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OBJECTIVE: Clinical concerns exist regarding the quality of bony consolidation in the context of the induced membrane technique. This study evaluates the clinical process of bone grafting in the second stage of induced membrane bone union in patients with tibial bone defects to infer the possibility of non-union and establish a reliable and effective evaluation method combined with computed tomography (CT) to assess fracture healing. METHODS: Patients with tibial bone defects who underwent the induced membrane technique at our hospital between February 2017 and February 2020 were retrospectively analyzed. The Hounsfield unit (HU) values of the patients were evaluated at different times during the second stage of bone grafting. Bone healing at the boundary value of the 120 HU output threshold (-1024 HU-3071 HU) was directionally selected, and the changes in the growth volume of union (new bone volume [selected according to HU value]/bone defect volume) were compared with analyzing individual class bone union. Method 1 involved X-rays revealing that at least three of the four cortices were continuous and at least 2 mm thick, with the patient being pain free. For Method 2, new bone volume (selected according to HU value/bone defect volume) at the stage was compared with analyzing individual class healing. Receiver operating characteristic curve analysis was used for Methods 1 and 2. RESULTS: A total of 42 patients with a segmental bone defect with a mean age of 40.5 years (40.5 ± 8.3 years) were included. The relationship between bone graft volume and time variation was analyzed by single factor repeated variable analysis (F = 6.477, p = 0.016). Further, curve regression analysis showed that the change in bone graft volume over time presented a logarithmic curve pattern (Y = 0.563 + 0.086 × ln(X), Ra2 = 0.608, p = 0.041). ROC curve analysis showed that Method 2 is superior to Method 1 (AUC: 86.3% vs. 68.3%, p < 0.05). CONCLUSION: The induced membrane technique could be used to treat traumatic long bone defects, with fewer complications and a higher healing rate. The proposed imaging grading of HU (new bone volume/bone defect volume) can be used as a reference for the quality of bony consolidation with the induced membrane technique.
Subject(s)
Bone Transplantation , Fracture Healing , Tibial Fractures , Tomography, X-Ray Computed , Humans , Male , Female , Retrospective Studies , Fracture Healing/physiology , Adult , Bone Transplantation/methods , Tibial Fractures/surgery , Tibial Fractures/diagnostic imaging , Middle Aged , Young Adult , Aged , Fractures, Ununited/surgery , Fractures, Ununited/diagnostic imagingABSTRACT
In clinical flap practice, there are a lot of studies being done on how to promote the survival of distal random flap necrosis in the hypoxic and ischemic state. As a traditional Chinese medicine, dihydromyricetin (DHM) is crucial in preventing oxidative stress and apoptosis in a number of disorders. In this work, we examined the impact of DHM on the ability to survive of ischemia flaps and looked into its fundamental mechanism. Our results showed that DHM significantly increased the ischemic flaps' survival area, encouraged angiogenesis and blood flow, reduced oxidative stress and apoptosis, and stimulated KEAP1-Nrf2 (Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor) signaling pathways. Adeno-associated virus (AAV) upregulation of KEAP1 expression also negated the favorable effects of DHM on flap survival. By activating KEAP1-Nrf2 signaling pathways, DHM therapy promotes angiogenesis while reducing oxidative stress and apoptosis.
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The accumulation of excessive reactive oxygen species (ROS) and recurrent infections with drug-resistant bacteria pose significant challenges in diabetic wound infections, often leading to impediments in wound healing. Addressing this, there is a critical demand for novel strategies dedicated to treating and preventing diabetic wounds infected with drug-resistant bacteria. Herein, 2D tantalum carbide nanosheets (Ta4C3 NSs) have been synthesized through an efficient and straightforward approach, leading to the development of a new, effective nanoplatform endowed with notable photothermal properties, biosafety, and diverse ROS scavenging capabilities, alongside immunogenic attributes for diabetic wound treatment and prevention of recurrent drug-resistant bacterial infections. The Ta4C3 NSs exhibit remarkable photothermal performance, effectively eliminating methicillin-resistant Staphylococcus aureus (MRSA) and excessive ROS, thus promoting diabetic wound healing. Furthermore, Ta4C3 NSs enhance dendritic cell activation, further triggering T helper 1 (TH1)/TH2 immune responses, leading to pathogen-specific immune memory against recurrent MRSA infections. This nanoplatform, with its significant photothermal and immunomodulatory effects, holds vast potential in the treatment and prevention of drug-resistant bacterial infections in diabetic wounds.
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Background: Injury of peripheral nerve capable of regeneration with much poorer prognosis affects people's life quality. The recovery of nerve function after transplantation for peripheral nerve injury remain a worldwide problem. Silicon-induced biofilms as vascularized biological conduits can promote nerve regeneration by encapsulating autologous or allogeneic nerve graft.Objective: We proposed to explore the effect of silicon-induced biofilms on nerves regeneration and whether the VEGF/VEGFR2/ERK pathway was involved in the present study.Methods: Biofilms around the transplanted nerves in peripheral nerve injury rats were induced by silicon. Vascularization and proteins related to VEGF/VEGFR2/ERK were measured. Pathology and morphology of nerves were investigated after encapsulating the transplanted nerves by silicon-induced biofilms.Results: Our results indicated that the biofilms induced by silicon for 6 weeks showed the most intensive vascularization and the optimal effect on nerve regeneration. Moreover, silicon-induced biofilms for 4, 6 and 8 weeks could significantly secrete VEGF with the highest content at week 6 after induction. VEGFR2, VEGF, p-VEGFR2, ERK1, ERK2, p-ERK1 and p-ERK2 were expressed in the biofilms. p-VEGFR2, p-ERK1 and p-ERK2 expression were different at each time point and significantly increased at week 6 compared with that at week 4 or week 8 which was consistent with that 6 week of was the optimum time for biofilms induction to improve the nerve repair after peripheral nerve injury.Conclusion: Our results suggested that combination of silicon-induced autologous vascularized biofilm and autologous transplantation may promote the repair of rat sciatic nerve defect quickly through VEGF/VEGFR2/ERK pathway.
Subject(s)
Biofilms , Nerve Regeneration , Peripheral Nerve Injuries , Rats, Sprague-Dawley , Silicon , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2 , Animals , Vascular Endothelial Growth Factor Receptor-2/metabolism , Vascular Endothelial Growth Factor A/metabolism , Nerve Regeneration/drug effects , Nerve Regeneration/physiology , Silicon/pharmacology , Peripheral Nerve Injuries/metabolism , Biofilms/drug effects , Rats , Male , Disease Models, Animal , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Sciatic Nerve/drug effects , Sciatic Nerve/injuriesABSTRACT
INTRODUCTION: Obesity-induced bone loss affects the life quality of patients all over the world. Irisin, one of the myokines, plays an essential role in bone and fat metabolism. OBJECTIVE: Investigate the effects of irisin on bone metabolism via adipocytes in the bone marrow microenvironment. METHODS: In this study, we fed fibronectin type III domain-containing protein 5 (FNDC5, the precursor protein of irisin) knockout mice (FNDC5-/-) with a high-fat diet (HFD) for 10 weeks. The quality of bone mass was assessed by micro-CT analysis, histological staining, and dynamic bone formation. In vitro, the lipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assayed by Oil Red O staining, and the osteogenic differentiation was assayed by alkaline phosphatase staining. Meanwhile, the gene expression in the BMSC-differentiated adipocytes by RNA sequence and the involved pathway of irisin were determined by western blot and qRT-PCR were performed. RESULTS: The FNDC5-/- mice fed with a HFD showed an increased body weight, fat content of the bone marrow and bone, and a decreased bone formation compared with those with a standard diet (SD). In vitro, irisin inhibited the differentiation of BMSCs into adipocytes and alleviated the inhibition of osteogenesis derived from BMSCs by the adipocyte supernatant. RNA sequence and blocking experiment showed that irisin reduced the production of interleukin 6 (IL-6) in adipocytes through downregulating the TLR4/MyD88/NF-κB pathway. Immunofluorescence staining of bone marrow further confirmed an increased IL-6 expression in the FNDC5-/- mice fed with HFD compared with those fed with SD, which suffered serious bone loss. CONCLUSION: Irisin downregulates activation of the TLR4/MyD88/NF-κB pathway, thereby reducing IL-6 production in adipocytes to enhance the osteogenesis of BMSCs. Thus, the rescue of osteogenesis of BMSCs, initially inhibited by IL-6, is a potential therapeutic target to mitigate obesity-induced osteoporosis.
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BACKGROUND: The treatment of bone and soft-tissue defects after open fractures remains challenging. This study aimed to evaluate the clinical efficacy of the Masquelet technique combined with the free-flap technique (MFFT) versus the Ilizarov bone transport technique (IBTT) for the treatment of severe composite tibial and soft-tissue defects. METHODS: We retrospectively analysed the data of 65 patients with tibial and soft-tissue defects and Gustilo type IIIB/C open fractures treated at our hospital between April 2015 and December 2021. The patients were divided into two groups based on the treatment method: group A (n = 35) was treated with the MFFT and internal fixation, and group B (n = 30) was treated with the IBTT. RESULTS: The mean follow-up period was 28 months (range 13-133 months). Complete union of both soft-tissue and bone defects was achieved in all cases. The mean bone-union times were 6 months (range 3-12 months) in group A and 11 months (range 6-23 month) in group B, with a significant difference between the two groups (Z = -4.11, P = 0.001). The mean hospital stay was 28 days (range 14-67 d) in group A which was significantly longer than the mean stay of 18 days (range 10-43 d) in group B (Z = -2.608, P = 0.009). There were no significant differences in the infection rate between group A (17.1 %) and group B (26.7%) (χ2 = 0.867, P = 0.352). The Total Physical Health Scores were 81.51 ± 6.86 (range 67-90) in group A and 75.83±16.14 (range 44-98) in group B, with no significant difference between the two groups (t = 1.894, P = 0.063). The Total Mental Health Scores were significantly higher in group A (90.49 ± 6.37; range 78-98) than in group B (84.70 ± 13.72; range 60-98) (t = 2.232, P = 0.029). CONCLUSION: Compared with IBTT, MFFT is a better choice of treatment for open tibial and soft-tissue defects with Gustilo IIIB/C fractures. IBTT is the preferred option when the tibial bone defect is large or if the surgeon's expertise in microsurgery is limited.
Subject(s)
Fracture Fixation, Internal , Fractures, Open , Free Tissue Flaps , Ilizarov Technique , Soft Tissue Injuries , Tibial Fractures , Humans , Male , Soft Tissue Injuries/surgery , Female , Retrospective Studies , Fractures, Open/surgery , Adult , Middle Aged , Tibial Fractures/surgery , Treatment Outcome , Fracture Fixation, Internal/methods , Plastic Surgery Procedures/methods , Fracture Healing , Aged , Young Adult , Bone Transplantation/methods , Adolescent , Debridement/methodsABSTRACT
Objective: To explore the effectiveness of using antibiotic bone cement-coated plates internal fixation technology as a primary treatment for Gustilo type â ¢B tibiofibular open fractures. Methods: The clinical data of 24 patients with Gustilo type â ¢B tibiofibular open fractures who were admitted between January 2018 and December 2021 and met the selection criteria was retrospectively analyzed. Among them, there were 18 males and 6 females, aged from 25 to 65 years with an average age of 45.8 years. There were 3 cases of proximal tibial fracture, 6 cases of middle tibial fracture, 15 cases of distal tibial fracture, and 21 cases of fibular fracture. The time from injury to emergency surgery ranged from 3 to 12 hours, with an average of 5.3 hours. All patients had soft tissue defects ranging from 10 cm×5 cm to 32 cm×15 cm. The time from injury to skin flap transplantation for wound coverage ranged from 1 to 7 days, with an average of 4.1 days, and the size of skin flap ranged from 10 cm×5 cm to 33 cm×15 cm. Ten patients had bone defects with length of 2-12 cm (mean, 7.1 cm). After emergency debridement, the tibial fracture end was fixed with antibiotic bone cement-coated plates, and the bone defect area was filled with antibiotic bone cement. Within 7 days, the wound was covered with a free flap, and the bone cement was replaced while performing definitive internal fixation of the fracture. In 10 patients with bone defect, all the bone cement was removed and the bone defect area was grafted after 7-32 weeks (mean, 11.8 weeks). The flap survival, wound healing of the affected limb, complications, and bone healing were observed after operation, and the quality of life was evaluated according to the short-form 36 health survey scale (SF-36 scale) [including physical component summary (PCS) and mental component summary (MCS) scores] at 1 month, 6 months after operation, and at last follow-up. Results: All 24 patients were followed up 14-38 months (mean, 21.6 months). All the affected limbs were successfully salvaged and all the transplanted flaps survived. One case had scar hyperplasia in the flap donor site, and 1 case had hypoesthesia (grade S3) of the skin around the scar. There were 2 cases of infection in the recipient area of the leg, one of which was superficial infection after primary flap transplantation and healed after debridement, and the other was sinus formation after secondary bone grafting and was debrided again 3 months later and treated with Ilizarov osteotomy, and healed 8 months later. The bone healing time of the remaining 23 patients ranged from 4 to 9 months, with an average of 6.1 months. The scores of PCS were 44.4±6.5, 68.3±8.3, 80.4±6.9, and the scores of MCS were 59.2±8.2, 79.5±7.8, 90.0±6.6 at 1 month, 6 months after operation, and at last follow-up, respectively. The differences were significant between different time points ( P<0.05). Conclusion: Antibiotic bone cement-coated plates internal fixation can be used in the primary treatment of Gustilo type â ¢B tibiofibular open fractures, and has the advantages of reduce the risk of infection in fracture fixation, reducing complications, and accelerating the functional recovery of patients.
Subject(s)
Fractures, Open , Soft Tissue Injuries , Tibial Fractures , Male , Female , Humans , Middle Aged , Tibia/surgery , Bone Cements , Fractures, Open/surgery , Anti-Bacterial Agents , Cicatrix/surgery , Retrospective Studies , Quality of Life , Treatment Outcome , Tibial Fractures/surgery , Skin Transplantation , Fracture Fixation, Internal/adverse effects , Soft Tissue Injuries/surgeryABSTRACT
This study aimed to investigate the effects of E26-transformation-specific variant-2 (ETV2) overexpression on wound healing in a cutaneous wound (CW) model and clarify associated mechanisms. pLVX-ETV2 lentivirus expressing ETV2 was constructed and infected into BMSCs to generate ETV2-overexpressed BMSCs (BMSCs+pLVX+ETV2). The RT-PCR assay was applied to amplify ETV2, VE-cadherin, vWF, ARG-1, IL-6, iNOS, TGF-ß, IL-10, TNF-α. Western blot was used to determine expression of VE-cadherin and vWF. ETV2 induced differentiation of BMSCs into ECs by increasing CDH5/CD31, triggering tube-like structures, inducing Dil-Ac-LDL positive BMSCs. ETV2 overexpression increased the gene transcription and expression of VE-cadherin and vWF (P<0.01). Transcription of M1 phenotype specific iNOS gene was lower and transcription of M2 phenotype specific ARG-1 gene was higher in the RAW264.7+BMSCs+ETV2 group compared to the RAW264.7+BMSCs+pLVX group (P<0.01). ETV2 overexpression (RAW264.7+BMSCs+ETV2) downregulated IL-6 and TNF-α, and upregulated IL-10 and TGF-ß gene transcription compared to RAW264.7+BMSCs+pLVX group (P<0.01). ETV2-overexpressed BMSCs promoted wound healing in CW mice and triggered the migration of BMSCs to the wound region and macrophage activation. ETV2-overexpressed BMSCs promoted collagen fibers and blood vessel formation in the wound region of CW mice. In conclusion, this study revealed a novel biofunction of ETV2 molecule in the wound healing process. ETV2 overexpression in BMSCs promoted wound healing in CW mice by triggering BMSCs differentiation into endothelial cells and modulating the transformation of M1 pro-inflammatory and M2 anti-inflammatory macrophages in vitro and in vivo.
Subject(s)
Endothelial Cells , Tumor Necrosis Factor-alpha , Animals , Mice , Interleukin-10 , Interleukin-6 , Macrophages , Phenotype , Transforming Growth Factor beta , von Willebrand FactorABSTRACT
Masquelet's induced membrane (IM) technique is a promising treatment strategy for the repair of substantial bone defects. The formation of an IM around polymethylmethacrylate bone cement plays a crucial role in this technique. Several studies have indicated that IMs have bioactivity because they contain abundant blood vessels, a variety of cells, and biological factors. The bioactivity of an IM increases during the initial stages of formation, thereby facilitating bone regeneration and remodeling. Nevertheless, the precise mechanisms underlying the enhancement of IM bioactivity and the promotion of bone regeneration necessitate further investigation. In this study, we successfully developed a Masquelet IM model of critical femur defects in rats. By employing proteomics analysis and biological detection techniques, we identified fibromodulin (FMOD) as a pivotal factor contributing to angiogenesis and the enhanced bioactivity of the IM. A significant increase in angiogenesis and the expression of bioactive factors in the IM was also observed with the upregulation of FMOD expression. Furthermore, this effect is mediated through the inhibition of the transforming growth factor beta (TGF-ß)/SMAD signaling pathway. We also demonstrated that administering recombinant human FMOD enhanced osteogenesis in rat bone marrow mesenchymal stem cells and angiogenesis in human umbilical vein endothelial cells in vitro. Furthermore, the negative regulatory effect of the TGF-ß signaling pathway was verified. In conclusion, this study provides a novel theoretical basis for the application of IMs in bone-defect reconstruction and explores possible new mechanisms that may play an important role in promoting the bioactivity and osteogenic potential of IMs.
Subject(s)
Osteogenesis , Transforming Growth Factor beta , Rats , Humans , Animals , Fibromodulin , Human Umbilical Vein Endothelial Cells/metabolism , Transforming Growth Factor beta/metabolism , Signal TransductionABSTRACT
PURPOSE: To study the clinical effectiveness of the topical application of tranexamic acid in hand tendon release. METHODS: This was a randomized controlled trial conducted after receiving approval from the local ethics committee according to guidelines from the Helsinki Declaration. Eighty patients who underwent hand tendon release operation in our hospital from January 2021 to December 2022 were included and randomly divided into 2 groups. Patients in the tranexamic acid group (40 cases) received intraoperative topical application of 2 g of tranexamic acid after tendon release, while patients in the conventional group (40 cases) did not receive topical application of tranexamic acid during operation. The operation time, perioperative hemoglobin changes, total blood loss, incidence of early postoperative complications, and total active movement (TAM) before surgery and 6 months after surgery were compared between the 2 groups. The continuous variable which follows normal distribution expressed by mean ± SD and used t-test to compare between groups. Meanwhile, categorical variables were used by Chi-square test, and a p < 0.05 indicated that the differences were statistically significant. RESULTS: Both groups were followed up for 7 - 18 months, with a mean of 10.3 months. Postoperative decrease in hemoglobin was significantly less in the tranexamic acid group than in the conventional group (t = 7.611, p < 0.001). The total blood loss in the tranexamic acid group (74.33 ± 20.50) mL was less than that in the conventional group (83.05 ± 17.73) mL, and the difference was statistically significant (p < 0.05). Both groups showed improvement in thumb/finger flexion and extension range of motion after surgery, and the TAM improved compared with those before surgery, and the difference was statistically significant (p < 0.001). The TAM improved more significantly in the tranexamic acid group (87.68° ± 10.44°) than in the conventional group (80.47° ± 10.93°) at 6 months after surgery, with a statistically significant difference (t = 3.013, p < 0.001). There was no significant difference in operation time and incidence of early postoperative complications between the 2 groups (p = 0.798, 0.499, respectively). CONCLUSION: The topical application of tranexamic acid during hand tendon release can significantly reduce postoperative bleeding and improve surgical efficacy, which is worth promoting.
Subject(s)
Administration, Topical , Antifibrinolytic Agents , Tranexamic Acid , Humans , Tranexamic Acid/administration & dosage , Male , Female , Adult , Antifibrinolytic Agents/administration & dosage , Middle Aged , Blood Loss, Surgical/prevention & control , Treatment Outcome , Tendon Injuries/surgery , Hand/surgery , Operative Time , Postoperative Complications/prevention & controlABSTRACT
BACKGROUND: The treatment of completely displaced midshaft clavicle fractures is still controversial, especially Robinson 2B fractures. Titanium elastic nail (TEN) fixation is a good option for simple fractures, but no reports exist on its use in complex fractures. This study aimed to present a surgical method using the Nice knot-assisted TEN fixation to treat Robinson 2B midshaft clavicular fractures. METHODS: A retrospective analysis of 29 patients who underwent fixation with TEN and had a 1-year postoperative follow-up between 2016 and 2020 was performed. The fractures were classified as Robinson type 2B1 in 17 cases and type 2B2 in 12 cases. Length of the incision, postoperative shoulder function Disability of Arm Shoulder and Hand (DASH) score and Constant score, complications rate, and second surgical incision length were recorded. RESULTS: The length of the incision was 2-6 cm (average 3.7 cm). All incisions healed by first intention, and no infection or nerve injury occurred. The Constant score was 92-100 (average 96) and the DASH score was 0-6.2 (mean, 2.64). TEN bending and hypertrophic nonunion occurred in one case (3.4%) and implant irritation occurred in four cases (13.8%) Fixation implants were removed at 12-26 months (mean, 14.6 months) after surgery, and the length of the second incision was 1-2.5 cm (average 1.3 cm). CONCLUSIONS: Intramedullary fixation by TEN is approved as a suitable surgical technique in clavicular fracture treatment. Nice knot-assisted fixation provides multifragmentary fracture stabilization, contributing to good fracture healing. Surgeons should consider this technique in treating Robinson 2B midshaft clavicular fractures. TRIAL REGISTRATION: Retrospectively registered. This study was approved by the Ethics Committee of Wuxi Ninth People's Hospital (LW20220021).
Subject(s)
Fracture Fixation, Intramedullary , Fractures, Bone , Humans , Titanium , Clavicle/diagnostic imaging , Clavicle/surgery , Clavicle/injuries , Retrospective Studies , Treatment Outcome , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Fracture Healing/physiology , Fracture Fixation, Intramedullary/methods , Bone Plates , Fracture Fixation, Internal/adverse effectsABSTRACT
Heterotopic ossification (HO) is the ectopic bone formation in soft tissues. Aside from hereditary HO, traumatic HO is common after orthopedic surgery, combat-related injuries, severe burns, or neurologic injuries. Recently, mammalian target of rapamycin (mTOR) was demonstrated to be involved in the chondrogenic and osteogenic processes of HO formation. However, its upstream signaling mechanism remains unknown. The current study used an Achilles tendon puncture-induced HO model to show that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. Micro-computed tomography imaging showed that IGF-1 not only accelerated the rate of osteogenesis and increased ectopic bone volume but also induced spontaneous ectopic bone formation in undamaged Achilles tendons. Blocking IGF-1 activity with IGF-1 antibody or IGF-1 receptor inhibitor picropodophyllin significantly inhibited HO formation. Mechanistically, IGF-1/IGF-1 receptor activates phosphatidylinositol 3-kinase (PI3K)/Akt signaling to promote the phosphorylation of mTOR, resulting in the chondrogenic and osteogenic differentiation of tendon-derived stem cells into chondrocytes and osteoblasts in vitro and in vivo. Inhibitors of PI3K (LY294002) and mTOR (rapamycin) both suppressed the IGF-1-stimulated mTOR signal and mitigated the formation of ectopic bones significantly. In conclusion, these results indicate that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO.
Subject(s)
Ossification, Heterotopic , Osteogenesis , Animals , Mice , Insulin-Like Growth Factor I , Insulin-Like Peptides , Mammals , Ossification, Heterotopic/etiology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Receptor, IGF Type 1 , TOR Serine-Threonine Kinases , X-Ray MicrotomographyABSTRACT
BACKGROUND: Irisin, a myokine derived from proteolytic cleavage of the fibronectin type III domain-containing protein 5 (FNDC5) protein, is crucial in protecting tissues and organs from ischemia-reperfusion (I/R) injury. However, the underlying mechanism of its action remains elusive. In this study, we investigated the expression patterns of genes associated with FNDC5 knockout to gain insights into its molecular functions. METHODS: We employed a mouse model of skeletal muscle I/R injury with FNDC5 knockout to examine the transcriptional profiles using RNA sequencing. Differentially expressed genes (DEGs) were identified and subjected to further analyses, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction (PPI) network analysis, and miRNA-transcription factor network analysis. The bioinformatics findings were validated using qRT-PCR and Western blotting. RESULTS: Comparative analysis of skeletal muscle transcriptomes between wild-type (WT; C57BL/6), WT-I/R, FNDC5 knockout (KO), and KO-I/R mice highlighted the significance of FNDC5 in both physiological conditions and I/R injury. Through PPI network analysis, we identified seven key genes (Col6a2, Acta2, Col4a5, Fap, Enpep, Mmp11, and Fosl1), which facilitated the construction of a TF-hub genes-miRNA regulatory network. Additionally, our results suggested that the PI3K-Akt pathway is predominantly involved in FNDC5 deletion-mediated I/R injury in skeletal muscle. Animal studies revealed reduced FNDC5 expression in skeletal muscle following I/R injury, and the gastrocnemius muscle with FNDC5 knockout exhibited larger infarct size and more severe tissue damage after I/R. Moreover, Western blot analysis confirmed the upregulation of Col6a2, Enpep, and Mmp11 protein levels following I/R, particularly in the KO-I/R group. Furthermore, FNDC5 deletion inhibited the PI3K-Akt signaling pathway. CONCLUSION: This study demonstrates that FNDC5 deletion exacerbates skeletal muscle I/R injury, potentially involving the upregulation of Col6a2, Enpep, and Mmp11. Additionally, the findings suggest the involvement of the PI3K-Akt pathway in FNDC5 deletion-mediated skeletal muscle I/R injury, providing novel insights into the molecular mechanisms underlying FNDC5's role in this pathological process.
Subject(s)
MicroRNAs , Reperfusion Injury , Mice , Animals , Matrix Metalloproteinase 11/genetics , Matrix Metalloproteinase 11/metabolism , Transcriptome , Fibronectins/genetics , Fibronectins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Mice, Inbred C57BL , Muscle, Skeletal/metabolism , Transcription Factors/metabolism , Reperfusion Injury/metabolism , Reperfusion , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
Complex lower extremity trauma reconstruction remains a challenge. This study used an internal fixation composite structure of antibiotic cement plates as a temporary fixation to treat lower extremity Grade III open fractures; thus, reducing the treatment period and complications of external fixation. We aimed to assess the safety and efficacy of this technique in the initial surgery stage. Between January 2018 and March 2021, 20 patients with Gustilo grade IIIB/C open fractures received an antibiotic cement-coated locking plate as a temporary internal fixator during initial surgery. Thorough debridement and temporary internal fixation were performed with a 3.5-mm system antibiotic cement-coated locking plate. Ten patients required free bone fragment removal, followed by bone cement packing. The final stage involved internal fixation and wound repair with a free anterolateral thigh flap. Clinical and imaging results were retrospectively analysed. The repair time ranged 1-7 days. All flaps survived. Two patients experienced wound infection, and one developed severe bone infection 3 months after three-stage bone graft surgery. Autologous cancellous bone grafting was performed on 10 patients with bone defects 6 weeks after surgery. Bone union was universally achieved after 1 year. This method proved safe and effective, successfully repairing Grade III open fractures of the lower extremity 1-7 days post-treatment.
Subject(s)
Fractures, Open , Free Tissue Flaps , Tibial Fractures , Humans , Fractures, Open/surgery , Anti-Bacterial Agents/therapeutic use , Bone Cements/therapeutic use , Retrospective Studies , Treatment Outcome , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery , Tibial Fractures/drug therapy , Fracture Fixation, Internal/methods , Bone Plates , Fracture Fixation/methodsABSTRACT
BACKGROUND: Tension band wiring (TBW) has conventionally been used for the open reduction and internal fixation of the patella. However, it suffers from distinct disadvantages such as large incision, implant irritation, and need for subsequent implant removal. Here, we propose a novel technique using closed reduction and percutaneous fixation with three cannulated screws (TCS), which may be an alternative to this established conventional technique. Although some researchers have proposed alternative methods including closed reduction and cannulated screw fixation, with or without additional wires through the screws, and arthroscopic-assisted reduction and fixation, there are few studies that focus on the biomechanical stability of percutaneous fixation using only cannulated screws. Thus, the purpose of this study was to evaluate TCS versus TBW for simple transverse patellar fractures in cadaveric and patients' level, aiming to determine whether TCS show superiority over TBW in terms of biomechanical stability in a cadaveric study with benign clinical feasibility and outcomes in patients. METHODS: We conducted a cadaveric study with 15 knee specimens that had simple transverse patellar fractures. We used two fixation techniques: TBW (group A, n = 6) and TCS (group B, n = 9). We applied sinusoidal forces (25 N-125 N) at 1/5 Hz and 90° knee flexion to simulate knee movement. We compared the displacements at the fracture site between the two groups. We also used the same technique in a total of 23 patients and followed up them for at least 1 year. RESULTS: TCS demonstrated favourable biomechanical stability in the cadaveric study. The technique also performed excellently in terms of postoperative pain, knee function recovery, and complication rates during the follow-up period. CONCLUSIONS: The technique provides a surgical treatment option with small incisions, minimal soft tissue irritation, and possibly lower removal rate of bothersome material.
Subject(s)
Fractures, Bone , Knee Injuries , Humans , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Bone Screws , Bone Wires , Patella/surgery , Knee Injuries/surgery , CadaverABSTRACT
OBJECTIVE: To investigate the role of exosomal miRNAs from synovial fluid (SF) in osteoarthritis (OA) patients and investigate the underlying molecular mechanism. METHODS: Degenerated knee tissues were collected from male and female OA patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the differences in the expression of inflammatory indicators, including TNF-α, IL-6, and IL-10, between the degenerative and injury groups. Exosomes were isolated from SF using the Exoquick kit, and a microarray was used to identify differentially expressed miRNAs (DEmiRNAs), which were analyzed using bioinformatics. The predicted relationship between DEmiRNAs and target genes was verified using a luciferase reporter gene assay. CCK-8 and transwell assays were used to assess cell viability and migration. Immunofluorescence and TUNEL assay were used to detect cell autophagy and apoptosis. The interaction between proteins was detected by immunoprecipitation and verified by Mab rescue assay. RESULTS: The relative expression of TNF-α/IL6 was significantly higher in the degeneration group than in the injury group. The OA degeneration group released significantly more and smaller exosomes than the injury group. The expression of miR-182-5p was markedly reduced in OA patients and had a higher correlation with inflammatory indicators. Tumor necrosis factor α-induced protein 8 (TNFAIP8) was a target of miR-182-5p, and its overexpression promoted chondrocyte proliferation, migration, and invasion and enhanced the wound healing efficiency. We also found a direct interaction of TNFAIP8 with autophagy-related gene 3 (ATG3). TNFAIP8 triggered ATG3 LC3-mediated autophagy. CONCLUSION: The downregulation of exosomal miR-182-5p inhibits OA degeneration by targeting TNFAIP8 via the ATG/LC3 pathway.
Subject(s)
Exosomes , MicroRNAs , Osteoarthritis , Female , Humans , Male , Apoptosis/genetics , Autophagy/genetics , Chondrocytes/metabolism , Exosomes/metabolism , MicroRNAs/metabolism , Osteoarthritis/metabolism , Synovial Fluid/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: The Masquelet technique is widely used to treat long-bone segmental defects because of its high success rate and low surgical difficulty. However, the cause of the uneven growth of bone grafts following this procedure remains unclear. METHODS: Rats were randomly divided into four groups for analysis 2-, 4-, 6- and 8-weeks postoperatively and underwent a uniform surgical procedure to construct a 10 mm bone defect in the right posterior branch of the femur. Induced membrane specimens were harvested at the appropriate time points and divided into segments according to their location. Bone growth activity was assessed by immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction. RESULTS: Mature blood vessels were more densely distributed at the proximal end of the bone defect than at other locations at all time points. The number of blood vessels on the same side of the longitudinal axis of the femur also varied depending on location. The difference between the proximal-anterior and distal-anterior regions within the induced membranes was most pronounced at 6 weeks postoperatively and decreased by 8 weeks postoperatively. The differences between the proximal-posterior and distal-posterior regions within the induced membranes were more pronounced. The expression of the growth factors bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor A(VEGFA), and transforming growth factor-ß1(TGF-ß1) in the proximal-posterior regions of the bone defect was almost always higher than that in other regions at the same time point. The expression of BMP-2 in the posterior regions of the bone defect was always higher than that in the anterior regions at the same end of the femoral longitudinal axis. CONCLUSION: The number and maturation of vessels in the proximal region of the induced membrane at the bone defect site were higher than those in the distal region, and the expression of growth factors was higher, with the highest induced membrane activity in the proximal-posterior regions of the bone defect. Therefore, there was inhomogeneity in induced membrane activity.
Subject(s)
Osteogenesis , Vascular Endothelial Growth Factor A , Rats , Animals , Vascular Endothelial Growth Factor A/metabolism , Bone and Bones , Femur/surgery , Femur/metabolismABSTRACT
Roxadustat (FG-4592) is a specific hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor. We investigated the effects of FG-4592 pretreatment on survival and second choke vessels of multi-territory perforator flaps in rats. In total, 72 rats were divided into two groups (n = 36 each): the experimental (FG-4592) group and the control group. FG-4592 was administered orally as a single dose of 60 mg/kg every other day; the first drug solution was administered to the animals 7 days before the surgical procedure. On postoperative day 7, the surviving flap area was calculated. At 12 h post-surgery, in the second choke zone in the flaps, macrovascular hinges were compared by angiography and imaging, and microvascular changes were assessed by histology. Laser Doppler imaging was used to evaluate flap perfusion at the second choke zone at 12 h and 7 days after surgery. At 7 days after surgery, the flap survival area and perfusion were significantly greater in rats given FG-4592 compared with controls. At 12 h after surgery, the diameter of macrovascular and microvascular vessels, nitric oxide content, perfusion, and the protein levels of HIF-1α and inducible nitric oxide synthase were also significantly greater in FG-4592-treated rats than controls. In conclusion, pretreatment with roxadustat may improve initial flap survival and dilate the second choke zone vessels in a multi-territory perforator flap.
ABSTRACT
Background: Over the years, endoscopic carpal tunnel release (ECTR) has gained significant interest as an alternative to surgery. However, no consensus has been reached on the necessity of postoperative wrist immobilization. This study aims to compare the outcomes of wrist immobilization for a period of 2 weeks to immediate wrist mobilization after ECTR. Methods: A total of 24 patients with idiopathic carpal tunnel syndrome undergoing dual-portal ECTR from May 2020 to Feb 2022 were enrolled and randomly divided into two groups postoperatively. In one group, patients wore a wrist splint for 2 weeks. In another group, wrist mobilization was allowed immediately after surgery. The two-point discrimination test (2PD test); the Semmes-Weinstein monofilament test (SWM test); the occurrence of pillar pain, digital and wrist range of motion (ROM); grip and pinch strength; the visual analog score (VAS), the Boston Carpal Tunnel Questionnaire (BCTQ) score; the Disabilities of the Arm, Shoulder, and Hand (DASH) score; and complications were evaluated at 2 weeks and 1, 2, 3, and 6 months after the surgery. Results: All 24 subjects finished this study with no dropouts. During the early follow-up, patients with wrist immobilization demonstrated lower VAS scores, lower occurrence of pillar pain, and higher grip and pinch strength compared with the immediate mobilization group. No significant difference was obtained between these two groups in terms of the 2PD test, the SWM test, digital and wrist ROM, BCTQ, and the DASH score. In total, two patients without splints reported transient scar discomfort. No one complained of neurapraxia, injury of the flexor tendon, median nerve, and major artery. At the final follow-up, no significant difference was found in any parameters between both groups. The local scar discomfort mentioned above disappeared and left no serious sequela. Conclusion: Wrist immobilization during the early postoperative period demonstrated significant pain alleviation along with stronger grip and pinch strength. However, wrist immobilization yielded no obvious superiority regarding clinical outcomes at the final follow-up.