Silicon-induced biofilm improves peripheral nerve defect in rats mediated by VEGF/VEGFR2/ERK.

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.

[Application of antibiotic bone cement-coated plates internal fixation for primary treating Gustilo type â ¢B tibiofibular open fracture].

Objective: To explore the effectiveness of using antibiotic bone cement-coated plates internal fixation technology as a primary treatment for Gustilo type ⅢB tibiofibular open fractures. Methods: The clinical data of 24 patients with Gustilo type ⅢB 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 ⅢB 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.

Masquelet combined with free-flap technique versus the Ilizarov bone transport technique for severe composite tibial and soft-tissue defects.

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.

Irisin alleviates obesity-induced bone loss by inhibiting interleukin 6 expression via TLR4/MyD88/NF-κB axis in adipocytes.

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.

Fibromodulin facilitates the osteogenic effect of Masquelet's induced membrane by inhibiting the TGF-ß/SMAD signaling pathway.

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.

Overexpression of ETV2 in BMSCs promoted wound healing in cutaneous wound mice by triggering the differentiation of BMSCs into endothelial cells and modulating the transformation of M1 phenotype macrophages to M2 phenotype macrophages.

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.

Clinical effect of nice knot-assisted minimally invasive titanium elastic nail fixation to treat Robinson 2B midshaft clavicular fracture.

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).

Explore novel molecular mechanisms of FNDC5 in ischemia-reperfusion (I/R) injury by analyzing transcriptome changes in mouse model of skeletal muscle I/R injury with FNDC5 knockout.

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.

Suppression of Overactive Insulin-Like Growth Factor 1 Attenuates Trauma-Induced Heterotopic Ossification in Mice.

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.

A novel primary antibiotic cement-coated locking plate as a temporary fixation for the treatment of open tibial fracture.

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.

Synovial fluid exosome-derived miR-182-5p alleviates osteoarthritis by downregulating TNFAIP8 and promoting autophagy through LC3 signaling.

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.

A novel technique for treating simple transverse patellar fractures using cannulated screws: a cadaveric and clinical study.

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.

Comparison of osteogenic activity from different parts of induced membrane in the Masquelet technique.

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.

Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats.

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.

The significance of wrist immobilization for endoscopic carpal tunnel release.

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.

Analysis of the Risk Factors for Free Flap Necrosis in Soft Tissue Reconstruction of the Lower Limbs.

OBJECTIVE: Free flaps are widely used for the repair of soft tissue defects in the lower limbs, but there is still a specific rate of necrosis. Few clinical retrospective studies have analyzed the nontechnical risk factors for lower limb free flap necrosis. This study aimed to analyze the nontechnical causes of flap necrosis in lower limb soft tissue reconstruction in order to identify risk factors and improve the survival rate of free flaps. METHODS: Clinical data from 244 cases of soft tissue defects of the leg or foot that were repaired with a free flap from January 2011 to June 2020 were retrospectively analyzed. The flap results were divided into complete survival and necrosis groups. The patients' general information, smoking history, soft tissue defect site, Gustilo-Anderson classification, shock after injury, type and size of the flap, and time from injury to flap coverage were recorded. A logistic regression model was used to analyze the correlations between flap necrosis and possible risk factors. RESULTS: Of the 244 flaps, 32 suffered from partial or total necrosis, and 212 completely survived. Univariate analysis showed that age, smoking history, soft tissue defect site, and time from injury to flap coverage were significantly correlated with flap necrosis (p ≤ 0.2). Multivariate logistic regression analysis showed that moderate-to-severe smoking history (p < 0.001, odds ratio [OR] = 10.259, 95% confidence interval [CI] = 2.886-36.468), proximal leg defect (p = 0.006, OR = 7.095, 95% CI = 1.731-29.089), and time from injury to flap coverage >7 days (p = 0.003, OR = 12.351, 95% CI = 2.343-65.099) were statistically significant risk factors for flap necrosis (p < 0.05), and age was excluded (p = 0.666; p = 0.924). CONCLUSION: The risk of flap necrosis was significantly increased when the soft tissue defect was located in the proximal leg, the time from injury to flap coverage was >7 days, and the patient had a moderate-to-severe smoking history. These three risk factors have an increased influence on flap necrosis and have guiding significance in predicting flap prognosis.

A novel modified Winograd surgical tricks and tips with a "bird flap" for the treatment of ingrown toenails.

BACKGROUND: The Winograd technique is the most commonly used surgical treatment for ingrown toenails. We describe a novel modified approach, more effective and simpler to perform with a better cosmetic outcome. METHODS: We retrospectively included 45 and 39 patients with 67 and 58 ingrown toenails who underwent our modified Winograd technique and the Winograd technique, respectively, from July 2017 to June 2020, and obtained data after 3, 6, and 12 months of follow-up. RESULTS: No significant differences in the postoperative time taken to return to regular activities in the modified Winograd and traditional Winograd groups (p = 0.103) and regarding the recurrence in both groups (p = 0.055) were found. The extent of proximal germinal matrix exposure with the modified Winograd technique was significantly more clearly revealed than in the traditional Winograd method contextually (p < 0.05). The postoperative appearance satisfaction rate was significantly higher in the modified Winograd group than in the traditional Winograd group (p = 0.029). CONCLUSION: The modified Winograd technique is effective in treating ingrown toenails.

Treatment of inferior pole patella fracture using Krackow suturing combined with the suture bridge technique.

PURPOSE: To evaluate the feasibility and clinical effect of Krackow suturing combined with the suture bridge technique for the treatment of acute inferior pole patella fracture. METHODS: In this study, 18 patients with acute inferior pole patella fracture who received treatment using Krackow suturing combined with the suture bridge technique between January 2019 and March 2020 were retrospectively reviewed. There were 10 men and 8 women, with an average age of 50.1 years (range 24-69 years). X-ray examinations were performed to assess fracture healing and the Insall-Salvati index. The clinical effect was measured by the range of motion of the knee joint and the Böstman scale. RESULTS: Patients were followed up for 13-26 months, with an average follow-up period of 19.6 months. X-ray indicated that fracture union had occurred in all patients by 10.1 weeks after surgery on average (range 8-14 weeks). The mean Insall-Salvati index immediately after surgery and at the final follow-up was 0.98 ± 0.07 and 0.90 ± 0.22, respectively (P > 0.05). At the last follow-up, the mean flexion and extension ranges for the knee joint were 135.8° ± 8.8° and - 2.8° ± 3.9°, respectively, and the mean Böstman scale was 28.9 ± 1.1 points. Functional recovery was excellent in 17 patients and good in one patient, resulting in an overall good/excellent recovery rate of 100%. CONCLUSIONS: Our results indicated that Krackow suturing combined with the suture bridge technique can achieve stable fracture fixation, provides good clinical outcomes in the treatment of acute inferior pole patella fracture, and is worthy of clinical application.

Clinical effectiveness of early internal fixation combined with free flap technique in the treatment of Gustilo IIIB open forearm fracture.

INTRODUCTION: Gustilo IIIB open forearm fractures are severe injuries often associated with extensive bone and soft tissue injuries. The treatment of Gustilo IIIB open forearm fractures remains a challenging problem, with a high morbidity rate such as infection, nonunion, even amputation. External fixation is preferred for open lower limb fractures. However, there are significant differences between open bone injuries of the upper and lower extremity in terms of treatment plans. Use of internal fixation methods for open fractures is a controversial issue, as it requires early coverage of skin and soft tissue defects after radical debridement and irrigation. The optimal approach for open forearm fractures remains to be determined. The present study evaluated whether early internal fixation combined with free flap placement is effective for the treatment of Gustilo IIIB open forearm fracture. HYPOTHESIS: Early internal fixation combined with the free flap technique in the treatment of Gustilo IIIB open forearm fracture provides good consolidation results. MATERIAL AND METHODS: From January 2015 to January 2020, 20 patients with Gustilo IIIB open forearm fracture treated with early internal fixation combined with free skin flap placement were retrospectively analyzed. There were 9 males and 11 females, with an average age of 40 years. In all cases, the injuries were classified as Gustilo type IIIB. The area of the wounds ranged from 9×3cm to 27×10cm. Fist-stage plate fixation was adopted in 16 cases. Four patients presenting with major contamination received first-stage fixation with Kirschner wires and external fixation, and the second-stage surgery of surgical treatment included flap placement and internal fixation within 10 days. The rates of limb salvage and complications were recorded. The Anderson scoring system was utilized to assess limb function. RESULTS: Limb salvage was successful in all 20 cases. The average length of hospital was 19 days (range, 7-28 days). Four patients developed superficial infections. After debridement, the wounds were covered with skin grafts. No deep infections or osteomyelitis occurred. Three patients developed nonunion, and bone grafts achieved bone healing later. The donor skin flaps healed well, with partial pigmentation. No complete necrosis of the flaps occurred. Only the distal part of flaps became necrotic in two cases, which were then successfully treated by debridement and skin grafting. The average follow-up duration was 14.7 months (range, 8-24 months). According to the Anderson scoring system, 7 cases were graded as excellent, 6 cases as good, 5 cases as fair, and 2 cases as poor. CONCLUSION: For Gustilo IIIB type injuries, early and thorough debridement along with early internal fixation and skin flap coverage of the wound can achieve satisfactory clinical results, shorten the treatment cycle, and maximize limb function recovery. LEVEL OF EVIDENCE: IV, retrospective study without control group.

Clinical efficacy of the topical application of tranexamic acid in tendon release in the hand: A randomized controlled trial.

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 < 0.05). 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 < 0.05). 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 < 0.05). There was no significant difference in operation time and incidence of early postoperative complications between the 2 groups (p > 0.05). CONCLUSION: The topical application of tranexamic acid during hand tendon release can significantly reduce postoperative bleeding and improve surgical efficacy, which is worth promoting.