Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury.

Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism.

A versatile engineered extracellular vesicle platform simultaneously targeting and eliminating senescent stromal cells and tumor cells to promote tumor regression.

Chemotherapy is an important therapeutic approach for malignant tumors for it triggers apoptosis of cancer cells. However, chemotherapy also induces senescence of stromal cells in the tumor microenvironment to promote tumor progression. Strategies aimed at killing tumor cells while simultaneously eliminating senescent stromal cells represent an effective approach to cancer treatment. Here, we developed an engineered Src-siRNA delivery system based on small extracellular vesicles (sEVs) to simultaneously eliminate senescent stromal cells and tumor cells for cancer therapy. The DSPE-PEG-modified urokinase plasminogen activator (uPA) peptide was anchored to the membranes of induced mesenchymal stem cell-derived sEVs (uPA-sEVs), and Src siRNA was loaded into the uPA-sEVs by electroporation (uPA-sEVs-siSrc). The engineered uPA-sEVs-siSrc retained the basic sEVs properties and protected against siSrc degradation. uPA peptide modification enhanced the sEVs with the ability to simultaneously target doxorubicin-induced senescent stromal cells and tumor cells. Src silencing by uPA-sEVs-siSrc induced apoptosis of both senescent stromal cells and tumor cells. The uPA-sEVs-siSrc displayed preferential tumor accumulation and effectively inhibited tumor growth in a tumor xenograft model. Furthermore, uPA-sEVs-siSrc in combination with doxorubicin significantly reduced the senescence burden and enhanced the therapeutic efficacy of chemotherapy. Taken together, uPA-sEVs-siSrc may serve as a promising therapy to kill two birds with one stone, not only killing tumor cells to achieve remarkable antitumor effect, but also eliminating senescent cells to enhance the efficacy of chemotherapeutic agent in tumor regression.

AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling.

Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, and autonomic functions below the level of injury. Limitations of current therapeutic approaches prompt an investigation into therapeutic angiogenesis through persistent local expression of proangiogenic factors. Here, we investigated whether overexpression of adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) in mouse SCI promoted locomotor function recovery, and whether the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA was injected at the T10 level to induce VEGFA overexpression. Neurofunctional, histological, and biochemical assessments were done to determine tissue damage and/or recovery of neuromuscular and behavioral impairments. Daily injections of the PI3K/Akt pathway inhibitor LY294002 were made to assess a possible mechanism. AAV-VEGFA overexpression dramatically improved locomotor function and ameliorated pathological injury caused by SCI. Improved motor-evoked potentials in hindlimbs and more spinal CD31-positive microvessels were observed in AAV-VEGFA-overexpressing mice. LY294002 reduced PI3K and Akt phosphorylation levels and attenuated AAV-VEGFA-related improvements. In conclusion, sustained local AAV-mediated VEGFA overexpression in spinal cord can significantly promote angiogenesis and ameliorate locomotor impairment after SCI in a contusion mouse model through activation of the PI3K/Akt signaling pathway.

Anterior transposition and positioning via helix sling method in cubital tunnel syndrome: An open-label, retrospective trial of maximum 5-year follow-up.

Background: Ulnar nerve transposition is used for cubital tunnel syndrome (CuTS) with nerve instability. The aim is to report a modified technique for ulnar nerve transposition using medial intermuscular septum and Osborne's ligament as a double-strand helix sling to recreate a sliding channel for the ulnar nerve and the functional outcomes at follow-ups. Methods: Twenty-five patients with persistent CuTS underwent nerve release and subcutaneous transposition from January 2017 to January 2022 in our institute. Among them, 9 patients were excluded due to incomplete medical records, lack of follow-up history, or bilateral limb numbness. The medial intermuscular septum with one end attached was excised to rebuild a tension-free double-strand helix sling by anchoring at the residue of Osborne's ligament. The modified Mc-Gowan classification was applied to evaluate the disease severity preoperatively. The quick disability of arm and shoulder and hand (quickDASH) questionnaire and visual analogue scale (VAS) scores were used to evaluate pre- and postoperative symptoms. Ultrasound imaging was utilized for nerve structure evaluation before surgery and at follow-ups. Results: Sixteen out of twenty-five patients received follow-ups postoperatively (ranging from 9 to 69 months, 36 months in average). No findings indicated subluxation of ulnar nerve or recompression by ultrasound imaging examination. According to quickDASH and VAS scores and physical examination, 14 out of 16 patients showed postoperative improvement in symptoms and function at final follow-ups. Interpretation: In this modified technique, the medial intermuscular septum and Osborne's ligament can create tension-free helix sling for stable and smooth sliding and preventing subluxation after nerve transposition, which is highly effective and safe for CuTS treatment.

Development and external validation of a prediction model for digit replantation failure after traumatic amputations based on a prospective multicenter cohort.

BACKGROUND: Failure of digit replantation after traumatic amputation is difficult to predict. We aimed to develop a prognostic model to better identify factors that better predict replantation failure following traumatic digit amputation. MATERIALS AND METHODS: In this multicenter prospective cohort, we identified patients who had received digit replantation between January 1, 2015, and January 1, 2019. Univariable and multivariable analyses were performed successively to identify independently predictive factors for failure of replanted digit. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. This model was then internally validated with bootstrap resampling and further externally validated in validation cohort. RESULTS: Digit replantation was failed in 101 of 1062 (9.5%) digits and 146 of 1156 digits (12.6%) in the training and validation cohorts, respectively. We found that six independent prognostic variables were associated with digit replantation failure: age, mechanism of injury, ischemia duration, smoking status, amputation pattern (complete or incomplete), and surgeon's experience. The prediction model achieved good discrimination, with concordance indexes of 0.81 (95% CI, 0.76-0.85) and 0.70 (95% CI, 0.65-0.74) in predicting digit failure in the training and validation cohorts, respectively. Calibration curves were well-fitted for both training and validation cohorts. CONCLUSIONS: The proposed prediction model effectively predicted the failure rate of digit replantation for individual digits of all patients. It could assist in selecting the most suitable surgical plan for the patient.

Injectable Nano-Micro Composites with Anti-bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis.

The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti-infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano-micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug-loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano-micro composite called "CaP@MS-Oligo-Van" is synthesized. The porous CaP@MS-Oligo-Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS-Oligo-Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.

Efficacy of EDTA-NS irrigation in eradicating Staphylococcus aureus biofilm-associated infection.

Aims: To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections. Methods: EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Staphylococcus aureus biofilms on Matrigel-coated glass and two materials widely used in orthopaedic implants (Ti-6Al-4V and highly cross-linked polyethylene (HXLPE)). To assess the efficacy of biofilm dispersion, crystal violet staining biofilm assay and colony counting after sonification and culturing were performed. The results were further confirmed and visualized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). We then investigated the efficacies of EDTA-NS irrigation in vivo in rat and pig models of biofilm-associated infection. Results: When 10 mM or higher EDTA-NS concentrations were used for ten minutes, over 99% of S. aureus biofilm formed on all three types of materials was eradicated in terms of absorbance measured at 595 nm and colony-forming units (CFUs) after culturing. Consistently, SEM and CSLM scanning demonstrated that less adherence of S. aureus could be observed on all three types of materials after 10 mM EDTA-NS irrigation for ten minutes. In the rat model, compared with NS irrigation combined with rifampin (Ti-6Al-4V wire-implanted rats: 60% bacteria survived; HXLPE particle-implanted rats: 63.3% bacteria survived), EDTA-NS irrigation combined with rifampin produced the highest removal rate (Ti-6Al-4V wire-implanted rats: 3.33% bacteria survived; HXLPE particle-implanted rats: 6.67% bacteria survived). In the pig model, compared with NS irrigation combined with rifampin (Ti-6Al-4V plates: 75% bacteria survived; HXLPE bearings: 87.5% bacteria survived), we observed a similar level of biofilm disruption on Ti-6Al-4V plates (25% bacteria survived) and HXLPE bearings (37.5% bacteria survived) after EDTA-NS irrigation combined with rifampin. The in vivo study revealed that the biomass of S. aureus biofilm was significantly reduced when treated with rifampin following irrigation and debridement, as indicated by both the biofilm bacterial burden and crystal violet staining. EDTA-NS irrigation (10 mM/10 min) combined with rifampin effectively removes S. aureus biofilm-associated infections both in vitro and in vivo. Conclusion: EDTA-NS irrigation with or without antibiotics is effective in eradicating S. aureus biofilm-associated infection both ex and in vivo.

Free peroneal artery perforator flap for reconstruction of traumatic limb soft tissue defects: A retrospective case series study.

BACKGROUND: The free peroneal artery perforator (FPAP) flap is used for soft tissue defects after burns and trauma. However, the use of FPAP flaps to repair limb soft tissue defects for immediate reconstruction was rarely reported previously. Therefore, the purpose of this report is to evaluate free peroneal artery perforator flap to reconstruct traumatic limb soft tissue defects for immediate reconstruction. PATIENTS AND METHODS: A total of 25 cases of limb soft tissue defects undergoing immediate reconstruction of FPAP flap transfer were retrospectively evaluated from January 2019 to June 2019 in our institute. The locations of defects included the palm (10 cases), finger (5 cases), foot (7 cases), ankle (2 cases) and wrist (1 case). The sizes of defect varied from 3 × 2 cm to 15 × 7 cm (54.1 cm2 in average). Flaps were harvested based on the peroneal perforator vessels, initially marked using hand-held Doppler. RESULTS: Average size of harvested flap was 9.7 × 6.2 cm (ranging from 3.5 × 2 cm to 16 × 8 cm). All perforators were harvested from the peroneal artery and the arterial diameter ranged from 0.8 to 1.7 mm. The average pedicle length was 3.04 cm (range, 1.85-4.75 cm). Five vascular thrombosis were found including three cases of arterial thrombosis and two cases of venous thrombosis which were successfully salvaged by re-operation and vein graft. Satisfying functional outcome and acceptable appearance were achieved at 6 months or longer after surgery (range, 6-15 months, 12 months in average). All flaps survived at the end-point. CONCLUSIONS: The FPAP flap is a reliable and thin fasciocutaneous flap, which can be used for repairing limb soft tissue defects. The FPAP flap can be used for covering defects with various appearances, locations, and sizes.

Altered cortical thickness and structural covariance networks in upper limb amputees: A graph theoretical analysis.

BACKGROUND: The extensive functional and structural remodeling that occurs in the brain after amputation often results in phantom limb pain (PLP). These closely related phenomena are still not fully understood. METHODS: Using magnetic resonance imaging (MRI) and graph theoretical analysis (GTA), we explored how alterations in brain cortical thickness (CTh) and structural covariance networks (SCNs) in upper limb amputees (ULAs) relate to PLP. In all, 45 ULAs and 45 healthy controls (HCs) underwent structural MRI. Regional network properties, including nodal degree, betweenness centrality (BC), and node efficiency, were analyzed with GTA. Similarly, global network properties, including global efficiency (Eglob), local efficiency (Eloc), clustering coefficient (Cp), characteristic path length (Lp), and the small-worldness index, were evaluated. RESULTS: Compared with HCs, ULAs had reduced CThs in the postcentral and precentral gyri contralateral to the amputated limb; this decrease in CTh was negatively correlated with PLP intensity in ULAs. ULAs showed varying degrees of change in node efficiency in regional network properties compared to HCs (p < 0.005). There were no group differences in Eglob, Eloc, Cp, and Lp properties (all p > 0.05). The real-worldness SCN of ULAs showed a small-world topology ranging from 2% to 34%, and the area under the curve of the small-worldness index in ULAs was significantly different compared to HCs (p < 0.001). CONCLUSION: These results suggest that the topological organization of human CNS functional networks is altered after amputation of the upper limb, providing further support for the cortical remapping theory of PLP.

Clinical Characteristics, Mechanism, and Outcome of Humeral Shaft Fractures Sustained during Arm Wrestling in Young Men: A Retrospective Study.

OBJECTIVE: Humeral fractures are common in arm wrestling and other sports and military activities requiring similar movements; however, the precise mechanism is poorly understood. Here, we present an overview of the characteristics, possible mechanisms, and treatment of humeral shaft fractures sustained during arm wrestling. METHODS: We reviewed 8 years (January 2013 to January 2021) of medical records and retrospectively analyzed data from 27 patients with humeral shaft fractures sustained during arm wrestling. The clinical data included sex, age, affected arm, alcohol consumption, muscle warm-up, history of competitive participation, opponents' characteristics, wrist position, and post-fracture radial nerve injuries. The fracture configurations were radiographically assessed and analyzed. Surgical management included single or dual plating. Scores on the Disability of the Arm, Shoulder, and Hand questionnaire (DASH) were evaluated preoperatively and postoperatively at the last follow-up visit. RESULTS: All fractures sustained during arm wrestling were spiral fractures of the distal third of the humerus. Of these, 11 were 12-A1 type and 16 were 12-B2 type with a wedge fragment. The two subtypes differed in the total fracture line length (12-A1: 0.18 ± 0.04; 12-B2: 0.23 ± 0.04; P < 0.001). The radial nerve injury rate was 0/11 (0%) in patients with 12-A1 type fractures and 7/16 (43.8%) in patients with 12-B2 type fractures (P = 0.011). Most patients were young men (mean age, ~25 years) with a history of competitively participating in arm wrestling for >2 years. Cold seasonal temperatures and a lack of warm-ups increased the risk of injury. All patients showed improved DASH scores at the last follow-up (12-A1:77.82 ± 5.14 to 10.25 [5.38]; 12-B2:78.91 ± 7.46 to 8.95 [3.17]; P < 0.001). No significant differences were observed among the different surgical treatments. CONCLUSIONS: Individuals who participated in arm wrestling were at risk of humeral shaft fractures (type 12-A1 or 12-B2). The 12-B2 type occurs with a wedge fragment and is frequently accompanied by radial nerve injuries. The characteristics of arm-wrestling fractures and the mechanism(s) underlying these fractures can help orthopedic surgeons understand the causes of these fractures and similar fractures sustained in traditional sports. This understanding will help surgeons choose more effective surgical treatments that will result in more desirable functional outcomes and a faster return to work.

Accelerated aging in articular cartilage by ZMPSTE24 deficiency leads to osteoarthritis with impaired metabolic signaling and epigenetic regulation.

Osteoarthritis (OA) is an age-related degenerative disease without disease-modifying therapy. The lack of aging-induced osteoarthritis models makes the discovery of therapeutic drugs more challenging. The deficiency of ZMPSTE24 could induce Hutchinson-Gilford progeria syndrome (HGPS), a genetic disorder of rapid aging. However, the relationship between HGPS and OA remains unclear. Our results found that the expression of Zmpste24 was decreased in the articular cartilage during the aging process. Zmpste24 knockout mice, Prx1-Cre; Zmpste24fl/fl mice and Col2-CreERT2; Zmpste24fl/fl mice displayed OA phenotype. Loss of Zmpste24 in articular cartilage could exacerbate the occurrence and development of osteoarthritis. Transcriptome sequencing revealed that deletion of Zmpste24 or accumulation of progerin affects chondrocyte metabolism, inhibits cell proliferation and promotes cell senescence. Using this animal model, we elucidate the upregulation of H3K27me3 during chondrocyte senescence and discover the molecular mechanism by which lamin A mutant stabilizes EZH2 expression. The construction of aging-induced osteoarthritis models and the elucidation of the signaling pathways and molecular mechanisms of articular chondrocyte senescence would benefit the discovery and development of new drugs for OA.

Risk factors for deep vein thrombosis in patients with pelvic or lower-extremity fractures in the emergency intensive care unit.

Introduction: This study aimed to investigate the incidence of deep vein thrombosis (DVT) in patients with pelvic or lower-extremity fractures in the emergency intensive care unit (EICU), explore the independent risk factors for DVT, and investigate the predictive value of the Autar scale for DVT in these patients. Methods: The clinical data of patients with single fractures of the pelvis, femur, or tibia in the EICU from August 2016 to August 2019 were retrospectively examined. The incidence of DVT was statistically analyzed. Logistic regression was used to analyze the independent risk factors for DVT in these patients. The receiver-operating characteristic (ROC) curve was used to evaluate the predictive value of the Autar scale for the risk of DVT. Results: A total of 817 patients were enrolled in this study; of these, 142 (17.38%) had DVT. Significant differences were found in the incidence of DVT among the pelvic fractures, femoral fractures, and tibial fractures (P < 0.001). The multivariate logistic regression analysis showed multiple injuries (OR = 2.210, 95% CI: 1.166-4.187, P = 0.015), fracture site (compared with tibia fracture group, femur fracture group OR = 4.839, 95% CI: 2.688-8.711, P < 0.001; pelvic fracture group OR = 2.210, 95% CI: 1.225-3.988, P = 0.008), and Autar score (OR = 1.198, 95% CI: 1.016-1.353, P = 0.004) were independent risk factors for DVT in patients with pelvic or lower-extremity fractures in the EICU. The area under the ROC curve (AUROC) of the Autar score for predicting DVT was 0.606. When the Autar score was set as the cutoff value of 15.5, the sensitivity and specificity for predicting DVT in patients with pelvic or lower-extremity fractures were 45.1% and 70.7%, respectively. Discussion: Fracture is a high-risk factor for DVT. Patients with a femoral fracture or multiple injuries have a higher risk of DVT. In the case of no contraindications, DVT prevention measures should be taken for patients with pelvic or lower-extremity fractures. Autar scale has a certain predictive value for the occurrence of DVT in patients with pelvic or lower-extremity fractures, but it is not ideal.

Free fillet flap transplantation using amputated upper limbs for shoulder defect coverage and joint function salvage in emergency treatment-A case report.

INTRODUCTION AND IMPORTANCE: Severe limb trauma results in mangled extremities, amputation, uncovered wound and delayed healing. The rapid development of flap transplantation concept and technique leads to applications of free flap in the salvage of limb and articular appearance and functions. This report discusses the case of a patient with acute shoulder avulsion and smashed injuries and evaluates the feasibility and safety of free fillet flap transplantation in emergency treatment. CASE PRESENTATION: A 44-year-old man presented with acute traumatic severing injury to the left arm. We performed free fillet flap transplantation from the amputated forearms to retain the structure of shoulder joint and coverage of humerus in a patient who suffered from acute shoulder avulsion and smashed injuries. Moreover, we evaluated the long-term outcomes at 2-year follow-up and confirmed the functional adaptivity of proximal stump of the shoulder joint. CLINICAL DISCUSSION: The free fillet flap application is an important and advanced technique to cover large areas of skin and soft tissue defects in a mangled upper limb. It requires an experienced microsurgeon to achieve vessel reconnection, flap transfer and wound repair. In such an emergency case like this one, it calls for collaboration between different departments to work out a delicate and comprehensive plan in order to obtain the best possible result for saving patients. CONCLUSION: The free fillet flap transfer in this report is feasible and useful for shoulder defect coverage and joint function salvage in emergency treatment.

iPSC-sEVs alleviate microglia senescence to protect against ischemic stroke in aged mice.

The polarization of microglia plays an important role in the outcome of ischemic stroke (IS). In the aged population, senescent microglia show a predominant pro-inflammatory phenotype, which leads to worse outcomes in aged ischemic stroke compared to young ischemic stroke. Recent research demonstrated that inducible pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) possess the significant anti-ageing ability. We hypothesized that iPSC-sEVs could alleviate microglia senescence to regulate microglia polarization in aged ischemic stroke. In this study, we showed that treatment with iPSC-sEVs significantly alleviated microglia senescence as indicated by the decreased senescence-associated proteins including P16, P21, P53, and γ-H2AX as well as the activity of SA-ß-gal, and inhibited pro-inflammatory activation of microglia both in vivo and in vitro. Furthermore, iPSC-sEVs shifted microglia from pro-inflammatory phenotype to anti-inflammatory phenotype, which reduced the apoptosis of neurons, and improved the outcome of aged stroke mice. Mechanism studies showed that iPSC-sEVs reversed the loss of Rictor and downstream p-AKT (s473) in senescent microglia, which was involved in the senescence and pro-inflammatory phenotype regulation of microglia. Inhibition of Rictor abolished the iPSC-sEVs-afforded phosphorylation of AKT and alleviation of inflammation of senescent microglia. Proteomics results indicated that iPSC-sEVs carried transforming growth factor-ß1 (TGF-ß1) to upregulate Rictor and p-AKT in senescent microglia, which could be hindered by blocking TGF-ß1. Taken together, our work demonstrates iPSC-sEVs reverse the senescent characteristic of microglia in aged brains and therefore improve the outcome after stroke, at least, via delivering TGF-ß1 to upregulate Rictor and p-AKT. Our data suggest that iPSC-sEVs might be a novelty therapeutic method for aged ischemic stroke and other diseases involving senescent microglia.

Relative efficacy of three different tendon repairs in complete flexor digitorum profundus laceration in Zone I: A randomized controlled study.

Hand flexor tendon injuries are common and biomechanically challenging to achieve good functional outcomes. Several approaches using the Pennington-modified Kessler repair technique have been attempted, but high-level evidence is still lacking. Here, we evaluated the relative efficacy of three versions of the Pennington-modified Kessler technique in repairing complete flexor digitorum profundus (FDP) laceration in Zone 1. We conducted a 2-year, single-center, double-blind, randomized clinical trial involving 85 patients with 105 digits enrolled between June 1, 2017 and January 1, 2019. Eligible participants were 20-60 years of age and underwent tendon repair in the acute phase for complete FDP laceration distal to the insertion of the superficial flexor tendon. The digits were randomized 1:1:1 to three treatment groups: (1) Pennington-modified Kessler repair; (2) Pennington-modified Kessler repair followed by circumferential tendon suture; or (3) Pennington-modified Kessler repair followed by circumferential epitenon suture. The primary endpoint was total active range of motion (TAROM) at 2 years after the initial surgery. The secondary endpoint was the reoperation rate. Compared with group 1, both techniques for peripheral suture were associated with a decrease in TAROM at 2 years after surgery. The total reoperation rates of the three groups were 11.4%, 18.2%, and 17.6%, and we found no significant differences among the three groups possibly due to the limited sample size. Unexpectedly, among participants with complete FDP laceration in Zone I, both circumferential-tendon and circumferential-epitenon sutures caused worsening of TAROM after 2 years. No conclusions can be drawn regarding reoperation rates among the groups. Level of evidence: Therapeutic level I.

Triplanar osteotomy combined with proximal tibial transverse transport to accelerate healing of recalcitrant diabetic foot ulcers.

BACKGROUND: Management of recalcitrant diabetic foot ulcers remains challenging. Tibial transverse transport (TTT) is an effective method for enhancing the healing of foot ulcers. This retrospective study reports a novel triplanar osteotomy in the tibia and assesses the clinical outcomes of TTT for diabetic foot ulcers. METHODS: Fifty-nine patients with recalcitrant diabetic foot ulcers were divided into the TTT (32 patients) and control (27 patients) groups. In the TTT group, the patients underwent triplanar osteotomy of the proximal tibia, followed by 2 weeks of medial distraction and 2 weeks of lateral distraction. In the control group, the patients received conventional management, including debridement, revascularization, and reconstruction. Ulcer healing and healing time, amputation, recurrence, and complications were assessed at an 18-month follow-up visit. Computed tomography angiography (CTA) was used to evaluate vessel changes in the lower limbs of patients in the TTT group. RESULTS: The TTT group was superior to the control group in the healing rate (90.6% [29/32] vs. 66.7% [18/27]) and the healing time (4.6 ± 1.7 months vs. 7.4 ± 2.5 months), respectively. The proportions of amputation and recurrence in the TTT group were lower than that in the control group, without statistical difference. After triplanar osteotomy and transverse distraction, CTA demonstrated an increase in small vessels in the wound and ipsilateral limb. All patients achieved satisfactory union of the osteotomized bone fragment after removal of the external fixator. CONCLUSIONS: Triplanar osteotomy combined with proximal tibial transverse distraction accelerates wound healing and limb salvage caused by severe and recalcitrant diabetic foot ulcers. Triplanar osteotomy not only increases the bone contact area, which is beneficial for rapid bone reconstruction, but also preserves the vascularization of the bone fragment and substantially facilitates capillary angiogenesis during distraction. These results suggest that triplanar osteotomy followed by tibial transverse distraction is an effective method for treating diabetic foot ulcers.

Comprehensive analysis of potential cellular communication networks in advanced osteosarcoma using single-cell RNA sequencing data.

Osteosarcoma (OS) is a common bone cancer in children and adolescents, and metastasis and recurrence are the major causes of poor treatment outcomes. A better understanding of the tumor microenvironment is required to develop an effective treatment for OS. In this paper, a single-cell RNA sequencing dataset was taken to a systematic genetic analysis, and potential signaling pathways linked with osteosarcoma development were explored. Our findings revealed 25 clusters across 11 osteosarcoma tissues, with 11 cell types including "Chondroblastic cells", "Osteoblastic cells", "Myeloid cells", "Pericytes", "Fibroblasts", "Proliferating osteoblastic cells", "Osteoclasts", "TILs", "Endothelial cells", "Mesenchymal stem cells", and "Myoblasts". The results of Cell communication analysis showed 17 potential cellular communication networks including "COLLAGEN signaling pathway network", "CD99 signaling pathway network", "PTN signaling pathway network", "MIF signaling pathway network", "SPP1 signaling pathway network", "FN1 signaling pathway network", "LAMININ signaling pathway network", "FGF signaling pathway network", "VEGF signaling pathway network", "GALECTIN signaling pathway network", "PERIOSTIN signaling pathway network", "VISFATIN signaling pathway network", "ITGB2 signaling pathway network", "NOTCH signaling pathway network", "IGF signaling pathway network", "VWF signaling pathway network", "PDGF signaling pathway network". This research may provide novel insights into the pathophysiology of OS's molecular processes.

Modelling osteoarthritis in mice via surgical destabilization of the medial meniscus with or without a stereomicroscope.

AIMS: To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope. METHODS: Based on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system. RESULTS: Surgical DMM with or without stereomicroscope led to decrease in the mean of weightbearing percentages (-20.64% vs -21.44%, p = 0.792) and paw withdrawal response thresholds (-21.35% vs -24.65%, p = 0.327) of the hind limbs. However, the coefficient of variation (CV) of weight-bearing percentages and paw withdrawal response thresholds in naked-eye group were significantly greater than that in the microscope group (19.82% vs 6.94%, p < 0.001; 21.85% vs 9.86%, p < 0.001). The gait analysis showed a similar pattern. Cartilage degeneration was observed in both DMM-surgery groups, evidenced by increased OARSI scores (summed score: 11.23 vs 11.43, p = 0.842), but the microscope group showed less variation in OARSI score than the naked-eye group (CV: 21.03% vs 32.44%; p = 0.032). CONCLUSION: Although surgical DMM aided by stereomicroscope is technically difficult, it produces a relatively more homogeneous OA model in terms of the discrete degree of pain behaviours and histopathological grading when compared with surgical DMM without stereomicroscope.Cite this article: Bone Joint Res 2022;11(8):518-527.

[Advances of the role of mitochondrial dysfunction in the spinal cord injury and its relevant treatments].

Objective: To review the advances of the role of mitochondrial dysfunction in the spinal cord injury (SCI) and its relevant treatments. Methods: Focusing on various mechanisms of mitochondrial dysfunction, recent relevant literature at home and abroad was identified to summarize the therapeutic strategies for SCI. Results: Mitochondrial dysfunction is mainly manifested in abnormalities in mitochondrial energy metabolism, mitochondrial oxidative stress, mitochondrial-mediated apoptosis, mitophagy, mitochondrial permeability transition, and mitochondrial biogenesis, playing a vital role in the development of SCI. Drug that enhanced mitochondrial function have been proved beneficial for the treatment of SCI. Conclusion: Mitochondrial dysfunction can serve as a potential therapeutic target for SCI, providing ideas and basis for the development of SCI therapeutic candidates in the future.