Emodin activates autophagy to suppress oxidative stress and pyroptosis via mTOR-ULK1 signaling pathway and promotes multi-territory perforator flap survival.

BACKGROUND: Multi-territory perforator flap reconstruction has been proven effective in treating large skin and soft tissue defects in clinical settings. However, in view of that the multi-territory perforator flap is prone to partial postoperative necrosis, increasing its survival is the key to the success of reconstruction. In this study, we aimed to clarify the effect of emodin on multi-territory perforator flap survival. METHODS: Flap survival was assessed by viability area analysis, infrared laser imaging detector, HE staining, immunohistochemistry, and angiography. Western blotting, immunofluorescence assays, and real-time fluorescent quantitative PCR were performed to detect the indicators of oxidative stress, pyroptosis and autophagy. RESULTS: After emodin treatment, the multi-territory perforator flap showed a significantly increased survival rate, which was shown to be closely related to the inhibition of oxidative stress and pyroptosis and enhanced autophagy. Meanwhile, the use of autophagy inhibitor 3 MA was found to reverse the inhibitory effects of emodin on oxidative stress and pyroptosis and weaken the improving effect of emodin on flap survival, suggesting that autophagy plays a critical role in emodin-treated flaps. Interestingly, our mechanistic investigations revealed that the positive effect of emodin on multi-territory perforator flap was attributed to the mTOR-ULK1 signaling pathway activation. CONCLUSIONS: Emodin can inhibit oxidative stress and pyroptosis by activating autophagy via the mTOR-ULK1 pathway, thereby improving the multi-territory perforator flap survival.

M2 macrophage-derived exosomes induce angiogenesis and increase skin flap survival through HIF1AN/HIF-1α/VEGFA control.

BACKGROUND: Skin flap transplantation is a routine strategy in plastic and reconstructive surgery for skin-soft tissue defects. Recent research has shown that M2 macrophages have the potential for pro-angiogenesis during tissue healing. METHODS: In our research, we extracted the exosomes from M2 macrophages(M2-exo) and applied the exosomes in the model of skin flap transplantation. The flap survival area was measured, and the choke vessels were assessed by morphological observation. Hematoxylin and eosin (H&E) staining and Immunohistochemistry were applied to assess the neovascularization. The effect of M2-exo on the function of Human umbilical vein endothelial cells (HUVECs) was also investigated. We also administrated 2-methoxyestradiol (2-ME2, an inhibitor of HIF-1α) to explore the underlying mechanism. We tested the effects of M2-Exo on the proliferation of HUVECs through CCK8 assay and EdU staining assay. RESULTS: The survival area and number of micro-vessels in the skin flaps were increased in the M2-exo group. Besides, the dilation rate of choke vessels was also enhanced in the M2-exo group. Additionally, compared with the control group, M2-exo could accelerate the proliferation, migration and tube formation of HUVECs in vitro. Furthermore, the expression of the pro-angiogenesis factors, HIF-1α and VEGFA, were overexpressed with the treatment of the M2-exo. The expression of HIF1AN protein level was decreased in the M2-exo group. Finally, treatment with HIF-1α inhibitor reverses the pro-survival effect of M2-exo on skin flaps by interfering with the HIF1AN/HIF-1α/VEGFA signaling pathway. CONCLUSION: This study showed that M2-exosomes promote skin flap survival by enhancing angiogenesis, with HIF1AN/HIF-1α/VEGFA playing a crucial role in this process.

Hypoxic mesenchymal stem cell-derived exosomes promote the survival of skin flaps after ischaemia-reperfusion injury via mTOR/ULK1/FUNDC1 pathways.

Flap necrosis, the most prevalent postoperative complication of reconstructive surgery, is significantly associated with ischaemia-reperfusion injury. Recent research indicates that exosomes derived from bone marrow mesenchymal stem cells (BMSCs) hold potential therapeutic applications in several diseases. Traditionally, BMSCs are cultured under normoxic conditions, a setting that diverges from their physiological hypoxic environment in vivo. Consequently, we propose a method involving the hypoxic preconditioning of BMSCs, aimed at exploring the function and the specific mechanisms of their exosomes in ischaemia-reperfusion skin flaps. This study constructed a 3 × 6 cm2 caudal superficial epigastric skin flap model and subjected it to ischaemic conditions for 6 h. Our findings reveal that exosomes from hypoxia-pretreated BMSCs significantly promoted flap survival, decrease MCP-1, IL-1ß, and IL-6 levels in ischaemia-reperfusion injured flap, and reduce oxidative stress injury and apoptosis. Moreover, results indicated that Hypo-Exo provides protection to vascular endothelial cells from ischaemia-reperfusion injury both in vivo and in vitro. Through high-throughput sequencing and bioinformatics analysis, we further compared the differential miRNA expression profiles between Hypo-Exo and normoxic exosomes. Results display the enrichment of several pathways, including autophagy and mTOR. We have also elucidated a mechanism wherein Hypo-Exo promotes the survival of ischaemia-reperfusion injured flaps. This mechanism involves carrying large amounts of miR-421-3p, which target and regulate mTOR, thereby upregulating the expression of phosphorylated ULK1 and FUNDC1, and subsequently further activating autophagy. In summary, hypoxic preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of BMSC-derived exosomes in the treatment of flap ischaemia-reperfusion injury.

Substance P promote macrophage M2 polarization to attenuate secondary lymphedema by regulating NF-kB/NLRP3 signaling pathway.

Secondary lymphedema often occurs after filariasis, trauma, lymph node dissection and radiation therapy, which is manifested by infiltration of inflammatory cells and fibrosis formation in pathologically. Substance P is a widely used neuropeptide in the field of tissue repair, while the regenerative potential of the substance P has not been proven in the secondary lymphedema. In this study, animal model of secondary lymphedema was constructed by excising the skin and subcutaneous lymphatic network in the tail of mice, and the degree of swelling in the tail of mice was evaluated after 6 weeks under the treatment with substance P. Immunofluorescence staining was also performed to assess immune cell infiltration, subcutaneous fibrosis and lymphangiogenesis. The results revealed that substance P significantly alleviated post-surgical lymphedema in mice. Furthermore, we found that substance P promoted macrophages M2 polarization, a process associated with downregulation of the NF-kB/NLRP3 pathway. After application of disodium clodronate (macrophage scavenger, CLO), the positive effect of substance P in lymphedema is significantly inhibited. In vitro experiments, we further demonstrated the polarizing effect of substance P on bone marrow-derived macrophages (BMDMs), while substance P inhibited the activation of the NF-kB/NLRP3 pathway in BMDMs after the treatment of lipopolysaccharide (LPS). In addition, polarized macrophages were demonstrated to promote the proliferation, tube-forming and migratory functions of human lymphatic endothelial cells (hLEC). In conclusion, our study provides preliminary evidence that substance P alleviates secondary lymphedema by promoting macrophage M2 polarization, and this therapeutic effect may be associated with downregulation of the NF-kB/NLRP3 pathway.

Efficacy comparison of vascularized iliac crest bone flap and Ilizarov bone transport in the treatment of traumatic bone defects of the tibia combined with large soft tissue defects.

BACKGROUND: Traumatic tibial defect complicated with soft tissue defect is a difficult problem in clinic. Vascularized iliac crest bone flap (VIBF) and Ilizarov bone transport are effective methods to treat tibial defects with limited defect length, which most need to be explored accordingly. METHODS: In this study, a total of 68 patients with traumatic tibial defect (ranging from 4 to 10 cm) and large soft tissue defect were collected retrospectively. The soft tissue defects were repaired by latissimus dorsal musculocutaneous flap (LD), anterolateral thigh flap (ALTF) or both. Thirty-three cases were treated with vascularized iliac crest bone flap transplantation and 35 cases were treated with Ilizarov bone transport. Intraoperative and postoperative follow-up data (including operation time, blood loss, bone union time, external fixation time, external fixation index, complication rate, reoperation rate, and functional evaluation) were recorded, and comparative analysis was performed. RESULTS: The median follow-up time was 32 months. Compared with Ilizarov group, the VIBF group exhibited statistically faster bone union time (6.3 ± 1.0 vs. 18.2 ± 3.0 months). Moreover, the VIBF group showed shorter EFT (7.3 ± 1.0 vs. 19.2 ± 3.0 months) and a better EFI (34.8 ± 9.2 vs. 84.2 ± 23.7 days/cm). The excellent and good rate of lower limb appearance evaluation in VIBP group was significantly better than that in Ilizarov group. The complication rate and reoperation rate were significantly higher in Ilizarov group. CONCLUSION: In summary, compared with Ilizarov bone transport, VIBP has the advantages of faster healing, shorter external fixation time, lower complication and reoperation rate, and better appearance within the limited defect length. Ilizarov bone transport is still preferred when the defect length exceeds the maximum repair length of the iliac flap. The daily handling required by bone transport process is painful. LEVEL OF EVIDENCE: III, Case-control study.

The research landscape on vascularized composite allografts: a bibliometric analysis (2002-2021).

OBJECTIVE: Vascularized composite allografts (VCAs) refer to the transplantation of multiple types of tissues during plastic and reconstructive surgery. Several publications have emerged in the field of VCA. However, there are no bibliometric studies on this topic. The aim was to multidimensionally analyze the knowledge base and hotspots in this subject. METHODS: We retrieved all publications related to VCA from the Web of Science Core Collection (WoSCC), published from 2002 to 2021. Next, scientometric analysis of different items was performed using various bibliometrics software to explore knowledge base, research hotspots, and advancement trends in this field. RESULTS: We included a total of 3,190 English articles from 2002 to 2021. The number of publications increased steadily annually. The United States produced the highest number of publications, followed by China. Most publications were from Harvard University, followed by Johns Hopkins University. The most authoritative academic journal was Plastic and Reconstructive Surgery. Transplantation occupied the first rank of co-cited journal list. Maria Z Siemionow may have the highest influence in the VCA field with the highest number of citations (n = 88) and co-cited references (n = 1252). Clinical studies on different allografts, immunosuppression, and tissue engineering were both the knowledge base and recent topics in VCA research. CONCLUSIONS: The first bibliometric study comprehensively summarized the trends and development of VCA research with steady growth over the past two decades. Currently, the most active topics are the clinical application of multiple allografts, immunosuppression strategies/therapies, and translation of tissue engineering to clinical practice.

Transcriptomic responses of the liver of mandarin fish (Siniperca chuatsi) under hypoxic stress.

Environmental hypoxia is becoming more prevalent in aquatic environments of mandarin fish (Siniperca chuatsi) aquaculture because of eutrophication and climate change. Little information is available on the molecular mechanisms of the detrimental effects of hypoxia in this species. In this study, the authors assembled a transcriptome for mandarin fish exposed to lower oxygen conditions at different times (24 and 96 h). The antioxidant enzymatic activities of catalase, glutathione, superoxide dismutase, glutamic pyruvic transaminase and malondialdehyde significantly increased at 6 or 12 h but decreased after reaching a climax during 96 h hypoxia stress. The gene ontology study revealed 27,616 transcripts, whereas the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed 25 linked pathways. Significant changes in the expression of certain genes involved in protein processing in the endoplasmic reticulum, the calcium signalling system and inositol phosphate metabolism were discovered using the KEGG pathway analysis. In the liver, 97 genes were differentially expressed between the control and experimental groups. The expression level of 28 differentially expressed genes (DEGs) under different hypoxic stress conditions was detected using real-time PCR and compared to transcriptome sequencing results. The result showed that some genes in the experimental group associated with hypoxic stress, such as hif, ho-1a, ho-1b, igfbp1, hsp90α and hsp90 ß, were significantly upregulated compared with those in the control group. The large amount of transcriptome data from this research has enlarged the mandarin fish gene and genome bioinformation. The identified DEGs and pathways are useful in further studies of biological responses to hypoxia.

Comparison of retrograde anatomy iliac bone flap grafting versus anterograde anatomy iliac bone flap grafting for treatment of osteonecrosis of the femoral head.

BACKGROUND: Iliac bone flap with deep circumflex iliac artery is a common option in the treatment of Osteonecrosis of the femoral head (ONFH), and dissection of iliac bone flap is the key step for successful operation. This paper aims to introduce a new operative technique for dissecting iliac bone flap with deep circumflex iliac artery based on analysis of its advantages. METHODS: A total of 49 patients treated by retrograde anatomy and 52 patients treated by anterograde anatomy from January 2010 to December 2020 were recruited. The two groups were then compared in terms of the preoperative baseline conditions, intraoperative data, and postoperative Harris hip score (HHS). RESULTS: Compared with the retrograde anatomy group, the anterograde anatomy group had a significantly longer operating time, a significantly heavier intraoperative blood loss, a significantly higher rate of donor complication morbidity, a significantly higher rate of donor-recipient delayed healing, a significantly higher failure rate of iliac bone flap resection, a significantly higher rate of lateral femoral cutaneous nerve (LFCN) injury, and a significantly higher rate of ectopic ossification. No difference was found in postoperative HHS score between the two groups. CONCLUSION: As a new operative technique that can accurately locate the nutrient vessels of the iliac bone flap and quickly dissect the iliac bone flap with deep circumflex iliac artery while maintaining a comparable clinical effect, retrograde anatomy exhibited distinct advantages over anterograde anatomy in terms of simpler intraoperative operation, safer dissection, shorter operation time, lower blood loss, and fewer donor complications. LEVEL OF EVIDENCE: III, Retrospective.

Ilizarov Bone Transfer for Treatment of Large Tibial Bone Defects: Clinical Results and Management of Complications.

BACKGROUNDS: The purpose of this study is to present our clinical experience using the Ilizarov bone transfer technique and free-flap technique in the reconstruction of large tibial bone and soft tissue defects, including an evaluation of both the management of postoperative complications and long-term outcomes. METHODS: From January 2010 to May 2020, 72 patients with tibia bone and soft tissue defects were retrospectively evaluated. Either an anterolateral thigh perforator flaps (ALTP) or latissimus dorsi musculocutaneous flaps (LD), solely or in combination, were used to cover soft tissue defects. Once the flap was stabilized, an Ilizarov external fixator was applied to the limb. Follow-up was postoperatively performed at 1, 3, 6, 9, and 12 months. RESULTS: Postoperatively, there were two cases of total and five of partial flap necrosis, and two cases of subcutaneous ulcers, which were caused by vascular crisis, infection, and hematoma, respectively. All the patients underwent Ilizarov external fixator surgery after flap recovery. A total of 16 complications occurred, including 3 cases of simple needle tract infection (antibiotic treatment) and 13 cases of complications requiring reoperation. A correlation factor analysis revealed that the main factors affecting the healing time were the defect length and operative complications. All patients with complications treated with the vascularized iliac flap eventually healed completely. CONCLUSIONS: The Ilizarov method used together with an ALTP, LD, or a combination thereof yields good clinical results for repairing large bone and soft tissue defects of the tibia, thus reducing the incidence of amputations. However, longer treatment times may be involved, and postoperative complications can occur. The vascularized iliac flap may be a suitable choice for the treatment of postoperative complications of this type of Ilizarov bone transport.

Early Reconstruction Delivered Better Outcomes for Severe Open Fracture of Lower Extremities: A 15-Year Retrospective Study.

Background: The principle of early flap reconstruction for high-grade traumatic lower-extremity injuries established in 1986 by Godina has been widely accepted. However, the lack of an orthoplastic center in China makes early reconstruction not accessible for all patients with a Gustilo IIIB fracture. This study aimed to analyze the impact of timing on outcomes in lower-extremity traumatic free-flap reconstruction. Methods: A retrospective review identified 394 free-flap reconstructions performed from January 2005 to January 2020 for Gustilo IIIB tibial fractures. Patients were stratified based on the number of debridements: two times or less (early) and more than two times (delayed). The interval between injury and reconstruction, surgery time, hemorrhage volume, length of hospitalization (LoS), wound and bone healing time, flap outcomes, and function restoration were examined based on times of debridement. Results: The mean interval between injury and flap reconstruction in the early-repair group with 6.15 ± 1.82 postoperative days (PODs) was significantly shorter than that of the delayed-repair group with 16.46 ± 4.09 PODs (p < 0.001). The flap harvest time, reconstructive time, and intraoperative blood loss were also significantly less in the early-repair group compared to the delayed-repair group. Interestingly, we observed an 8.20% enlargement of wound size due to multiple debridements in the delayed-repair group. Most importantly, the early-repair group had better outcomes with a decreased risk of total or partial flap necrosis, lower incidence of flap complications, and fewer overall late complications than the delayed-repair group. In addition, the LoS, as well as wound and bone healing time, were notably shorter in the early-repair group. Furthermore, 4.85% of cases in the delayed-repair group experienced additional operations on bone, while no additional operations were performed in the early-repair group. All cases in both groups obtained satisfying functional results, while the early-repair group showed better functional recovery. Conclusions: Early repair with free flaps performed within two instances of debridement had superior outcomes when compared with delayed reconstruction after multiple debridements, consistent with Godina's findings. We recommended early referral to a higher-level hospital with orthoplastic capabilities after an aggressive and thorough initial debridement carried out by senior surgeons.

Knock-down of amh transcription by antisense RNA reduces FSH and increases follicular atresia in female Oreochromis niloticus.

Anti-Müllerian hormone (Amh) plays an important role in regulating gonad development in teleosts. However, little is known about the effects of Amh on follicle development. In this study, we transfected the vector containing antisense RNA fragments of the amh gene to produce Nile tilapia, Oreochromis niloticus, with knocked-down Amh function in vivo. The results confirmed that the antisense RNA effectively inhibited amh transcription and Amh protein expression in female tilapia ovarian tissue. At 180 days of age, compared with control fish, female tilapia with knocked-down Amh function showed significantly increased growth and significantly decreased ovary weight and gonadosomatic index (P < 0.05). Female fish in the control group had ruddy-colored external genitalia, eggs extruded from the abdomen when gently squeezed, and most oocytes were developmental stage V. In contrast, the external genitalia of female fish with knocked-down Amh function did not have the ruddy color, no eggs extruded from the abdomen when squeezed, most oocytes were at developmental stages II and III, and considerable follicular atresia was apparent. At 180 days of age, the transcript levels of amhrII, cyp19a1a, foxl2 and sox9b in ovarian tissue, and the titers of luteinizing hormone, follicle stimulating hormone, and estradiol in the serum, were significantly lower in fish with knocked-down Amh function than in control fish (P < 0.05). We concluded that decreased serum hormone levels and an abnormal AMH signal delayed development and caused follicular degeneration in Nile tilapia with knocked-down Amh function. These findings show that antisense RNA is a feasible approach for gene silencing in fish, and represents an accurate and effective strategy to study gene function.

Derivation of Stem Cell-like Cells From Spherical Culture of Astrocytes for Enhanced Neural Repair After Middle Cerebral Artery Occlusion.

Neural precursor cells (NPCs) tend to aggregate and develop into three-dimensional (3D) spheres, which in turn help maintain the stemness of the cells. This close relationship between spherical environments and cell stemness direct us to assume that 3D spheres of astrocytes (ASTs) may facilitate the acquisition of stem cell-like features and generate sufficient seed cells for the regeneration of neurons. In vitro results confirmed that mouse ASTs cultured on agarose surfaces spontaneously formed cell spheres and exhibited molecular features similar to stem cells, particularly capable of further differentiating into neurons and forming functional synaptic networks with synchronous burst activities. RNA-sequencing results revealed the similarity between AST-derived stem cells (A-iSCs) and NPCs in global gene expression profiles. The potency of A-iSCs in repairing neural injuries was evaluated in a mouse model of middle cerebral artery occlusion. It was observed that the transplanted A-iSCs expressed a series of markers related to neural differentiation, such as NeuN, Tuj1, and Map2, indicating the conversion of the transplanted A-iSCs into neurons in the scenario. We also found that the injured mice injected with A-iSCs exhibited significant improvements in sensorimotor functions after 8 weeks compared with the sham and control mice. Taken together, mouse ASTs form cell spheres on agarose surfaces and acquire stem cell-associated features; meanwhile, the derived A-iSCs possess the capacity to differentiate into neurons and facilitate the regeneration of damaged nerves.

Transcriptional inhibition of steroidogenic factor 1 in vivo in Oreochromis niloticus increased weight and suppressed gonad development.

Steroidogenic factor 1 (sf1) (officially designated as nuclear receptor subfamily 5 group A member 1 [NR5A1]) is an important regulator of gonad development. Previous studies on sf1 in fish have been limited to cloning and in vitro expression experiments. In this study, we used antisense RNA to down-regulate sf1 transcription and sf1 protein expression. Down-regulation of sf1 resulted in an increase in body weight and inhibition of gonadal development in both males and females with the consequent lower gonadosomatic index compared to fish in the control group. Hematoxylin-eosin staining of the gonads of fish with down-regulated sf1 revealed fewer seminiferous tubules and sperm in the testis of males. In addition, the oocytes were mainly stage II and many of them were atretic follicle. We conducted comparative transcriptome and proteome analyses between the sf1-down-regulated group and the control group. These analyses revealed multiple gene-protein pairs and pathways involved in regulating the observed changes, including 44 and 74 differently expressed genes and proteins in males and females, respectively. The results indicated that dysfunctional retinal metabolism and fatty acid metabolism could be causes of the observed weight gain and gonad abnormalities in sf1-down-regulated fish. These findings demonstrate the feasibility of using antisense RNA for gene editing in fish. This methodology allows the study gene function in species less amenable to gene editing as for example aquaculture species with long life cycles.

FK506-loaded PLGA nanoparticles improve long-term survival of a vascularized composite allograft in a murine model.

BACKGROUND: The side effects of life-long administration of FK506 limit the clinical practice of vascularized composite allografts (VCAs). This study aimed to evaluate the feasibility of FK506-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (FK506 NPs) for prolonging the long-term survival of VCAs and reducing the side effects of FK506. METHODS: PLGA nanoparticles loaded with FK506 were prepared by the solvent evaporation method. The characterization of FK506 NPs was evaluated by electron microscopy. To confirm the function and safety of FK506 NPs, these particles were administrated into rats by intraperitoneal injection. The survival time of the allograft, systemic concentration of FK506, anti-rejection activity, and side-effect of FK506 NPs were evaluated in a Brown Norway (BN)-to-Sprague Dawley (SD) epigastric VCA transplantation model. RESULTS: Compared with the nontreatment, PLGA control and FK506 groups, the median survival times (MST) of the FK506 NP groups were significantly prolonged. The FK506 NPs could maintain therapeutic drug concentration for 60 days. Moreover, cytokine concentrations, flow cytometry of regulatory T cells (Tregs) and histopathology of allografts revealed significantly prolonged immunosuppression by FK506 NPs. FK506 NPs also ameliorated FK506 nephrotoxicity. CONCLUSIONS: FK506 NPs prolong the survival time of VCAs in a murine model with minimal nephrotoxicity, and provide a potential clinical strategy for ameliorating long-term side effects of immunosuppressive therapy.

A Chromosome-Level Genome Assembly of the Mandarin Fish (Siniperca chuatsi).

The mandarin fish, Siniperca chuatsi, is an economically important perciform species with widespread aquaculture practices in China. Its special feeding habit, acceptance of only live prey fishes, contributes to its delicious meat. However, little is currently known about related genetic mechanisms. Here, we performed whole-genome sequencing and assembled a 758.78 Mb genome assembly of the mandarin fish, with the scaffold and contig N50 values reaching 2.64 Mb and 46.11 Kb, respectively. Approximately 92.8% of the scaffolds were ordered onto 24 chromosomes (Chrs) with the assistance of a previously established genetic linkage map. The chromosome-level genome contained 19,904 protein-coding genes, of which 19,059 (95.75%) genes were functionally annotated. The special feeding behavior of mandarin fish could be attributable to the interaction of a variety of sense organs (such as vision, smell, and endocrine organs). Through comparative genomics analysis, some interesting results were found. For example, olfactory receptor (OR) genes (especially the beta and delta types) underwent a significant expansion, and endocrinology/vision related npy, spexin, and opsin genes presented various functional mutations. These may contribute to the special feeding habit of the mandarin fish by strengthening the olfactory and visual systems. Meanwhile, previously identified sex-related genes and quantitative trait locis (QTLs) were localized on the Chr14 and Chr17, respectively. 155 toxin proteins were predicted from mandarin fish genome. In summary, the high-quality genome assembly of the mandarin fish provides novel insights into the feeding habit of live prey and offers a valuable genetic resource for the quality improvement of this freshwater fish.

Comparison of free vascularized iliac bone flap grafting versus pedicled iliac bone flap grafting for treatment of osteonecrosis of the femoral head.

BACKGROUND: A high incidence of osteonecrosis of the femoral head (ONFH), a commonly seen and intractable disease, has been reported. This retrospective study aims to compare the reconstructive outcomes by free vascularized iliac bone flap (FVIBF) with those by vascularized pedicled iliac bone flap (PIBF) to determine which one is better for ONFH patients. METHODS: From January 2010 to December 2017, 35 patients (40 hips) were treated by PIBF grafting, and 32 patients (36 hips) were treated by FVIBF grafting. The two groups were then compared in terms of the preoperative baseline conditions, intraoperative data, and postoperative Harris hip score (HHS). RESULTS: In the PIBF group, the operating time was significantly longer than the FVIBF group (195.5 ±â€¯26.4 vs 147.2 ±â€¯17.7 min, respectively), and the intra-operative blood loss was significantly heavier (330.0 ±â€¯63.9 vs 240.3 ±â€¯37.5 ml, respectively). Meanwhile, the recipient site morbidity rate in the PIBF group outnumbered that in the FVIBF group (27.5% vs 8.3%, respectively), and a higher rate of lateral femoral cutaneous nerve (LFCN) injury was observed in the PIBF group than in the FVIBF group (27.5% vs 8.3%, respectively). No difference was found in postoperative HHS score between the two groups. In both groups, the recovery effect of the patients in stage II was better than that in stage III. CONCLUSION: While maintaining a similar clinical effect, the FVIBF grafting exhibited a distinct advantage over the PIBF grafting, in terms of shorter operative time, less blood loss, and lower risk of LFCN injury.

Individualized design of double skin paddle anterolateral thigh perforator flaps to repair complex soft tissue defects of the extremities: An anatomical study and retrospective cohort study.

This study describes our experience using individually designed double skin paddle anterolateral thigh perforator (ALTP) flaps to reconstruct complex soft tissue defects. An anatomical study of double skin paddle ALTP flaps was conducted in six fresh cadavers (12 thighs). We also performed a retrospective cohort study of 36 patients who underwent reconstruction using double skin paddle ALTP flaps from January 2009 to June 2019. The soft tissue defects were large or non-adjacent defects that could not be repaired by a single flap. Three types of double skin paddle ALTP flaps were designed. In type I, separate perforators supplied each flap: one perforator from the transverse branch of the lateral circumflex femoral artery (LCFA) and one from the descending branch of the LCFA (d-LCFA). In type II, both perforators were from the d-LCFA. In type III, a single perforator from the d-LCFA had two branches that each supplied one flap. In the cadaver study, type I was observed in 11 thighs, type II in 10, and type III in six. All patients were successfully treated using double skin paddle ALTP flaps. Four patients received type I flaps, 23 received type II, and nine received type III. Vascular compromise occurred in one patient, and the flap was saved by emergency revascularization. Most patients had satisfactory contours and functional recovery during follow-up. Individually designed double skin paddle ALTP flaps is a reliable option for reconstructing complex soft tissue defects. Moreover, we created an algorithm for microvascular reconstruction of complex soft tissue defects.

Outcomes of free anterolateral thigh perforator flaps versus free modified latissimus dorsi myocutaneous flaps for Gustilo type IIIB open tibial fractures with necrosis and infection.

BACKGROUND: Infection and non-union of fractures are potential complications of Gustilo type IIIB open tibial fractures. It is important to choose the most effective type of flap to reduce the incidence of infection and non-union. METHOD: This study reviewed outcomes of 44 patients (aged 16-65 years) who underwent reconstruction of Gustilo type IIIB tibial fractures from January 2004 to January 2017. Patients received a free anterolateral thigh perforator flap (ALTP; n = 23) or modified latissimus dorsi myocutaneous flap (MLD; n = 21). Demographic data, intraoperative data, postoperative complications, and long-term outcomes were compared between groups. RESULTS: Flap complications occurred in 8 patients (18.2%) after flap reconstruction: 6 in the ALTP group and 2 in the MLD group (P < 0.05). No patient developed total flap necrosis. Rates of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) normalization were higher in the MLD group than in the ALTP group at 2 and 4 weeks after flap transfer (P < 0.05). By 6 months, fracture union occurred in 52.4% of patients in the MLD group and 30.4% of those in ALTP group (P < 0.05). By 9 months, union occurred in 85.7% of MLD group patients and 52.2% of MLD group patients (P < 0.05). CONCLUSION: MLD was associated with fewer flap complications, shorter time to ESR and CRP normalization, and higher union rates by 6 and 9 months, compared with ALTP. These results suggest that MLD may provide a better environment for reducing susceptibility to infection and promoting fracture healing in Gustilo type IIIB tibial fractures with necrosis and infection.

A comparative study for the rate of adverse outcomes in unilateral and bilateral abdominal flap breast reconstruction: A meta-analysis.

BACKGROUND: Adverse outcomes after unilateral vs bilateral breast reconstruction involve an unknown level of risk that warrants thorough investigation. METHODS: To address this research need, PubMed, Ovid, Medline, EMBASE, and Scopus databases were searched through systematically from January 1, 1990, to January 1, 2019 to retrieve the relevant studies on the risk of postoperative complications after unilateral vs bilateral abdominal flap breast reconstruction. According to the pre-designed inclusion criteria, available data were extracted from the relevant studies, and then analyzed comparatively in order to identify the relative risk (RR) and 95% confidence intervals (CI) applying either a random or a fixed effects model. RESULTS: Eventually, 20 studies involving 8122 female subjects met the inclusion criteria. It was found that unilateral reconstruction involved a significantly higher risk of flap loss (RR: 1.56, 95% CI: 1.21-2.00; P < .05) and fat necrosis (RR: 1.60, 95% CI: 1.23-2.09; P < .05) compared to bilateral reconstruction, while bilateral reconstruction involved a greater risk of abdominal hernia/bulge (RR: 1.67, 95% CI: 1.25-2.24; P < .05). The risk was found to be higher following bilateral free transverse rectus abdominis myocutaneous (fTRAM) flaps in comparison with deep inferior epigastric perforator (DIEP) flaps (RR: 2.62, 95% CI: 1.33-5.15; P < .05). CONCLUSION: The risk of postoperative flap complications in unilateral breast reconstruction is significantly higher than that in bilateral reconstruction. Contrarily, the abdominal complications were significantly higher in the bilateral group vs the unilateral group. Meanwhile, the risk of abdominal hernia/bulge complication after bilateral breast reconstruction was significantly higher with fTRAM vs DIEP. Therefore, DIEP flaps are recommended in priority for bilateral breast reconstruction, unless specifically contraindicated.

Extracellular vesicles from human urine-derived stem cells inhibit glucocorticoid-induced osteonecrosis of the femoral head by transporting and releasing pro-angiogenic DMBT1 and anti-apoptotic TIMP1.

Osteonecrosis of the femoral head (ONFH) frequently occurs after glucocorticoid (GC) treatment. Extracellular vesicles (EVs) are important nano-sized paracrine mediators of intercellular crosstalk. This study aimed to determine whether EVs from human urine-derived stem cells (USC-EVs) could protect against GC-induced ONFH and focused on the impacts of USC-EVs on angiogenesis and apoptosis to explore the mechanism by which USC-EVs attenuated GC-induced ONFH. The results in vivo showed that the intravenous administration of USC-EVs at the early stage of GC exposure could rescue angiogenesis impairment, reduce apoptosis of trabecular bone and marrow cells, prevent trabecular bone destruction and improve bone microarchitecture in the femoral heads of rats. In vitro, USC-EVs reversed the GC-induced suppression of endothelial angiogenesis and activation of apoptosis. Deleted in malignant brain tumors 1 (DMBT1) and tissue inhibitor of metalloproteinases 1 (TIMP1) proteins were enriched in USC-EVs and essential for the USC-EVs-induced pro-angiogenic and anti-apoptotic effects in GC-treated cells, respectively. Knockdown of TIMP1 attenuated the protective effects of USC-EVs against GC-induced ONFH. Our study suggests that USC-EVs are a promising nano-sized agent for the prevention of GC-induced ONFH by delivering pro-angiogenic DMBT1 and anti-apoptotic TIMP1. STATEMENT OF SIGNIFICANCE: This study demonstrates that the intravenous injection of extracellular vesicles from human urine-derived stem cells (USC-EVs) at the early stage of glucocorticoid (GC) exposure efficiently protects the rats from the GC-induced osteonecrosis of the femoral head (ONFH). Moreover, this study identifies that the promotion of angiogenesis and inhibition of apoptosis by transferring pro-angiogenic DMBT1 and anti-apoptotic TIMP1 proteins contribute importantly to the USC-EVs-induced protective effects against GC-induced ONFH. This study suggests the promising prospect of USC-EVs as a new nano-sized agent for protecting against GC-induced ONFH, and the potential of DMBT1 and TIMP1 as the molecular targets for further augmenting the protective function of USC-EVs.