Objective:To explore the applications of ultrasound guidance in the closed reduction of distal radius metaphysis fracture (DRM) in children. Methods:A retrospective analysis was conducted on 74 children of completely displaced DRM, who were admitted between October 2019 and March 2024 and met the selective criteria. All cases were made an attempt of closed reduction and plaster cast fixation. If closed reduction failed, the patient was readmitted for reduction under anesthesia and Kirschner wires fixation. The ultrasound group consisted of 25 cases reduced under ultrasound guidance. The fluoroscopy group consisted of 22 cases reduced under fluoroscopy guidance. The control group consisted of 27 cases reduced without any imaging device. There was no significant difference in the baseline data among the three groups ( P>0.05), including age, gender, involved side, cause of injury, interval from injury to reduction, and proportion of concomitant distal ulnar fracture. The reduced time, fluoroscopy frequency, and complication of the three groups were recorded, as well as the successful reduction rate, the re-displacement rate, and the ultimate reduction rate. At last follow-up, modified Green-O'Brien score was used to assess the recovery of the function in involved wrists. Results:The successful reduction rates and ultimate reduction rates were significantly higher in ultrasound group and fluoroscopy group than in control group ( P<0.05). But no significant difference was found between ultrasound group and fluoroscopy group ( P>0.05). The re-displacement rates and reduced time showed no significant difference among the three groups ( P>0.05). The fluoroscopy frequency was significantly higher in fluoroscopy group than in ultrasound group and control group ( P<0.05). But no difference was found between ultrasound group and control group ( P>0.05). All patients were followed up 13-16 months (mean, 14 months). All fractures healed within 4 to 6 weeks after the final reduction/operation. At last follow-up, the functions of involved wrists were all evaluated as excellent according to modified Green-O'Brien score in the three groups. Conclusion:Satisfactory outcomes of DRM in children treated with closed reduction under ultrasound guidance and plaster cast fixation can be achieved with radiation-free advantage compared with reduction under fluoroscopy and a higher successful reduction rate compared with reduction without imaging device.

Treatment of open tibial fractures remains a major challenge in clinical settings. The conventional method of temporary fracture fixation is external fixation. In this study, we aimed to evaluate the clinical efficacy and safety of antibiotic-loaded cement-coated plate (ACLP) internal fixation in the emergency management of patients with severe open tibial fractures undergoing delayed flap coverage. We hypothesized that emergency ACLP internal fixation can reduce the incidence of deep infection. This retrospective study involved 73 patients with Gustilo type IIIB tibial fractures treated at our hospital between June 2016 and December 2023. Patients were divided into two groups based on the method of emergency temporary fixation: Group A (n = 34) received ACLP internal fixation and Group B (n = 39) received external fixation. Definitive internal fixation and wound repair were performed 2–7 d later. Bone union and soft-tissue repair were achieved in both groups. The incidence of deep infection was 11.76

This study evaluated the effectiveness of a combination technique for managing severe composite tibial and soft-tissue defects, without requiring complex soft-tissue procedures. A retrospective analysis was conducted on 33 patients with tibial and soft-tissue defects and Gustilo type IIIB open fractures treated between April 2017 and December 2023. The management protocol for all patients consisted of two stages. The first stage involved thorough debridement in the emergency department, removal of all free tibial bone fragments, and fixation with an external frame. The second stage involved Ilizarov bone transport, utilizing chess-shaped polymethyl methacrylate (PMMA) cement (thickness: approximately 1 cm) to fill the tibial bone defect. The PMMA was gradually removed until bone union was achieved. Bone union and soft-tissue healing were achieved in all patients, without the need for additional flap transplantation. The mean bone-union time was 7.5 ± 1.4 months, and the mean soft-tissue healing duration was 70.9 ± 24.1 days. The mean traction period was 105.3 ± 48.2 days, the mean external fixation time was 444.0 ± 137.2 days, and the mean external fixation index was 58.2 ± 23.1 days/cm. Using the Lower Extremity Functional Scale (LEFS) and 36-Item Short-Form Health Survey to evaluate functional scoring, the mean LEFS, physical health component, and mental health component scores were 59.8±13.9, 70.5±17.7, and 77.8±20.1, respectively. According to Paley's classification of complications, there were 14 problems, 6 obstacles, and no sequelae. The chess-shaped PMMA-Ilizarov technique effectively treated composite tibial and soft-tissue defects. This approach facilitated the gradual regeneration and repair of bone and soft-tissue defects, avoided the need for additional skin flap transplantation, and achieved satisfactory clinical results.

Background:Skeletal muscle ischaemia-reperfusion (I/R) injury involves complex redox dysregulation with limited treatments. Although ferroptosis contributes to other organ I/R injuries, its role and regulation in skeletal muscle remain unclear. This study aimed to investigate the role and regulatory mechanism of ferroptosis in skeletal muscle I/R injury, specifically focusing on whether hypoxia-inducible factor 1 alpha (HIF1A) transcriptionally activates cyclin-dependent kinase inhibitor 1a (CDKN1A/p21) to drive this process. Methods:We employed integrative transcriptomics and Cleavage Under Targets and Tagmentation (CUT&Tag, a chromatin mapping technique) sequencing in murine I/R models. Genetic inhibition (Hif1a siRNA) and pharmacological inhibition (LW6) were utilized in vitro and in vivo. Cdkn1a overexpression was performed for rescue experiments. Ferroptosis was assessed by examining mitochondrial ultrastructure, quantifying lipid peroxidation, and evaluating the expression of key proteins: glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), and prostaglandin-endoperoxide synthase 2 (PTGS2). Clinical relevance was evaluated by co-expression analysis of HIF1A and CDKN1A in human I/R-affected muscle biopsies. Results:HIF1A directly bound to the Cdkn1a promoter during nuclear translocation, upregulating its expression. Both HIF1A inhibition (genetic or pharmacological) significantly attenuated ferroptosis, evidenced by preserved mitochondria, reduced lipid peroxidation, and normalized ferroptosis-related protein levels. Crucially, Cdkn1a overexpression reversed the anti-ferroptotic effects of Hif1a knockdown, confirming CDKN1A as a key downstream effector. Strong positive co-expression of HIF1A and CDKN1A was observed in human I/R biopsies (Spearman's r = 0.543, p = 0.006). Mechanistically, the HIF1A-CDKN1A axis exacerbated redox stress via glutathione depletion and intracellular free iron accumulation. Conclusion:Our findings establish HIF1A as a context-dependent ferroptosis amplifier in skeletal muscle I/R injury, acting through direct transcriptional activation of Cdkn1a. This HIF1A-CDKN1A axis drives ferroptosis by disrupting redox homeostasis. Targeting HIF1A and CDKN1A within this pathway provides two complementary molecular entry points for mitigating skeletal muscle I/R injury. The Translational Potential of this Article:Targeting the HIF1A-CDKN1A axis offers a promising therapeutic approach to reduce skeletal muscle damage and improve clinical outcomes after ischaemia-reperfusion injury.

Osteosarcoma (OS)-induced bone abnormalities present a considerable clinical challenge due to elevated chances of recurrence and compromised repair, which significantly jeopardize patient survival. Contemporary bioactive glasses (BGs), notwithstanding their osteogenic potential, exhibit restricted anticancer efficacy. Therefore, It is essential to enhance the tumor-killing efficacy of BGs for usage as a filler in tumor-induced bone defects. Here, a copper (Cu)-doped 13-93BG (13-93BG-Cu) was synthesized and subsequently combined with chitosan to form the 13-93BG-Cu system. The rapid release of Cu ions (Cu2 +) during the initial stages of this system enhances the killing of tumor cells by cuproptosis, as intracellular Cu2+ accumulation triggers the oxidative stress response within mitochondria, hence achieving anti-OS therapy. Subsequently, the sustained low-level release of Cu2+ and bioactive ions collaboratively influences the activation and function of macrophage and stem cells, promoting bone defect healing. This study introduces a dual-action BG that simultaneously neutralizes the acidic tumor microenvironment and promotes cuproptosis, effectively preventing recurrence while facilitating bone healing via Cu2+ gradient release.

Heterotopic ossification (HO) is a debilitating disorder characterized by pathological ectopic bone formation with limited effective treatments. Endothelial-mesenchymal transition (EndMT) has been implicated in traumatic HO pathogenesis, but the upstream signaling cascades governing this cellular reprogramming event are poorly defined. Here, we integrated reanalyzed single‑cell RNA sequencing transcriptomic profiles with a series of in vitro and in vivo functional assays to explore the potential molecular mechanism linking EndMT to traumatic HO. Single-cell transcriptomic profiling suggests that TGF‑β2 secreted by mesenchymal cell subsets may elicit endothelial phenotypic alterations reminiscent of EndMT via the canonical TGF‑β2-Smad2/3 signaling cascade. In line with this, sustained activation of the TGF‑β2-Smad2/3 signaling cascade was detected across the development of traumatic HO. These phenotypic alterations may confer chondro‑osteogenic potential on vascular endothelial cells and promote ectopic bone formation. Both genetic ablation and antibody‑mediated neutralization of TGF‑β2 mitigated pathological ossification, likely by blunting EndMT progression. Furthermore, SIS3, a small-molecule compound preferentially suppresses Smad3 phosphorylation, substantially attenuated TGF‑β2‑induced EndMT-like phenotypic shifts and reduced ectopic bone formation under both local intratendinous and systemic administration in mice. Collectively, our study proposes a potential TGF‑β2-Smad2/3 signaling axis linked to EndMT-like phenotypic plasticity during traumatic HO, and provides preliminary mechanistic basis for further preclinical evaluation of Smad3-targeted intervention for HO prevention.

The relationship between the local microenvironment and the pro-regenerative capacity of silicone-induced vascularized biological membranes remains poorly characterized. This study aimed to define the spatial heterogeneity of these intramuscular membranes and elucidate the underlying mechanisms by which they support peripheral nerve repair. In a rat sciatic nerve defect model, silicone rods were implanted at three distinct sites: within the nerve defect, adjacent to the nerve, and deep within muscle tissue distant from the nerve. Membranes were analyzed at multiple time points using gross observation, histology, Western blotting, and immunohistochemistry. Results revealed a bilayered membrane structure, featuring an inner synovial-like lining and a vascularized outer layer rich in collagen and fibroblasts. Membrane thickness increased over time, plateauing by 8 weeks. A distinct spatial gradient was observed: at 6 weeks, vascularization (assessed by CD31 staining) and the content of key neurotrophic factors (NGF, GDNF, VEGF) were highest at the nerve defect site and lowest in distant muscle. Co-localization of VEGF with the fibroblast marker Vimentin suggested fibroblasts as a potential cellular source of VEGF. In complementary in vitro studies, co-culture with the membrane protected Schwann cells under hypoxic stress by inhibiting apoptosis, enhancing migration, and reducing oxidative damage while preserving mitochondrial function. Collectively, these findings demonstrate that the silicone-induced biological membrane is a heterogeneous, bioactive structure. Its pro-regenerative potential, which is maximal in proximity to the nerve stump, is likely mediated by fibroblast-derived trophic factors including VEGF. Moreover, the membrane directly confers multifaceted cytoprotection to Schwann cells, highlighting its potential as a supportive pro-regenerative niche for peripheral nerve regeneration.

OBJECTIVE:Current classifications inadequately address distal clavicle fracture instability due to their coronal plane focus, neglecting multiplanar displacement and underestimation of complexity on routine radiographs. This study aimed to bridge this gap by employing three-dimensional (3D) fracture mapping to characterize injury patterns, offering mechanistic insights to optimize surgical strategies. METHODS:A retrospective analysis was conducted on 81 patients diagnosed with acute distal clavicle fractures at Wuxi Ninth People's Hospital between 2019 and 2022. Axial and sagittal CT planes were utilized to demonstrate fracture line alignment. Manual simulated repositioning was performed for all fracture lines, which were subsequently graphically superimposed onto a standard template of the intact distal clavicle. A 3D map was generated and subsequently transformed into a heatmap. The classification of distal clavicle fractures was determined based on the updated and modified Neer classification. Two points were designated at the distal end of the fracture block and at the repositioned counterpart to assess the three-dimensional spatial position, including shortening along the x-axis, horizontal displacement along the y-axis, vertical displacement along the z-axis, as well as the displacement angles in the three planes, thereby quantifying the displacement of each distal clavicle fracture. RESULTS:This study included 81 cases of distal clavicle fractures (43 cases on the left side and 38 cases on the right side). The distribution included 8 cases (9.88%) of Neer I, 5 cases (6.17%) of Neer IIA, 31 cases (38.27%) of Neer IIB, 11 cases (13.58%) of Neer IIC, 14 cases (17.28%) of Neer III, and 12 cases (14.81%) of Neer V. Fracture mapping revealed that the fracture lines were predominantly located in the distal one-third of the distal clavicle, with the highest concentration at the acromion end. The majority of displaced distal clavicle fractures exhibit multidirectional displacement, mainly posterior, superior, and shortening, along with angulation in the corresponding directions. CONCLUSIONS:Most displaced distal clavicle fractures involve multiple displacements and angulations, necessitating three-dimensional analysis during fracture reduction. A comprehensive 3D assessment of displacement patterns is essential for evaluating stability and guiding treatment. Fracture line analysis further enhances classification accuracy and informs imaging protocols and fixation strategies tailored to specific fracture types.

Herein, we show a molecular pathway driven by an evolutionarily conserved microRNA (miRNA) in sensory neurons to control neuropathic pain. By employing high-throughput sequencing analysis, we find that miRNA-323-3p (miR-323-3p) exhibits the most significant upregulation in injured trigeminal ganglia (TGs). Local inhibition of miR-323-3p in injured TGs suppresses established trigeminal neuropathic pain but has no effect on inflammatory pain. Mechanistically, nerve injury upregulates the protein expression of protein arginine methyltransferase 2 (PRMT2), which promotes asymmetric dimethylation of H3R8, thereby facilitating the binding of the transcription factor forkhead box A2 (FOXA2) to the miR-323-3p promoter and resulting in the upregulation of miR-323-3p expression. Furthermore, the increased miR-323-3p expression induces significant reductions in Kv2.1 protein expression and channel currents, resulting in TG neuronal hyperexcitability. Conversely, the downregulation of miR-323-3p in injured TGs restores the decreased Kv2.1 expression and attenuates nerve-injury-induced mechanical hypersensitivity. The PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons may offer therapeutic targets in neuropathic pain management.

PURPOSE:The disability and rehabilitation challenges resulting from severe upper extremity trauma impose significant burdens on individuals, families, and society, profoundly impacting patients' quality of life. This study aims to elucidate the information needs of patients undergoing limb salvage following severe upper extremity trauma through qualitative interviews, providing a foundation for the development of intervention strategies and mobile information support solutions. METHODS:Data were collected using a semi-structured interview framework based on Roy's Adaptation Model. Twenty-three patients who underwent limb salvage for severe upper extremity trauma were recruited. The interview transcripts were analyzed through a phenomenological approach. RESULTS:The analysis, informed by the accessibility of medical knowledge, identified three themes and 9 subthemes: (1) Information needs for surgical option selection; (2) Information needs for rehabilitation nursing; (3) Psychosocial support needs. CONCLUSION:Healthcare providers must pay attention to patients' post-operative information needs, recognize the importance of multi-domain information support, and provide tailored information solutions and interventions to enhance patients' well-being, facilitate post-traumatic growth, and restore social function.

BACKGROUND:Research on open tibiofibular fractures is limited. We compared clinical outcomes of Gustilo - Anderson type IIIB/C open tibial fractures using orthopedic and orthoplastic approaches, and identified poor prognosis predictors. MATERIALS AND METHODS:The clinical data of 746 patients with Gustilo - Anderson type IIIB/C open tibial fractures (420 and 326 treated using the orthopedic and orthoplastic approach, respectively) were retrospectively analyzed. We evaluated infection rates, nonunion incidence, arthritis incidence, number of surgeries, fracture healing time, amputation rate, wound closure duration, and Lower Extremity Functional Scale (LEFS) score, and identified risk factors affecting prognosis. RESULTS:Significant differences in infection rates (deep infection, 8.0% vs. 29%; superficial infection, 8.0% vs. 41%; all P <0.001), nonunion incidence (11% vs. 2.5%, P <0.001), arthritis incidence (27% vs. 2.1%, P < 0.001), number of surgeries (4.6 ± 1.07 vs. 10.7 ± 3.33, P < 0.001), and wound coverage time (11.27 ± 5.14 vs. 3.98 ± 1.98, P < 0.001) were observed between the groups. LEFS scores from 3 to 24 months after injury were higher in the orthoplastic group. No difference in fracture healing time was observed (7.0 ± 1.99 vs. 7.0 ± 1.98, P = 0.987). The orthoplastic group required a lower amount of bone graft when using intramedullary nail fixation (6.8 ± 1.42 vs. 19.0 ± 2.88, P < 0.001). Smoking (odds ratio [OR], 0.24 for nonunion; 95% confidence interval [CI], 2.29-5.34; P = 0.008 and OR, 0.26 for deep infection; 95% CI, 0.10-0.71; P = 0.009), bone cement block formation (OR, 1.54; 95% CI, 2.06-4.73; P = 0.007), and local antibiotic use (OR, 4.89; 95% CI, 1.93-12.37; P < 0.001) were predictors of poor prognosis. CONCLUSION:The orthoplastic approach offers advantages in the treatment of Gustilo - Anderson type IIIB/C open tibial fractures. Smoking should be avoided, bone cement block molding should be actively adopted, and systemic and local antibiotics should be administered as early as possible. The Flap and Open Reduction Internal Fixation and Masquelet technique reduces the amount of bone graft without increasing deep infection risk.

Background:Open fractures are critical injuries that require prompt and accurate diagnosis to optimize treatment outcomes. Traditional methods often rely on manual interpretation of radiological images, which can be prone to human error. With advancements in deep learning, there is a significant opportunity to enhance the precision of fracture classification through automated systems. Methods:Based on this, we developed a deep learning image processing model for the binary classification of tibiofibula open and closed fractures. By incorporating hybrid convolution with multi-scale convolutional kernels, we enhanced the model's feature extraction capabilities. To further optimize the feature selection process for orthopedic images, we integrated a channel attention mechanism, improving feature extraction without significantly increasing computational costs. Results:The results of the comparative experiments with other models show that our model's accuracy (ACC) surpasses that of the state-of-the-art classification models by 4.71%. Additionally, the F1 score of our model demonstrates a 4.77% improvement in precision. Moreover, the results of the ablation experiments indicate that each component of the constructed model effectively enhances performance. Conclusion:The findings of this study suggest that the proposed deep learning model significantly enhances the detection accuracy of open fractures. By integrating advanced feature extraction techniques and leveraging pre-trained models, our approach offers a promising tool for clinical application in orthopedic imaging, potentially leading to improved patient outcomes through more accurate diagnoses. Future work will focus on expanding the model's capabilities to include other fracture types and real-world clinical scenarios.

BACKGROUND:The paratenon has been shown to promote Achilles tendon healing, but the evidence supporting the role of paratenon protection technique in Achilles tendon repair is sparse. We retrospectively assessed the results of a paratenon-sparing repair technique vs an open giftbox repair of Achilles tendon ruptures. METHODS:Patients with Achilles tendon rupture who underwent surgical treatment at our hospital between January 2015 and August 2021 were retrospectively reviewed. Among them, 61 patients underwent surgical repair using the minimally invasive paratenon protection technique (MI group) and 67 patients using the open repair giftbox technique (OR group). The postoperative rehabilitation protocol was identical in both groups. The operation time, complication rate, length and cross-sectional area (CSA) of Achilles tendon, shear wave elastography (SWE), CSA of the calf triceps muscle, isokinetic strength, Achilles tendon Total Rupture Score (ATRS), and the Victorian Institute of Sports Assessment-Achilles (VISA-A) score were compared between the 2 groups. RESULTS:The average follow-up time was 40.0 ± 10.2 months. The operation time and complication rate in the MI group were significantly lower than in the OR group (P < .001, P = .031). The ATRS score (P = .015), VISA-A score (P = .002), isokinetic strength (60 degrees/second: P = .006; 180 degrees/second: P = .036), SWE values (P = .007), and CSA of Achilles tendon (P = .043) in the MI group were significantly higher than the OR group. SWE values were significantly positively correlated with the ATRS score (r = 0.294, P < .001) and the VISA-A score (r = 0.304, P < .001). And a significant negative correlation was found between Achilles tendon extension length and peak torque (60 degrees/second: r = -0.309, P < .001; 180 degrees/second: r = -0.218, P = .013). CONCLUSION:Compared with the open repair giftbox technique, the minimally invasive paratenon protection technique was associated with likely marginally clinically significant improved clinical outcome scores, greater isokinetic strength, and better mechanical properties of the Achilles tendon.

Krackow suturing and suture bridge technique was compared with Kirschner-Wire (K-wire) tension band and patella cerclage for the fixation of inferior pole patella fracture. This was a retrospective study of 47 patients with inferior pole patella fractures who underwent fixation procedures at our hospital between January 2019 and May 2022, of whom 25 had Krackow suturing combined with the suture-bridge technique (GROUP 1), and 22 received a K-wire tension band combined with patellar cerclage (GROUP 2). We compared the operative time, reoperation rate, Böstman score, knee range of motion (ROM), fracture-healing time, Insall–Salvati index, complications and hospital expenses between the two groups. The average follow-up period was 23.1 ± 5.8 months. The complication and reoperation rates in the GROUP 2 were significantly higher than those in the GROUP 1 (P = 0.023 and P < 0.001). While the GROUP 1 has lower hospital expenses than GROUP 2 (P < 0.001). However, significant differences were not found regarding the Böstman score, knee ROM, Insall–Salvati index, fracture-healing time, and operation time between the two groups. Both Krackow suturing combined with the suture-bridge technique and the K-wire tension band technique can achieve comparable clinical efficacy in stably fixing inferior patellar pole fractures, subsequently allowing an early commencement of rehabilitation exercise, while the suture-bridge technique can also reduce the incidence of complications, hospital expenses and the need for reoperation surgery. This study was registered on https://www.chictr.org.cn (registration No. ChiCTR2300072069, 2023/06/01, retrospectively registered). Informed consent was obtained from all individual participants included in the study.

Objective:To explore a new algorithmic treatment for Congenital Contracture of the Ulnar Digits based on pathological classification. Methods:A retrospective analysis was performed on 7 patients with Congenital contracture of the ulnar digits who were admitted and treated from 2019 to 2024, and their clinical characteristics were summarized. During the final follow-up visit, the patients' finger joint range of motion and flexor digitorum profundus muscle strength were evaluated. Hand function was assessed utilizing the hand function rating criteria established by Wang et al., while the patients' overall satisfaction was surveyed. Results:All 7 patients completed the scheduled follow-up, with durations ranging from 6 to 74 months and a mean of 26 months. All patients achieved primary wound healing, and no adverse events or complications were documented. At the final follow-up visit, with their wrists maintained in a neutral position, all patients exhibited active extension of the affected fingers to 0° without residual tension, while all digits demonstrated unimpeded flexion. Muscle strength assessment of the flexor digitorum profundus revealed that 5 patients attained Grade 5, with the remaining 2 patients rated at Grade 4. Furthermore, hand function evaluation yielded the following findings: 5 cases were categorized as "excellent" and 2 as "good," resulting in an excellent-to-good rate of 100 %. All patients expressed satisfaction with both the functional recovery of their hands and the cosmetic outcome. Conclusion:Congenital contracture of the ulnar digits can be classified into three pathological subtypes-osteophyte subtype, fibrosis subtype and mixed subtype-through the combination of clinical evaluation and surgical exploration. By adopting different treatment algorithms for different pathological subtypes and providing professional rehabilitation therapy, patients can achieve favorable therapeutic outcomes. Evidence level:Level IV.

BACKGROUND:The classic surgical technique of the 15-mm incision minimally invasive approach is not suitable for AO 23-B3 distal radius fractures (abbreviated B3). We have modified this technique for B3. This study aimed to investigate the efficacy of the modified 15-mm incision minimally invasive approach with the conventional ORIF approach in the treatment of B3. METHODS:This retrospective study included 62 patients with B3 who underwent surgical treatment from January 2020 to May 2024, including 31 patients undergoing the modified 15-mm incision minimally invasive approach (M group) and 31 patients undergoing the conventional ORIF approach (C group). The two groups had similar baseline characteristics (P > 0.05). The perioperative data, follow-up data, and imaging results of the two groups were compared. At the last follow-up, the limb function was assessed using the PRWE and DASH scores. RESULTS:In the C group, 1 patient experienced infection and 1 patient experienced complex regional pain syndrome, whereas in the M group, there were no such patients. In the M group, the incision length, intraoperative bleeding, hospital stay, hospitalization expenses, swelling, and VAS on postoperative days 2 and 7, flexion-extension, ulnar-radial deviation and pronation-supination at postoperative 3 months, and pronation-supination ROM in 12-24 months of follow-up were superior, but the surgical and fluoroscopy time was longer compared to the C group (P < 0.05). There was no difference between the two groups in terms of fracture reduction, fracture healing time, full weight-bearing time, complications, and flexion-extension ROM, PRWE and DASH in the last follow-up (P > 0.05). CONCLUSION:Both methods were effective for treating B3. The M group was superior in terms of aesthetic appeal of the incision, surgical trauma and associated risks, hospital stay, early recovery, and final rotational function, which are consistent with the principles of MIPO and rapid recovery, but requires longer surgical and fluoroscopy time.

Diabetic wound healing presents unique challenges, including impaired angiogenesis, prolonged inflammation, and delayed re-epithelialization. Advancements in tissue engineering offer promising solutions through cell/drug-based therapies. Exosomes (Exo) derived from hypoxia-preconditioned adipose-derived stem cells (ADSCs) have gained attention for their potential to address these complex issues in diabetic wounds. Existing strategies for Exo delivery aim to overcome drawbacks associated with conventional administration methods, including rapid loss of activity, frequent dosing, and off-target effects. However, complexities in fabrication, undesirable components within the delivery system, and unforeseen outcomes have hindered the efficacy of these approaches. Thus, an in situ formed hydrogel is engineered using click chemistry to facilitate the convenient encapsulation of hypoxia-induced Exo. The hydrogel swiftly transitioned into a gel state upon mixing and facilitated the controlled release of Exo at various loading dosages. Through systematic screening of Exo-hydrogel formulations, it is demonstrated that the encapsulated Exo retained their bioactivity, exhibits therapeutic efficacy in vitro via scratch and tube formation assays. Further, the optimal Exo-hydrogel promotes accelerated wound healing while preventing scar formation in a diabetic rat wound model. The Exo-loaded hydrogel represents a promising approach for efficient Exo delivery in wound healing applications and holds potential for broader applications in diverse medical fields.

Schematic illustration of the mechanism by which an IM promotes bone formation. FMOD secreted by the IM promotes osteogenesis of BMSCs and angiogenesis of HUVECs by inhibiting the TGF-β/SMAD signaling pathway, thus facilitating bone formation.

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.