal muscle to exercise, and indicate a possibility that glutaminergic transmission at NMJs may be present and responsible for synaptic protection and neural remodeling accompanying the exercise-induced functional enhancement in aged skeletal muscle. In addition, the absence of upregulations in the anabolic pathways highlights them as the area of potential pharmacological targeting for optimizing exercise-led sarcopenia therapy.
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http://dx.doi.org/10.1016/j.ygeno.2021.06.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403630PMC
September 2021

Incised urethral diversion reduces the rate of fistula after one-stage hypospadias repair: a single-center retrospective controlled study.

World J Urol 2021 May 26. Epub 2021 May 26.

Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33, Badachu Road, Shijingshan, Beijing, 100144, China.

Objective: Urethrocutaneous fistula is the most prevalent complication after hypospadias repair. The aim of this study was to evaluate whether incised urethral diversion was superior to traditional transurethral diversion in minimizing complications.

Patients And Methods: We retrospectively collected and analyzed 113 cases with proximal penile or penoscrotal hypospadias that were repaired by one-stage transverse preputial island flap urethroplasty between January 2016 and January 2020. Of those cases, 60 used incised urethral diversion (group A), whereas the remaining 53 were managed by transurethral diversion (group B) for urinary drainage after surgery. Postoperative complications in both groups were assessed for fistula, urethral diverticulum, meatal stenosis, wound infection, and distal urethral breakdown.

Results: Fistula was reported in 2 patients (3.3%) in group A, while it was observed in 15 patients (28.3%) in group B (p < 0.001). Wound infection occurred in one patient (1.7%) in group A, compared with six patients (11.3%) in group B (p < 0.05). The incidence rates of distal urethral breakdown were 1.7% (1/60) and 11.3% (6/53) for group A and group B, respectively (p < 0.05). One patient (1.7%) in group A and three patients (5.7%) in group B had a meatal stenosis (p > 0.05). There were two patients who developed urethral diverticulum in either group (p > 0.05).

Conclusions: The use of incised urethral diversion for urinary drainage had an advantage over transurethral diversion in one-stage hypospadias repair with respect to the post-operational fistula occurrence, wound infection, and distal urethral breakdown.
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http://dx.doi.org/10.1007/s00345-021-03732-3DOI Listing
May 2021

In Vivo Printing of Nanoenabled Scaffolds for the Treatment of Skeletal Muscle Injuries.

Adv Healthc Mater 2021 05 28;10(10):e2002152. Epub 2021 Feb 28.

Department of Mechanical and Materials Engineering, University of Nebraska, Lincoln, NE, 68588, USA.

Extremity skeletal muscle injuries result in substantial disability. Current treatments fail to recoup muscle function, but properly designed and implemented tissue engineering and regenerative medicine techniques can overcome this challenge. In this study, a nanoengineered, growth factor-eluting bioink that utilizes Laponite nanoclay for the controlled release of vascular endothelial growth factor (VEGF) and a GelMA hydrogel for a supportive and adhesive scaffold that can be crosslinked in vivo is presented. The bioink is delivered with a partially automated handheld printer for the in vivo formation of an adhesive and 3D scaffold. The effect of the controlled delivery of VEGF alone or paired with adhesive, supportive, and fibrilar architecture has not been studied in volumetric muscle loss (VML) injuries. Upon direct in vivo printing, the constructs are adherent to skeletal muscle and sustained release of VEGF. The in vivo printing of muscle ink in a murine model of VML injury promotes functional muscle recovery, reduced fibrosis, and increased anabolic response compared to untreated mice. The in vivo construction of a therapeutic-eluting 3D scaffold paves the way for the immediate treatment of a variety of soft tissue traumas.
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http://dx.doi.org/10.1002/adhm.202002152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137605PMC
May 2021

Miniaturized Needle Array-Mediated Drug Delivery Accelerates Wound Healing.

Adv Healthc Mater 2021 04 15;10(8):e2001800. Epub 2021 Feb 15.

Department of Biomedical Engineering, University of Connecticut, Farmington, CT, 06030, USA.

A major impediment preventing normal wound healing is insufficient vascularization, which causes hypoxia, poor metabolic support, and dysregulated physiological responses to injury. To combat this, the delivery of angiogenic factors, such as vascular endothelial growth factor (VEGF), has been shown to provide modest improvement in wound healing. Here, the importance of specialty delivery systems is explored in controlling wound bed drug distribution and consequently improving healing rate and quality. Two intradermal drug delivery systems, miniaturized needle arrays (MNAs) and liquid jet injectors (LJIs), are evaluated to compare effective VEGF delivery into the wound bed. The administered drug's penetration depth and distribution in tissue are significantly different between the two technologies. These systems' capability for efficient drug delivery is first confirmed in vitro and then assessed in vivo. While topical administration of VEGF shows limited effectiveness, intradermal delivery of VEGF in a diabetic murine model accelerates wound healing. To evaluate the translational feasibility of the strategy, the benefits of VEGF delivery using MNAs are assessed in a porcine model. The results demonstrate enhanced angiogenesis, reduced wound contraction, and increased regeneration. These findings show the importance of both therapeutics and delivery strategy in wound healing.
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http://dx.doi.org/10.1002/adhm.202001800DOI Listing
April 2021

The Effect of Arm Position on Breast Volume Measurement Using Three-dimensional Imaging.

Aesthetic Plast Surg 2021 Jan 25. Epub 2021 Jan 25.

Department of Aesthetic and Reconstructive Breast Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33 Ba-Da-Chu Road, Shi-Jing-Shan District, Beijing, 100144, China.

Background: Three-dimensional (3D) imaging offers an objective and quantitative way to evaluate the breast volume. In this study, we aimed to investigate whether arm position can be a factor influencing the measurement of breast volume and which arm position is more stable when using 3D breast imaging in evaluating the fat volume retention rate in autologous fat grafting for breast augmentation.

Methods: Patients undergoing breast augmentation with autologous fat grafting in our department were selected for the first part of this study. Preoperative 3D breast imaging was performed at three different arm positions: at the sides, akimbo and with hands on the head. Scans on each arm position were repeated on the first day after surgery, taking six scans in total. Breast volume change (BVC) was compared before and after surgery. The patients planning to receive bilateral mammaplasty in our department were selected for the second part of this study. Two repeated 3D scans were performed at the sides, akimbo and hands on the head, and then, the breast volume change error (BVCE) was compared.

Results: Twenty-five patients (n = 50 breasts) were included in the first part of study. For the patients who received 100-200 ml fat injection, compared with hands on the head, a statistically significant difference in the average BVC was found at the sides and akimbo (p = 0.02). For the patients receiving more than 200 ml fat injection, there was no statistically significant difference between the groups (p > 0.05). Twenty-six patients (n = 52 breasts) were enrolled in the second part. For the average BVCE, there was no significant difference between the groups (p = 0.11).

Conclusions: The arm position during 3D breast imaging, to some extent, affects the evaluation of BVC after breast augmentation using autologous fat grafting, particularly for patients receiving less fat grafting. The arm position should be kept consistent when using 3D breast imaging in evaluating the fat volume retention rate.

Level Of Evidence Iv: 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 Table of Contents or the online Instructions to Authors www.springer.com/00266.
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http://dx.doi.org/10.1007/s00266-020-02113-2DOI Listing
January 2021

Comparison of Acellular Solutions for Ex-situ Perfusion of Amputated Limbs.

Mil Med 2020 12;185(11-12):e2004-e2012

Division of Plastic Surgery, Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

Introduction: Hypothermic ex-situ machine perfusion (MP) has been shown to be a promising alternative to static cold storage (SCS) for preservation of solid organs for transplantation and vascularized composite allotransplantation. Perfusion with blood-based perfusion solutions in austere environments is problematic due to their need for appropriate storage and short shelf life, making it impractical for military and emergency use. Acellular perfusion has been shown to be effective, but the ideal perfusate solution for MP of amputated limbs is yet to be determined. The purpose of this study is to evaluate the efficacy of alternative perfusate solutions, such as dextran-enriched Phoxilium, Steen, and Phoxilium in ex-vivo hypothermic MP of amputated limbs in a porcine model.

Materials And Methods: Amputated forelimbs from Yorkshire pigs (n = 8) were preserved either in SCS (n = 2) at 4°C for 12 hours or machine-perfused at 10°C for 12 hours with oxygenated perfusion solutions (n = 6) at a constant flow rate. The perfusates used include modified Steen-solution, Phoxilium (PHOX), or Phoxilium enriched with dextran-40 (PHODEX). The perfusate was exchanged after 1 and 6 hours of perfusion. Machine data were recorded continuously. Perfusate samples for clinical chemistry, blood gas analysis, and muscle biopsies were procured at specific timepoints and subsequently analyzed. In this semi in-vivo study, limb replantation has not been performed.

Results: After amputation, every limb was successfully transferred and connected to our perfusion device. The mean total ischemia time was 77.5 ± 5.24 minutes. The temperature of the perfusion solution was maintained at 10.18 ± 2.01°C, and perfusion pressure at 24.48 ± 10.72 mmHg. Limb weight increased by 3% in the SCS group, 36% in the PHODEX group, 25% in the Steen group, and 58% in the PHOX group after 12 hours. This increase was significant in the PHOX group compared with the SCS group. All perfusion groups showed a pressure increase of 10.99 mmHg over time due to edema. The levels of HIF-1a decreased over time in all groups except the Steen and the PHODEX group. The biomarkers of muscle injury in the perfusate samples, such as creatine kinase and lactate-dehydrogenase, showed a significant difference between groups, with highest values in the PHODEX group. No significant differences were found in the results of the blood gas analysis.

Conclusion: With the exception of significantly higher levels of creatine kinase and lactate dehydrogenase, MP with dextran-enriched Phoxilium provides similar results as that of the commercially available perfusates such as Steen, without the need for cold storage, and at circa 5% of the cost of the Steen solution. Further large-scale replantation studies are necessary to evaluate the efficacy of dextran-enriched Phoxilium as an alternate perfusate solution.
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http://dx.doi.org/10.1093/milmed/usaa160DOI Listing
December 2020

Novel application of autologous micrografts in a collagen-glycosaminoglycan scaffold for diabetic wound healing.

Biomed Mater 2020 Oct 22. Epub 2020 Oct 22.

Brigham and Women's Hospital, Boston, UNITED STATES.

Background: Therapeutic strategies that successfully combine two techniques-autologous micrografting and biodegradable scaffolds-offer great potential for improved wound repair and decreased scarring. In this study we evaluate the efficacy of a novel modification of a collagen-glycosaminoglycan scaffold with autologous micrografts using a murine dorsal wound model.

Methods: db/db mice underwent dorsal wound excision and were treated with a collagen-glycosaminoglycan scaffold (CGS), a modified collagen-glycosaminoglycan scaffold (CGS+MG) or simple occlusive dressing (Blank). The modified scaffold was created by harvesting full thickness micrografts and transplanting these into the collagen-glycosaminoglycan membrane. Parameters of wound healing, including cellular proliferation, collagen deposition, keratinocyte migration, and angiogenesis were assessed.

Results: The group treated with the micrograft-modified scaffold healed at a faster rate, showed greater cellular proliferation, collagen deposition, and keratinocyte migration with higher density and greater maturity of microvessels. The grafts remained viable within the scaffold with no evidence of rejection. Keratinocytes were shown to migrate from the wound border and from the micrograft edges towards the center of the wound, while cellular proliferation was present both at the wound border and wound bed.

Conclusion: We report successful treatment of diabetic wounds with a novel collagen-glycosaminoglycan scaffold modified with full-thickness automicrografts. Differences in cellular migration and proliferation offer maiden evidence on the mechanisms of wound healing. Clinically, the successful scaffold engraftment, micrograft viability and improved wound healing offer promising results for the development of a new therapeutic modality for wound repair.
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http://dx.doi.org/10.1088/1748-605X/abc3dcDOI Listing
October 2020

Loss of ARNT in skeletal muscle limits muscle regeneration in aging.

FASEB J 2020 12 8;34(12):16086-16104. Epub 2020 Oct 8.

Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23-25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2-3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle-specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT-deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle.
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http://dx.doi.org/10.1096/fj.202000761RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756517PMC
December 2020

Low mortality oxidative stress murine chronic wound model.

BMJ Open Diabetes Res Care 2020 09;8(1)

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Introduction: Investigators have struggled to produce a reliable chronic wound model. Recent progress with antioxidant enzyme inhibitors shows promise, but mortality rates are high. We modified the dosage and administration of an antioxidant enzyme inhibitor regimen to reduce mortality while inducing a chronic wound environment.

Research Design And Methods: To chemically induce a chronic wound environment, we applied modified doses of catalase (3-amino-1,2,4-triazole; intraperitoneal 0.5 g/kg) and glutathione peroxidase (mercaptosuccinic acid; topical 300 mg/kg) inhibitors to the dorsal wounds of 11-week-old db/db mice. A cohort of these mice was treated with a collagen-glycosaminoglycan scaffold. Both groups were compared with Diabetic control mice.

Results: This study successfully induced a chronic wound in 11-week-old db/db mice, with no animal deaths. The antioxidant enzyme treated groups showed delayed wound contraction and significantly higher levels of inflammatory tissue, collagen deposition, cellular proliferation and leukocyte infiltration than the Diabetic control group. Angiogenesis was significantly higher in the antioxidant enzyme treated groups, but the vessels were immature and friable. Scaffold engraftment was poor but appeared to promote blood vessel maturation.

Conclusions: Overall, the two in vivo groups treated with the antioxidant enzyme inhibitors appeared to be arrested in the inflammatory stage of wound healing, while the Diabetic control group progressed to the maturation phase and ultimately remodeling. This model may be instrumental for the development of new wound therapeutics.
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http://dx.doi.org/10.1136/bmjdrc-2020-001221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478002PMC
September 2020

Masks are musts: Airborne transmission makes face covering indispensable.

Authors:
Yori Endo

Br J Surg 2020 10 31;107(11):e534-e535. Epub 2020 Aug 31.

Harvard Medical School, Brigham and Women's Hospital, Boston, MA.

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http://dx.doi.org/10.1002/bjs.12010DOI Listing
October 2020

Adherence to Personal Protective Equipment Guidelines During the COVID-19 Pandemic: A Worldwide Survey Study.

Br J Surg 2020 Oct 24;107(11):e526-e528. Epub 2020 Aug 24.

Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.

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http://dx.doi.org/10.1002/bjs.12001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460957PMC
October 2020

Optimizing Skeletal Muscle Anabolic Response to Resistance Training in Aging.

Front Physiol 2020 23;11:874. Epub 2020 Jul 23.

Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Loss of muscle mass and strength with aging, also termed sarcopenia, results in a loss of mobility and independence. Exercise, particularly resistance training, has proven to be beneficial in counteracting the aging-associated loss of skeletal muscle mass and function. However, the anabolic response to exercise in old age is not as robust, with blunted improvements in muscle size, strength, and function in comparison to younger individuals. This review provides an overview of several physiological changes which may contribute to age-related loss of muscle mass and decreased anabolism in response to resistance training in the elderly. Additionally, the following supplemental therapies with potential to synergize with resistance training to increase muscle mass are discussed: nutrition, creatine, anti-inflammatory drugs, testosterone, and growth hormone (GH). Although these interventions hold some promise, further research is necessary to optimize the response to exercise in elderly patients.
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http://dx.doi.org/10.3389/fphys.2020.00874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390896PMC
July 2020

Identification of key microRNAs and target genes for the diagnosis of bone nonunion.

Mol Med Rep 2020 Apr 21;21(4):1921-1933. Epub 2020 Feb 21.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

A number of recent studies have highlighted the causes of bone nonunion (BN), however, the rate of BN incidence continues to rise and available therapeutic options to treat this condition remain limited. Thus, to prevent disease progression and improve patient prognosis, it is vital that BN, or the risk thereof, be accurately identified in a timely manner. In the present study, bioinformatics analyses were used to screen for the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between patients with BN and those with bone union, using data from the Gene Expression Omnibus database. Furthermore, clinical samples were collected and analyzed by reverse transcription‑quantitative PCR and western blotting. In vitro and in vivo experiments were carried out to confirm the relationship between BN and the DEGs of interest, in addition to being used to explore the underlying molecular mechanism of BN. Functional enrichment analysis of the downregulated DEGs revealed them to be enriched for genes associated with 'ECM‑receptor interactions', 'focal adhesion', 'and the calcium signaling pathway'. When comparing DEM target genes with these DEGs, nine DEGs were identified as putative DEM targets, where hsa‑microRNA (miR)‑1225‑5p‑CCNL2, hsa‑miR‑339‑5p‑PRCP, and hsa‑miR‑193a‑3p‑mitogen‑activated protein kinase 10 (MAPK10) were the only three pairs which were associated with decreased gene expression levels. Furthermore, hsa‑miR‑193a‑3p was demonstrated to induce BN by targeting MAPK10. Collectively, the results of the present study suggest that hsa‑miR‑193a‑3p may be a viable biomarker of BN.
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http://dx.doi.org/10.3892/mmr.2020.10996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057810PMC
April 2020

Use of venous couplers in microsurgical lower extremity reconstruction: A systematic review and meta-analysis.

Microsurgery 2021 Jan 30;41(1):50-60. Epub 2020 Mar 30.

Department of Hand-, Plastic and Reconstructive Surgery, Microsurgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.

Background: Free tissue transfer for lower limb reconstruction has become a workhorse procedure for limb-salvage. Compared with other recipient sites, the lower extremity has a higher risk of microvascular complications, in particular with venous anastomosis. The study's objective is to evaluate the evidence, safety, and efficacy of venous coupler use in microsurgical anastomosis in lower limb reconstruction to provide objective appraisal of the surgical techniques.

Methods: A systematic review (SR) and meta-analysis (MA) were performed analyzing articles from PubMed, Cochrane, Embase, and Web of Science from January 1990, to August 2018. Abstracts and titles were screened and assessed for eligibility by independent reviewers. Following full-text review, articles were included in the SR and MA. Case reports were excluded. Cochrane Collaboration and the Quality of Reporting of Meta-analyses (QUOROM) guidelines were followed.

Results: Out of 15 included studies that met the inclusion criteria for the SR, 9 were included in MA. Patients treated with venous couplers did not experience more surgical complications (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.48-1.33; p = .38), total failure (RR 0.61; 95% CI 0.22-1.70; p = .34), venous compromise (RR 0.72; 95% CI 0.23-2.27; p = .57), arterial compromise (RR 0.85; 95% CI 0.25-2.88; p = .80), partial failure (RR 0.77; 95% CI 0.33-1.77; p = .54), or reoperation (RR 11.79; 95% CI 0.49-286.55; p = .13) in comparison with hand-sewn anastomosis.

Conclusions: Outcomes of venous couplers in lower limb reconstruction are comparable to those of hand-sewn anastomosis. However, this study was limited by the quality of the available literature. Additional prospective studies should aim to directly compare both techniques and potential further benefits in clinical trials.
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http://dx.doi.org/10.1002/micr.30581DOI Listing
January 2021

The lncRNA Rhno1/miR-6979-5p/BMP2 Axis Modulates Osteoblast Differentiation.

Int J Biol Sci 2020 12;16(9):1604-1615. Epub 2020 Mar 12.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

The roles of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) as regulators of mRNA expression in various diseases have recently been reported. Osteoblast differentiation is the vital process which mediates bone formation and fracture healing. In present study, we found microRNA-6979-5p (miR-6979-5p) to be the most differentially expressed miRNA between normal bone and calluses of mice, and overexpression of miR-6979-5p was negatively associated with osteoblast differentiation. Through luciferase assays, we found evidence that bone morphogenetic protein 2 (BMP2) is a miR-6979-5p target gene that positively regulates osteoblast differentiation. We further identified the lncRNA Rhno1 as a competing endogenous RNA (ceRNA) of miR-6979-5p, and we verified that it was able to influence osteoblast differentiation both and . In summary, our data indicates that the lncRNA Rhno1/miR-6979-5p/BMP2 axis is a significant regulatory mechanism controlling osteoblast differentiation, and it may thus offer a novel therapeutic strategy for fracture healing.
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http://dx.doi.org/10.7150/ijbs.38930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097916PMC
August 2021

Hypothermic Ex Situ Perfusion of Human Limbs With Acellular Solution for 24 Hours.

Transplantation 2020 09;104(9):e260-e270

Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Background: Machine perfusion (MP) has evolved as a promising approach for the ex situ preservation in organ transplantation. However, the literature on the use of MP in human vascularized composite allografts is scarce. The aim of this study was to evaluate the effects of hypothermic MP with an acellular perfusate in human upper extremities and compare with the current gold standard of static cold storage (SCS).

Methods: Six upper extremities were assigned to either MP (n = 3) or SCS (n = 3) conditions for 24 h. MP-extremities were perfused with oxygenated Steen solution at a constant pressure of 30 mm Hg and 10°C.

Results: Median total ischemia time was 213 min (range, 127-222 min). Myoglobin, creatine-kinase (CK) showed increased levels at the start of MP (medians: myoglobin: 4377 ng/mL, CK: 1442 U/L), peaking 6 h after perfusate exchange (medians: myoglobin: 9206 ng/mL, CK: 3995 U/L) at timepoint 24. Lactate levels decreased from a median of 6.9-2.8 mmol/L over time. Expression of hypoxia-inducible factor 1-alpha peaked in the SCS-group after 8 h, followed by a decrease. Increased hypoxia-inducible factor 1-alpha expression in the MP group was delayed until 20 h. Perfusion pressure, temperature, and circuit flow were maintained at median of 30.88 mm Hg, 9.77°C, and 31.13 mL/min, respectively. Weight increased 1.4% in the SCS group and 4.3% in the MP group over 24 h.

Conclusions: Hypothermic ex situ perfusion with an oxygenated acellular Steen solution may extend the allowable extracorporeal preservation time by a factor of 4-6 compared to SCS and holds promise to be beneficial for vascularized composite allograft recipients and victims of traumatic major limb amputation.
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http://dx.doi.org/10.1097/TP.0000000000003221DOI Listing
September 2020

LncRNA KCNQ1OT1 accelerates fracture healing via modulating miR-701-3p/FGFR3 axis.

FASEB J 2020 04 14;34(4):5208-5222. Epub 2020 Feb 14.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Emerging evidence highlights the role of the long noncoding RNA (lncRNA) KCNQ1OT1 in fracture healing. Osteoblast proliferation, migration, and survival are pivotal during this process. In this study, we aimed to improve our understanding of the regulatory role of lncRNA KCNQ1OT1 during osteoblast proliferation, migration, and survival. We searched the gene expression omnibus databases and LncBase Experimental V.2 to identify key microRNAs (miRNAs) targets of KCNQ1OT1. MiR-701-3p was selected as a differentially expressed miRNA and RNA immunoprecipitation assays were performed to verify its interaction with KCNQ1OT1. Fibroblast growth factor receptor 3 (FGFR3) was also identified as a target of miR-701-3p. We further identified KCNQ1OT1 as a competing endogenous RNA of miR-701-3p that could influence osteoblast proliferation, migration, and apoptosis in vitro and in vivo. Taken together, our results indicate that the KCNQ1OT1/miR-701-3p/FGFR3 axis is an important regulator of osteoblast proliferation, migration, and apoptosis, and provide a new therapeutic avenue for fracture healing.
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http://dx.doi.org/10.1096/fj.201901864RRDOI Listing
April 2020

Circulating Exosomal miR-20b-5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes-Associated Impaired Wound Healing.

Small 2020 01 23;16(3):e1904044. Epub 2019 Dec 23.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P. R. China.

At present, developing therapeutic strategies to improve wound healing in individuals with diabetes remains challenging. Exosomes represent a promising nanomaterial from which microRNAs (miRNAs) can be isolated. These miRNAs have the potential to exert therapeutic effects, and thus, determining the potential therapeutic contributions of specific miRNAs circulating in exosomes is of great importance. In the present study, circulating exosomal miRNAs are identified in diabetic patients and assessed for their roles in the context of diabetic wound healing. A significant upregulation of miR-20b-5p is observed in exosomes isolated from patients with type 2 diabetes mellitus (T2DM), and this miRNA is able to suppress human umbilical vein endothelial cell angiogenesis via regulation of Wnt9b/β-catenin signaling. It is found that the application of either miR-20b-5p or diabetic exosomes to wound sites is sufficient to slow wound healing and angiogenesis. In diabetic mice, it is found that knocking out miR-20b-5p significantly enhances wound healing and promotes wound angiogenesis. Together, these findings thus provide strong evidence that miR-20b-5p is highly enriched in exosomes from patients with T2DM and can be transferred to cells of the vascular endothelium, where it targets Wnt9b signaling to negatively regulate cell functionality and angiogenesis.
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http://dx.doi.org/10.1002/smll.201904044DOI Listing
January 2020

CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis.

Aging (Albany NY) 2019 12 17;11(24):11988-12001. Epub 2019 Dec 17.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Fracture healing is a complex process involving various cell types, cytokines, and mRNAs. Here, we report the roles of the circRNA AFF4/miR-7223-5p/PIK3R1 axis during fracture healing. We found that increased expression of PIK3R1 during fracture healing is directly associated with augmented proliferation and decreased apoptosis of MC3T3-E1 cells. Furthermore, miR-7223-5p targeted PI3KR1 and inhibited MC3T3-E1 proliferation while promoting apoptosis. CircRNA AFF4 acted as a sponge of miR-7223-5p, thereby promoting MC3T3-E1 cell proliferation and inhibiting apoptosis. Local injection of circRNA AFF4 into femoral fracture sites promoted fracture healing while the injection of miR-7223-5p delayed healing. These findings suggest that CircRNA AFF4 promotes fracture healing by targeting the miR-7223-5p/PIK3R1 axis, and suggests miR-7223-5p, CircRNA AFF4, and the miR-7223-5p/PIK3R1 axis are potential therapeutic targets for improving fracture healing.
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http://dx.doi.org/10.18632/aging.102524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949079PMC
December 2019

IL-10 induces MC3T3-E1 cells differentiation towards osteoblastic fate in murine model.

J Cell Mol Med 2020 01 21;24(1):1076-1086. Epub 2019 Nov 21.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Interleukin-10 (IL-10) displays well-documented anti-inflammatory effects, but its effects on osteoblast differentiation have not been investigated. In this study, we found IL-10 negatively regulates microRNA-7025-5p (miR-7025-5p), the down-regulation of which enhances osteoblast differentiation. Furthermore, through luciferase reporter assays, we found evidence that insulin-like growth factor 1 receptor (IGF1R) is a miR-7025-5p target gene that positively regulates osteoblast differentiation. In vivo studies indicated that the pre-injection of IL-10 leads to increased bone formation, while agomiR-7025-5p injection delays fracture healing. Taken together, these results indicate that IL-10 induces osteoblast differentiation via regulation of the miR-7025-5p/IGF1R axis. IL-10 therefore represents a promising therapeutic strategy to promote fracture healing.
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http://dx.doi.org/10.1111/jcmm.14832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933380PMC
January 2020

A porous collagen-GAG scaffold promotes muscle regeneration following volumetric muscle loss injury.

Wound Repair Regen 2020 01 7;28(1):61-74. Epub 2019 Nov 7.

Division of Plastic Surgery, Brigham and Women's Hospital, Boston, Massachusetts.

Volumetric muscle loss (VML) is a segmental loss of skeletal muscle which commonly heals with fibrosis, minimal muscle regeneration, and loss of muscle strength. Treatment options for these wounds which promote functional recovery are currently lacking. This study was designed to investigate whether the collagen-GAG scaffold (CGS) promotes functional muscle recovery following VML. A total of 66 C57/Bl6 mice were used in a three-stage experiment. First, 24 animals were split into three groups which underwent sham injury or unilateral quadriceps VML injury with or without CGS implantation. Two weeks post-surgery, muscle was harvested for histological and gene expression analysis. In the second stage, 18 mice underwent bilateral quadriceps VML injury, followed by weekly functional testing using a treadmill. In the third stage, 24 mice underwent sham or bilateral quadriceps VML injury with or without CGS implantation, with tissue harvested six weeks post-surgery for histological and gene expression analysis. VML mice treated with CGS demonstrated increased remnant fiber hypertrophy versus both the VML with no CGS and uninjured groups. Both VML groups showed greater muscle fiber hypertrophy than non-injured muscle. This phenomenon was still evident in the longer-term experiment. The gene array indicated that the CGS promoted upregulation of factors involved in promoting wound healing and regeneration. In terms of functional improvement, the VML mice treated with CGS ran at higher maximum speeds than VML without CGS. A CGS was shown to enhance muscle hypertrophy in response to VML injury with a resultant improvement in functional performance. A gene array highlighted increased gene expression of multiple growth factors following CGS implantation. This suggests that implantation of a CGS could be a promising treatment for VML wounds.
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http://dx.doi.org/10.1111/wrr.12768DOI Listing
January 2020

Quaternized chitosan-Matrigel-polyacrylamide hydrogels as wound dressing for wound repair and regeneration.

Carbohydr Polym 2019 Dec 8;226:115302. Epub 2019 Sep 8.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Hydrogels could be promising wound healing dressings that maintain a moist environment in the wound site and accelerate wound healing. However, the lack of antibacterial effect, suitable mechanical property and adhesiveness limits their applications. Here, we designed a quaternized chitosan-Matrigel-polyacrylamide (QCS-M-PAM) hydrogel with multi-functions. The morphology, swelling ratio, mechanical test, antimicrobial property, hemostatic performance and biocompatibility of the hybrid hydrogel were investigated in vitro and vivo. The hybrid hydrogel showed a three-dimensional (3D) microporous structure, high swelling ratio, excellent stretchable and compressive property, similar modulus to human skin, good adhesiveness, and low cytotoxicity. The results of histology and molecular testing in vivo demonstrated that the hybrid hydrogel could significantly enhance wound healing, collagen deposition, and induce skin adnexal regeneration by upregulating anti-inflammatory factors, and downregulating proinflammatory factors. Together, the present antibacterial hydrogels with hemostatic and adhesive properties are considered to have promising potential used as wound dressings for full-thickness skin defect.
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http://dx.doi.org/10.1016/j.carbpol.2019.115302DOI Listing
December 2019

A comparative study of the efficacy of ultrasonics and extracorporeal shock wave in the treatment of tennis elbow: a meta-analysis of randomized controlled trials.

J Orthop Surg Res 2019 Aug 6;14(1):248. Epub 2019 Aug 6.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Rd. 1277#, Wuhan, 430022, Hubei, China.

Background: Tennis elbow or lateral epicondylitis is a common source of pain among craftsmen. Although it cannot be completely resolved, extracorporeal shock wave therapy (ESWT) and ultrasonics (US) have been found to be effective for tennis elbow as highlighted in previously published randomized controlled trials (RCTs) and reviews. However, the efficacy of these two therapies in treating tennis elbow is unknown. This meta-analysis compares the effectiveness of ESWT and US in relieving pain and restoring the functions of tennis elbow following tendinopathy.

Methods: RCTs published in the PubMed, Embase, Cochrane Library, and SpringerLink databases comparing ESWT and US in treating tennis elbow were identified by a software and manual search. The risk of bias and clinical relevance of the included studies were assessed. Publication bias was explored using funnel plot and statistical tests (Egger's test and Begg's test). The major outcomes of the studies were analyzed using the Review Manager 5.3.

Results: Five RCTs comprising five patients were included in the present meta-analysis. The results revealed a significantly lower VAS score of pain in the ESWT group (1 month: MD = 4.47, p = 0.0001; 3 months: MD = 20.32, p < 0.00001; and 6 months: MD = 4.32, p < 0.0001) compared to US. Besides, the grip strength was markedly higher 3 months after the intervention in ESWT (MD = 8.87, p < 0.00001) than in the US group. Although no significant difference was observed in the scores of the elbow function after 3 months of treatment (SMD = 1.51, p = 0.13), the subjective scores of elbow functions were found to be better in the ESWT group (SMD = 3.34; p = 0.0008) compared to the US group.

Conclusions: Although there was no significant difference in the elbow function evaluation scores between ESWT and US, the superiority of the ESWT group in the VAS of pain (both at 1 month, 3 months, and 6 months follow-ups) raised grip strength in ESWT group and the scores for subjective evaluation of efficacy indicated that ESWT offers more effective therapy for lateral epicondylitis than US therapy.
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http://dx.doi.org/10.1186/s13018-019-1290-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683364PMC
August 2019
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