The Concept of Oncoplastic Breast Surgery Applied in Surgery for a Giant Fibroadenoma

The treatment of a 40-year-old woman with a giant fibroadenoma in her left breast is presented. The fibroadenoma measured 14 × 5 × 3 cm and weighed 170 g. We demonstrate that the surgical strategy and the reconstructive techniques in oncoplastic breast cancer surgery successfully can be applied to the treatment of these rare benign tumours improving the cosmetic and functional outcome.

Inferior Pedicle Breast Reduction for the Management of Gestational Gigantomastia: Literature Review and a Case Presentation

Background: The actual cause of Gestational gigantomastia (Gg) remains a dilemma. Its treatment has ideally been surgical, employing most commonly the different pedicle techniques in the last decade. Aim: This paper reviews the literature on the management of Gg using the inferior pedicle technique (IPT) and supports it with a successful case presentation using the IPT. Method: Using the PubMed search engine and Google scholar, literature search was done for Gg treated with the inferior pedicle reduction method. Published literature from other sources was also included. Data obtained was cleaned and analysed. The inferior pedicle breast reduction technique was employed without any modification in the normal procedure for the case presented. Results: Thirty-one literature addressing Gg and IPT were identified. Most surgeons use this technique with very good outcomes. Our patient confirmed reduced breast mould, firm and adolescent looking breast with no back, shoulder, neck and rib pains. She also experienced with time increased nipple areolar sensation, ability to undertake all tasks with ease and a new sense of confidence. Conclusion: The inferior pedicle breast reduction technique can be the standard treatment for gestational gigantomastia with the length from suprasternal notch to the nipple ≤ 50 cm that present without any anatomical complications.

全颅骨切开成形矫正早期矢状缝早闭头颅畸形

目的:探讨矢状缝早闭舟状头畸形的早期手术治疗方法。方法:患儿采取改良的俯卧位,通过头皮冠状切口显露从眉间至枕骨大孔后唇的整个颅盖,切开颅骨分离双侧额骨和双侧顶-枕部骨块。对额骨和枕骨进行放射状切开、塑形纠正前后部隆突畸形;切除部分额、顶骨块缩短头颅前后径;在颞、顶骨下部采用"木桶板"样截骨以及放射状切开、塑形两侧顶骨纠正头颅狭窄畸形。结果:手术后4例舟状头畸形明显改善,外形良好,无严重并发症。术后随访3～10月,头颅外形维持良好,畸形无复发。结论:包括双侧额、顶、枕、颞全颅骨切开重新塑形的手术方法能够有效地矫正婴幼儿矢状缝早闭舟状头畸形。

手外伤急诊游离腹直肌皮瓣移植术

肢体软组织创伤缺损若能在损伤头几天尽早得到覆盖闭合,通常能极好地预防慢性感染及软组织的进一步坏死。因抢救生命而必须截肢除外,急诊使用游离皮瓣的指征历来争论不清,特别是修复后的血管、神经、肌腱及骨骼等裸露于创面时。

The technique of utilizing a single gracilis functional muscle transfer to restore quadriceps function following sarcoma surgery

Aim:Quadriceps strength and knee extension,the most important factors limiting the ability to rise from a chair,are crucial for walking at an appropriate speed,ascending and descending stairs,and performing activities such as running,dancing,and jumping.Resection of the anterior compartment of the thigh,including all four quadriceps muscles,for the treatment of a sarcoma is uncommon;however,when necessary,it is very debilitating and adversely affects a patient's quality of life without functional reconstruction.Currently,there are a limited number of complex and difficult reconstructions to restore quadriceps function that have been described with variable outcomes.We describe a simple technique that employs a single gracilis functional muscle transfer to replace essential quadriceps function.Methods:This is a case series describing the use of either a free or pedicled single gracilis muscle to restore quadriceps function following sarcoma resection.Results:Four patients underwent an anterior compartment sarcoma resection that resulted in a large segmental defect and/or denervation of all four quadriceps muscles such that no quadriceps function would remain without reconstruction.All four patients underwent a functional reconstruction using a single gracilis.Three of the living patients achieved British Medical Research Counsel Grade 4 strength,can achieve full knee extension,are able to navigate stairs,and are able to ambulate without a brace.The fourth patient unfortunately was deceased in under three months following his tumor resection.Conclusion:Despite its small size in comparison to the quadriceps muscles,with physiotherapy and training,the gracilis muscle demonstrates the capacity to hypertrophy and replace quadriceps function following limb salvage surgery.

运用闭孔岛状股部皮瓣行直肠阴道放射性瘘修复

Background. Rectovaginal fistulae are a known complication of pelvic ra diother apy utilizing locally applied isotope implants. Most often, either permanent col ostomy or reconstruction with a well-vascularized flap is necessary. Traditiona l techniques for fistula repair utilize bulky muscle flaps, disfiguring pudendal artery flaps or may require laparotomy. Case. We describe the management of a 2 6-year-oldwoman with a large radiation induced rectovaginal fistula. A fascioc utaneous medial thigh flap based on terminal branches of the obturator artery an d vein was used without colostomy and resulted in pain-free sexual function and minimal vulva disfigurement. Conclusion. A medial thigh fasciocutaneous flap wi thout muscle can be transferred into the vagina on the obturator vessels and may become the preferred method for managing large rectovaginal fistulas.

Engineered nucleus-free mesenchymal stem cells (MSCs) for the targeted delivery of therapeutics to disease site

Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MSCs) for targeted delivery of therapeutics to disease site.1 MSCs have emerged as promising vehicles of therapeutic delivery.2,3 MSCs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MSCs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.

Corrigendum to “Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference” [Genes & Diseases 5(2018):172–184]

The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"group.In Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"group.In Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.

Bone Morphogenic Protein 9(BMP9)/Growth Differentiation Factor 2(GDF2)modulates mouse adult hippocampal neurogenesis by regulating the survival of early neural progenitors

Adult neurogenesis occurs in two specialized regions of the mammalian brain,the subventricular zone(SVZ)and the subgranular zone(SGZ)of the dentate gyrus(DG).^(1)Adult hippocampal neural stem cells(NSCs),referred to as Type 1 cells represented by radial glia-like cells(RGLs),generate Type 2 cells that are divided into Type 2a and Type 2 b subpopulations,the latter of which give rise to Type 3 cells(neuroblasts).

Corrigendum to “The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs” [Genes & Diseases 5 (2018) 62–74]

The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19"group.We confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and unchanged.The authors would like to apologize for any inconvenience caused.

A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)

Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult tissues.At least 14 BMPs have been identified in mammals.Different BMPs exert distinct but overlapping biological functions.Through a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs.Nonetheless,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated.Here,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs.Hierarchical clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 cluster.We also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase pathway.Furthermore,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR pathways.While the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs.

Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference

Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.

Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside

With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.

The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs

While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders.

The neck burn scar contracture:a concept of effective treatment

A neck scar contracture can severely and negatively affect the function of mastication, phonic, or breathing and result in neck pain and issues with esthetics. The best way is of course to avoid such contracture by means of non-surgical treatment such as use of a growth factor. The basic fibroblastic growth factor is clinically well proven in decreasing scar formation and improving healing. There are numerous reconstructive methods for neck contracture, especially when the lesions are relatively limited in part of the neck. However, a very severe and full circumferential scar contracture requires extensive reconstruction. The thin groin flap is one of the answers and well matches with the tissue texture and maintains the flexibility. Even with extensive burns and delayed reconstructions due to resuscitation first, the groin area is well preserved and can be safely harvested by dual vasculature systems of the superficial circumflex iliac artery and superficial epigastric artery, which warrant more reliability compared to the perforator flaps in this area. More demanding and stringent forms of the neck burn scar contracture are the sequelae of radiation. A radiation burn or radiation injury can be progressing and hard to heal. Adipose-derived stem cells can reverse the scar contracture as the surrounding tissue is softened and can accelerate wound healing. In this review, different types of neck burn scar contracture and reconstructive methods are summarized, including innovative use of bFGF and ADSCs in the management of difficult wound healing and scar contracture.

The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be determined.Heterotopicossification(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues.Hypoxia andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote HO.However,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to beelucidated.Here,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell fate.Usingsingle-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in MPCs.Zeugopod mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in vivo.ScRNA-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of HO.Importantly,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1αdeletion.From a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic metabolism.This suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC fate.These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

Fat injection to correct contour deformities of the reconstructed breast:a single surgeon experience

Aim:Autologous fat grafting has gained acceptance as a technique to improve aesthetic outcomes in breast reconstruction.The purpose of this study was to share our clinical experience using autologous fat injection to correct contour deformities during breast reconstruction.Methods:A single surgeon,prospectively maintained database of patients who underwent autologous fat injection during breast reconstruction from January 2008 to November 2013 at McGill University Health Center was reviewed.Patient characteristics,breast history,type of breast reconstruction,volume of fat injected,and complications were analyzed.Results:One hundred and twenty-four patients benefited from autologous fat injection from January 2008 to November 2013,for a total of 187 treated breasts.The patients were on average 49.3 years old(±8.9 years).Fat was harvested from the medial thighs(20.5%),flanks(39.1%),medial thighs and flanks(2.9%),trochanters(13.3%),medial knees(2.7%),and abdomen(21.9%).An average of 49.25 mL of fat was injected into each reconstructed breast.A total of 187 breasts in 124 patients were lipo-infiltrated during the second stage of breast reconstruction.Thirteen breasts(in 12 separate patients)were injected several years after having undergone lumpectomy and radiotherapy.Of the 187 treated breasts,118 were reconstructed with expanders to implants,45 with deep inferior epigastric perforator flaps,9 with latissimus dorsi flaps with implants,4 with transverse rectus abdominis myocutaneous flaps,and 13 had previously undergone lumpectomy and radiotherapy.Six complications were noted in the entire series,for a rate of 3.2%.All were in previously radiated breasts.Average follow-up time was 12 months(range:2-36 months).Conclusion:Fat injection continues to grow in popularity as an adjunct to breast reconstruction.Our experience demonstrates a low complication rate as compared to most surgical interventions of the breast and further supports its safety in breast reconstruction.However,caution should be used when treating previously radiated breasts.

Long noncoding RNA(lncRNA)H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases

Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

Niclosamide(NA)overcomes cisplatin resistance in human ovarian cancer

Ovarian cancer(OC)is one of the most lethal malignancies of the female reproduc-tive system.OC patients are usually diagnosed at advanced stages due to the lack of early diag-nosis.The standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy,while several targeted therapies have recently been approved for maintenance treatment.The vast majority of OC patients relapse with chemoresistant tu-mors after an initial response.Thus,there is an unmet clinical need to develop new therapeu-tic agents to overcome the chemoresistance of OC.The anti-parasite agent niclosamide(NA)has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including OC.Here,we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant(CR)in human OC cells.To this end,we first established two CR lines SKOV3CR and OVCAR8CR that exhibit the essential biological characteristics of cisplatin resistance in human cancer.We showed that NA inhibited cell proliferation,sup-pressed cell migration,and induced cell apoptosis in both CR lines at a low micromole range.Mechanistically,NA inhibited multiple cancer-related pathways including AP1,ELK/SRF,HIF1,and TCF/LEF,in SKOV3CR and OVCAR8CR cells.NA was further shown to effectively inhibit xenograft tumor growth of SKOV3CR cells.Collectively,our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant hu-man OC,and further clinical trials are highly warranted.