BackgroundThis study aimed to investigate the role of myofiber-specific TGF-β signaling in the development of muscle inflammation by modulating Treg-cell-mediated macrophage efferocytosis.MethodsCTX-induced muscle injury was performed in the tibialis anterior (TA) of control (TGF-βr2flox/flox) and transgenic mice with skeletal muscle-specific deletion of TGF-β receptor 2 (SM TGF-βr2−/−). Gene levels of regulatory T cell (Treg) activation markers and inflammatory mediators produced by macrophages or Tregs were assessed using qRT-PCR. Intramuscular infiltration of Tregs and macrophages, as well macrophage phenotypes, efferocytic function, and associated signaling molecules, were evaluated using hematoxylin and eosin (HE) staining, immunofluorescence, immunoblotting and FACS analysis. The correlation of myofibers with Tregs-mediated macrophage efferocytosis were addressed under an in vitro co-culture system, which including Tregs, macrophages, and the differentiated myogenic precursor cells (MPC-myotubes) isolated from control or SM TGF-βr2−/−mice. Apoptotic cells were generated by UV irradiation prior to transfer into inflamed muscle.ResultsDeficiency in muscle TGF-β signaling resulted in more severe muscle inflammation, characterized by an increased number of M1 macrophages and a decreased number of M2 macrophages. Notably, the absence of muscle TGF-β signaling impaired the efferocytic capacity of macrophages and reduced the proportion of Tregs in inflamed muscle. Further, we monitored that activation of intrinsic TGF-β signaling suppresses myofiber IL-6 production, which in turn impacted on IL-13 production from Tregs accumulated in damaged muscle. This ultimately facilitates IL-10-STAT3-Vav1-mediated macrophage efferocytosis in inflamed muscle.ConclusionsOur findings establish a link between muscle-specific TGF-β signaling, myokine IL-6, Tregs derived IL-13 and macrophage efferocytosis in inflamed muscle. These results suggest that therapeutic targeting of this axis may hold promise for promoting muscle regeneration.

OBJECTIVE:To develop electrospun polycaprolactone/gelatin (P/G) nanofibers modified with epigallocatechin gallate‑selenium nanoparticles (EGCG@Se) and evaluate their osteogenic effects in vitro and in vivo. METHODS:P/G nanofibers were fabricated by electrospinning, and EGCG@Se nanoparticles were synthesized using cysteine as a reducing agent. Composite fibers were formed by surface deposition and characterized using SEM, WCA, EDS, FTIR, AFM, and mechanical tests. In vitro, MSCs and MC3T3-E1 cells were cultured on P/G-EGCG@Se fibers under osteogenic induction. A tibial defect model in KM mice was used for in vivo osteogenic evaluation. Gene and protein expression were analyzed by qPCR, Western blot and ELISA. RESULTS:P/G fibers with an 8:2 weight ratio and 12 kV voltage exhibited optimal properties. EGCG@Se enhanced MSCs viability, adhesion and osteogenic differentiation. In vitro, 7.5 μg/mL Se-loaded fibers showed the best osteoinductive effect. However in vivo, 15 μg/mL Se-loaded fibers resulted in the optimal tibial defect repair, which significantly suppressed IL-6 expression in skeletal muscle. In vitro co-culturing test demonstrated that Se content in P/G-EGCG@Se nanofibers controls IL-6 production in muscle fibers. CONCLUSIONS:The special physicochemical properties of P/G-EGCG@Se fibers, assisted by bone repair effects of EGCG, and by the optimal Se content induced IL-6 level reduction from muscle tissue, contribute to the efficient bone defect healing in vivo.

With the growing interest in skeletal muscle diseases, understanding the processes, factors, and treatments associated with muscle regeneration is crucial. Skeletal muscle regeneration is a complex process that largely depends on the niche composed of cell populations, such as satellite cells, and their microenvironment. Cellular senescence is associated with various physiological processes and age-related diseases and plays a significant role in the muscle regeneration niche. Deciphering senescence-associated alterations within this niche provides critical insights for developing targeted anti-aging therapies. This review synthesizes recent studies to elucidate the composition of the niche and its cell-cell interactions and outlines the effects of aging on muscle regeneration and corresponding therapeutic strategies. This review summarizes emerging findings and technologies in muscle regeneration, analyzing therapeutic potential and limitations of current approaches for age-related conditions to support research advancement.

To enhance the biocompatibility and drug delivery efficiency of graphene oxide (GO), poly(ethylene glycol) (PEG), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), or its triblock copolymer PEG-PHBV-PEG (PPP) were used to chemically modify GO. However, it is still unknown whether non-toxic polymer-modified GO mediates muscle toxicity or triggers intramuscular inflammation. This study aims to investigate the biological reactivity and inflammation/immune response induced by PEG, PHBV, or PPP modified GO when injected into the tibialis anterior (TA) muscle of mice prior to drug loading. The results showed that after muscle exposure, the coating of biocompatible polymers on GO is more likely to provoke muscle necrosis. Muscle regeneration was found to occur earlier and more effectively in muscle treated with hydrophilic PEG-GO and PPP-GO compared to muscle treated with hydrophobic PHBV-GO. When observing the transient muscle macrophage invasion of three modified GOs, PHBV-GO caused severe muscle necrosis in the early stage, induced a delayed peak of macrophage aggregation, and caused severe inflammatory progression. All three kinds of modified GO induced T cell aggregation to varying degrees, but PEG-GO induced early mass muscle recruitment of CD4+ T cells and was more sensitive to cytotoxic T cells. Based on the higher biocompatibility of PPP-GO in muscles, PPP-GO was implanted into the muscles of old or adult mice. Compared to adult mice, aged mice are more vulnerable to the stress from PPP-GO, as demonstrated by a delayed inflammatory response and muscle regeneration.

Backgroud:Reduction of valgus-impacted femoral neck fractures remains a major challenge for orthopedic surgeons. Most reduction techniques require extensive surgical experience, and intraoperative reduction evaluation standards do not exist. The aim of this study is to report the use of a noninvasive extracapsular traction reduction technique for valgus-impacted femoral neck fractures and our innovative use of a smartphone application to evaluate reduction outcomes. Methods:We conducted a retrospective study on patients with valgus-impacted femoral neck fractures who underwent the noninvasive extracapsular traction reduction technique at a hospital between December 2022 and January 2024. General medical records from the preoperative, intraoperative, and postoperative periods were collected, with particular emphasis on evaluating intraoperative reduction effectiveness. The primary reduction indicator was the reduction angle (RA). The principal functional assessment indicator was the Harris Hip Score (HHS). Results:Radiographic measurements demonstrated significant differences between preoperative and postoperative RAs on the affected side (p < 0.05), while no differences in the RAs were observed between the unaffected side and postoperative affected side (p > 0.05). No statistically significant difference was detected between the intraoperative and postoperative radiographic measurements of the RAs on the affected side (p > 0.05). The follow-up period ranged from 12 to 25 months, with a mean duration of 17.7 ± 3.5 months. Preoperative HHS averaged 37.9 ± 5.2 points, increasing to 88.7 ± 4.1 points at final follow-up. Both 6-month and 1-year postoperative HHS showed significant improvement compared to preoperative values (p < 0.05). No fixation failure was observed during the follow-up, with a radiographic failure rate of 0% at final assessment. Conclusions:For valgus-impacted femoral neck fractures, the bone hook-assisted noninvasive extracapsular traction reduction technique can achieve optimal reduction without causing intraarticular cartilage damage. The RA helps evaluate the quality of intraoperative reduction. ImageMeter can be an effective tool for evaluating fracture reduction intraoperatively.

The descending genicular artery (DGA) and medial thigh region have been underused as donor sites for perforator flaps. This study evaluated the anatomical relationship between the perforators of the DGA and the saphenous vein (SV) to review the clinical applications of the free descending genicular artery perforator (DGAP) flap for locoregional reconstruction. Fifteen cadavers were arterially perfused with red latex and dissected. Thirty-one patients with extremity tissue defects were treated with a free DGAP flap, including six patients who received a chimeric flap. The minimum distance between the DGAP and the SV was measured during surgery. In all patients, the skin branch of the descending genicular artery was found in the medial femoral condyle plane in front of the SV. The average distance between the descending genicular artery perforator and the SV was 3.71 ± 0.38 cm (range: 2.9–4.3 cm). Thirty flaps survived completely, and one flap developed partial necrosis; however, this flap healed two weeks after skin grafting. The average follow-up time was 11.23 months. We conclude that the SV can be preserved when harvesting the descending genicular artery perforator flap, causing less damage to the donor site and having no effect on flap survival. The free descending genicular artery perforator flap without the SV is a better therapy for complicated tissue defects.

[This corrects the article DOI: 10.3389/fmolb.2022.983410.].

To explore the role of skeletal muscle specific TGF-β signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection. CTX myoinjury was manipulated in TGF-βr2flox/flox (control) mice or transgenic mice with TGF-β receptor 2 (TGF-βr2) being specifically deleted in skeletal muscle (SM TGF-βr2−/−). Gene levels of TGF-β signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-β pathway molecules, myokines and embryonic myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation. In control mice, TGF-β-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-β signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-β signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V−F4/80+Tunel+ macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67+ apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-β signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages. Our data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-β signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis.

Background Minimally invasive reduction and fixation of intra‐articular calcaneal fractures poses great challenges for orthopaedic surgeons. The aim of the present study was to report the technical points, evaluate the efficacy of minimally invasive reduction and internal fixation assisted by the temporary limb reconstruction system (LRS) external fixator for intra‐articular calcaneal fractures, and propose the indications of our protocol. Methods In this retrospective study, a series of 34 consecutive closed and displaced intra‐articular calcaneal fractures involving the articular surface were treated by this technology between June 2016 and April 2018. X‐ray and computed tomography (CT) scans were performed before and after surgery to measure Bohler's angle; the length, height, and width of the calcaneus; and the mechanical axis of the hindfoot. Postoperative complications were recorded. Imaging and clinical outcomes were comprehensively evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot‐ankle scoring system. After testing the normality of the data, Bohler's angle and the length of calcaneus were compared using the Wilcoxon signed‐rank test. The height, width of the calcaneus, and the mechanical axis of the hindfoot were compared using the Paired‐Samples t‐test. Results Thirty‐two fractures were followed up for an average of 20.66 months (from 12 to 32 months). All fractures achieved stable reduction and bony union. The articular surface was reduced and fixed with direct vision through the sinus tarsi incision. No failure of internal fixation or loss of reduction was detected during follow‐up. There were no soft tissue complications. Bohler's angle; the length, height, and width of the calcaneus; and the mechanical axis of the hindfoot improved significantly. The AOFAS scores averaged 84.12 points; seven cases were rated excellent, 20 good, four fair, and one poor. Conclusions For intra‐articular calcaneal fractures, minimally invasive surgery assisted with temporary LRS external fixation can reconstruct the calcaneal shape and the sub‐talar articular surface. This simple surgical modality with limited complications may be helpful in the surgical treatment of most type II and III calcaneal fractures except comminuted fractures of the calcaneal tuberosity.

Carbon-based nanomaterials have a high specific surface area, biocompatibility, and controlled mesopore structures. These characteristics make carbon nanospheres excellent carriers for drugs, biological dyes, photosensitizers, etc. Nevertheless, little is known about the impact of topological features on the surface of carbon nanomaterials on their in vivo immunoreactivity. In this study, we fabricated mesoporous carbon nanoparticles (MCNs) and solvent-processable carbon vesicles (CVs) by high-temperature calcination. The hematoxylin and eosin (H&E) staining suggested CVs' relatively poor dispersion capacity compared to MCNs and carbon precursors (CPs), leading to more severe muscle inflammation and necrosis. Immunostaining and Fluorescence Activated Cell Sorter (FACS) analysis further showed that both MCNs and CVs triggered a transient immune response in transplanted muscle and muscle-draining lymph nodes, but did not alter muscle resistance to exogenous viruses. In conclusion, this study provides insights into how carbon nanoparticles modulate the activation of immune responses in vivo.

Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are involved in various muscle pathological states. The IRE1α arm of UPR can affect immunological properties of myofiber through restraining p38 mitogen-activated protein kinases (MAPK) activation under inflammatory milieu. However, the relevant pathway molecules regulating the initiation of the IRE1α arm in myofiber remain unclear. In this work, expression of transforming growth factor-beta (TGF-β) and TGF-β receptor II (TGF-βr2), and UPR pathway activation were examined in cardiotoxin (CTX)-damaged mouse muscle, which revealed the activation of TGF-β signaling and UPR in CTX-damaged muscle and in regenerating myofibers. Using control or transgenic mice with TGF-βr2 deleted in skeletal muscle (SM TGF-βr2 −/− ) and the derived primary differentiating myogenic precursor cells (MPCs) treated with/without ERS activator or inhibitor, IRE1α pathway inhibitor, or TGF-β signaling activator, this study further revealed an essential role of intrinsic TGF-β signaling in regulating muscle cell to express inflammation-related molecules including H-2K b , H2-Eα, TLR3, and special myokines. TGF-β signaling prompted UPR IRE1α arm and restrained p38 MAPK activation in myofiber under inflammatory milieu. This study uncovers a previously unrecognized function of TGF-β signaling acting as an upstream factor controlling myofiber immune capacities in the inflamed state through the UPR–IRE1α–p38 MAPK pathway.

目的 探讨干扰素-γ(IFN-γ)诱导的炎症环境中,骨骼肌纤维内质网应激(ERS)与非折叠蛋白反应(UPR)的激活对肌纤维免疫行为的调控作用.方法 体外培养的C57BL/6小鼠原代成肌干细胞,经马血清分化成多核肌管后分成以下10组:1.对照组;2.IFN-γ组;3.衣霉素(TM)组;4.毒胡萝卜素(TG)组;5.IFN-γ+4-苯基丁酸(4-PBA)联合处理组;6.IFN-γ+TG+4-PBA联合处理组;7.IFN-γ+4μ8c联合处理组;8.IFN-γ+TG+4μ8c联合处理组;9.IFN-γ+GSK2606414联合处理组;10.1FN-γ+TG+GSK2606414联合处理组,并进行对应的处理.利用Real-time PCR检测相关肌细胞因子基因水平;免疫荧光观察UPR关键分子:真核翻译起始因子2α(eIF2α)、肌醇需要酶1α(IRE1α)、转录激活因子6(ATF6)在肌纤维内的表达;Western blotting检测肌细胞相关免疫分子和肌细胞因子及UPR关键分子;Luminex分析肌纤维内促炎症的肌细胞因子的蛋白水平.结果 IFN-γ诱导的炎症环境中,肌纤维H-2Kb、H2-Ea、Toll样受体3(TLR3)以及p-eIF2α、p-IRE1α表达上调;添加UPR抑制剂4-PBA的分组肌纤维H-2Kb、H2-Ea、TLR3以及肌细胞因子的表达较IFN-γ组下调,添加IRE1α特异性抑制剂4μ8c的分组上述分子表达较IFN-γ组亦下调,而添加蛋白激酶R样内质网激酶(PERK)特异性抑制剂GSK2606414的分组则无明显变化.结论 IFN-γ诱导的炎症环境中,UPR-IRE1α通路激活并抑制肌纤维免疫相关分子合成,从而进一步抑制肌纤维介导的免疫反应,有利于肌再生.

Background: CKLF like MARVEL transmembrane domain containing 6 (CMTM6) is an important programmed cell death 1 ligand 1 regulator (PD-L1). CMTM6 was reported as an important regulator of PD-L1 by promoting PD-L1 expression in tumor cells against T cells. However, the function of CMTM6 in cervical cancer is not well characterized. In addition, the role of CMTM6 in the induction of epithelial-mesenchymal transition (EMT) in the context of cervical cancer is unknown. Methods: In this study, we evaluated the role of CMTM6, including gene expression analysis, miRNA target regulation, and methylation characteristic, using multiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database. The expression of CMTM6 in cervical cancer tissues and non-cancerous adjacent tissues was assessed using immunohistochemistry. In vitro and in vivo function experiments were performed to explore the effects of CMTM6 on growth and metastasis of cervical cancer. Results: Human cervical cancer tissues showed higher expression of CMTM6 than the adjacent non-cancerous tissues. In vitro assays showed that CMTM6 promoted cervical cancer cell invasion, migration, proliferation, and epithelial-mesenchymal transition via activation of mitogen-activated protein kinase (MAPK) c-jun N-terminal kinase (JNK)/p38 signaling pathway. We identified transcription factors (TFs), miRNAs, and immune cells that may interact with CMTM6. Conclusion: These results indicate that CMTM6 is a potential therapeutic target in the context of cervical cancer.

Treatment of adult femoral neck fracture is still a great challenge faced by trauma orthopedists. As treatment effects can be infleunced by multiple factors, like age, gender and preoperative physical condition, they may vary with different treatment schemes. Classification of femoral neck fractures plays an important guiding role in choosing a proper treatment scheme and judging the prognosis. The current classic clinical classification systems for femoral neck fractures include Garden, AO/OTA and Pauwels classifications. Since the recent progress in science and technology has put more advanced technologies into clinic application, such as CT, MRI and Digital Subtraction Angiography (DSA), new ways of classification have appeared. However, each classification has its own shortcomings which need to be improved. This paper reviews the research progress in classification of adult femoral neck fractures and their treatment principles.

Transforming growth factor-β (TGF-β) is considered to be an important immune regulatory cytokine. However, it remains unknown whether and how the muscle fiber specific-TGF-β signaling is directly involved in intramuscular inflammatory regulation by affecting T cells. Here, we addressed these in a mouse tibialis anterior muscle Cardiotoxin injection-induced injury repair model in muscle creatine kinase (MCK)-Cre control or transgenic mice with TGF-β receptor II (TGF-βr2) being specifically deleted in muscle cells (SM TGF-βr2-/-). In control mice, TGF-β2 and TGF-βr2 were found significantly upregulated in muscle after the acute injury. In mutant mice, deficiency of TGF-β signaling in muscle cells caused more serious muscle inflammation, with the increased infiltration of macrophages and CD4+ T cells at the degeneration stage (D4) and the early stage of regeneration (D7) after myoinjury. Notably, the loss of TGF-β signaling in myofibers dramatically affected CD4+ T cell function and delayed T cells withdrawal at the later stage of muscle regeneration (D10 and D15), marked by the elevated Th17, but the impaired Tregs response. Furthermore, in vivo and in vitro, the intrinsic TGF-β signaling affected immune behaviors of muscle cells and directed CD4+ T cells differentiation by impairing IL-6 production and release. It suggests that local muscle inflammation can be inhibited potentially by directly activating the TGF-β signaling pathway in muscle cells to suppress Th17, but induce Tregs responses. Thus, according to the results of this study, we found a new idea for the control of local acute inflammation in skeletal muscle.NEW & NOTEWORTHY Myofiber mediates muscle inflammatory response through activating the intrinsic TGF-β signaling. The specific TGF-β signaling activation contributes to myofiber IL-6 production and directs muscle-specific Th17 and Treg cell responses.

Objective:To evaluate internal fixation via only the modified Stoppa approach in the treatment of central hip dislocation complicated with fracture of the posterior acetabular wall.Methods:A retrospective study was conducted in the 13 patients with central hip dislocation and fracture of the posterior acetabular wall who had been treated at Department of Orthopedic Trauma, Nanfang Hospital between February 2015 and February 2018. They were 10 men and 3 women, aged from 31 to 65 years (average, 46.7 years). All patients were treated with internal fixation via only the modified Stoppa approach. The reduction of double-column and posterior wall fractures was evaluated according to the X-ray Matta scoring system, as well as to the Wiberg central-edge (CE) angles between the vertical line of the center point of the femoral head and the lateral edge of the acetabulum and acetabular tolerance on the normal and affected sides immediately after operation; the hip function was evaluated by the modified Merle d'Aubigne and Postel scoring system at 12 months after operation.Results:All patients were followed up for 16 to 52 months (average, 25.6 months). In all of them, reduction and fixation of central hip dislocation and acetabular fracture was completed successfully, and indirect reduction of posterior wall fracture and acetabular tolerance were satisfactory. Operation time ranged from 130 to 270 min, averaging 155.5 min; intraoperative blood loss from 600 to 5,600 mL, averaging 1,150.5 mL; intraoperative infusion of concentrated red blood cells from 2 to 12 U, averaging 6 U. By the X-ray Matta scoring system immediately after operation, anatomical reduction was achieved in 4 posterior wall fractures and satisfactory reduction in 9 ones. There was no significant difference between the normal and affected sides in the CE angle (43.53°±3.46° for the affected side versus 43.19°±3.28° for the normal side) or in the acetabular tolerance (76.56%±15.50% for the affected side versus 75.32%±16.24% for the normal side) ( P>0.05). The modified Merle d'Aubigne and Postel scores at 12 months after operation ranged from 12 to 18 points, averaging 16.5 points; the hip function was assessed as excellent in 9 cases, as good in 3 and as fair in one. By the last follow-up, none of the 13 patients lost fracture reduction, and their internal fixation was firm with no loosening or breakage. Conclusion:In the treatment of central hip dislocation complicated with fracture of the posterior acetabular wall, internal fixation via only the modified Stoppa approach can lead to satisfactory fracture reduction, firm fixation, good hip joint tolerance, and fine clinical efficacy.

As the understanding of skeletal muscle inflammation is increasingly clarified, the role of Treg cells in the treatment of skeletal muscle diseases has attracted more attention in recent years. A consensus has been reached that the regulation of Treg cells is the key to completing the switch of inflammation and repair of skeletal muscle, whose presence directly determine the repairing quality of the injured skeletal muscle. However, the functioning process of Treg cells remains unreported, thereby making it necessary to summarize the current role of Treg cells in skeletal muscle. In this review, the characteristics, origins, and cellular kinetics of these Treg cells are firstly described; Then, the relationship between Treg cells and muscle satellite cells (MuSCs), conventional T cells (Tconv) is discussed (the former is involved in the entire repair and regeneration process, while the latter matters considerably in causing most skeletal muscle autoimmune diseases); Next, focus is placed on the control of Treg cells on the phenotypic switch of macrophages, which is the key to the switch of inflammation; Finally, factors regulating the functional process of Treg cells are analyzed, and a regulatory network centered on Treg cells is summarized. The present study summarizes the cell-mediated interactions in skeletal muscle repair over the past decade, and elucidates the central role of regulatory T cells in this process, so that other researchers can more quickly and comprehensively understand the development and direction of this very field. It is believed that the hereby proposed viewpoints and problems can provide fresh visions for the latecomers.

Femoral neck fracture in children is usually caused by high-energy trauma. This relatively rare injury characterized by skeletal immaturity is different from that in adult patients in proximal femoral anatomy and blood supply. Currently, a variety of fixation methods have been used for paediatric femoral neck fractures but their overall goal is anatomical reduction and stable fixation. Femoral neck fractures in children are usually associated with a high incidence of complications (e.g. femoral head necrosis, premature epiphyseal closure, coxa vara and nonunion) even after appropriate treatment. This review addresses the anatomic characteristics, treatment strategies and complications in the treatment of paediatric femoral neck fractures.

Objective To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle. Methods Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep‐tissue injury of the soft‐tissue defects. The skin flap and muscle flap were fanned out on the wound, and single‐ or two‐staged split‐thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post‐operationally. Complications at both recipient site and donor site were carefully recorded. Results The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post‐traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6–8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12–36 months post‐operational follow‐up. Conclusion The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.

Objective:To investigate the effect of transforming growth factor (TGF- β) signal in muscle fiber itself during inflammation/immunity response on intramuscular inflammation. Methods:Sixteen wild C57BL/6 mice (wild group) and sixteen mice with skeletal muscle-specific deficiency of T βRⅡ (knock-out group) between 4-8 weeks of age were selected for this study. Acute muscle injury in mice was induced by injection of myotoxin cardiotoxin (CTX) into gastrocnemius. The differences in intramuscular inflammation were compared between the wild and knock-out groups on 0, 4, 7 and 10 d after CTX injection by observing exudation of mononuclear phagocytes, macrophages, M1 type macrophages, CD4 +T cells and helpers T cells (Th1, 2&17). Two newborn C57BL/6 wild mice and 2 SM TGF- βr2-/- knock-out mice were selected to culture primary myoblasts in vitro which were divided into 2 groups: an interferon group subjected to interferon simulation and a control group subjected to addition of an equal amount of solvent. The differences in expression of IL-6, IL-10, MCP-1, MIP-1α, H-2K b, H2-Ea, Toll-like receptor (TLR)3 and TLR7 were compared between the interferon and control groups, as well as between the wild and knock-out groups. Results:On 4&7 d after CTX injection, the ratios of mononuclear/macrophage (75.73%±3.62%, 45.27%± 2.32%), macrophages (38.67%±2.76%, 24.87%±2.19%), M1 macrophages (43.21%±0.11%, 30.43%±2.19%), CD4 +T cells (20.13%±1.62%, 5.67%±0.32%) in the muscle tissue from the knock-out mice were significantly higher than those from the wild mice (58.52%±2.43%, 29.21%±2.45%; 20.63%±2.32%, 16.23%±1.25%; 24.98%±0.35%, 14.23%±1.69%; 10.70%±0.43%, 2.50%±0.45%), with a majority of Th1&Th17 ( P<0.05). In vitro results showed that the levels of IL-6, MCP-1, MIP-1α, H-2K b, H2-Ea and TLR3 were significantly upregulated in the interferon group compared with the control group and that such upregulation in the nock-out mice was more significant than in the wild mice ( P<0.05). Conclusions:Endogenous TGF- β signal activation plays a role in the functional recovery after muscle trauma, because it is involved in the regulation of immune behavior of muscle fibers, thus affecting intramuscular inflammation and muscle regeneration.