Functionalized Blood Small Extracellular Vesicles with Polydopamine Nanoparticles for Chemo-Thermal Therapy.

Small extracellular vesicles (sEVs) hold considerable promise for drug delivery due to their natural origin and inherent qualities. However, their clinical application is impeded by two main challenges: low yield and potential side effects. Therefore, it is crucial to obtain substantial quantities of sEVs that adhere to rigorous biosafety standards to ensure successful translation into clinical practice. To address this need, we propose exploring optimized methods for sourcing and separating sEVs, taking inspiration from clinical blood transfusion. In particular, we have identified blood sEVs as a viable alternative and developed a novel separation technique for their isolation. Our approach involves incubating dopamine solution with serum, resulting in the formation of polydopamine (PDA) nanoparticles on the surface of blood sEVs. These nanoparticles have minimal impact on blood sEVs, facilitating their easy separation under standard centrifugal conditions with high purity. This innovative technique enables the development of nanocarriers using blood sEVs with efficient drug-loading capabilities and enhanced pharmacokinetics. Additionally, the incorporation of PDA nanoparticles imparts a photothermal effect to the nanomedicines, enabling the integration of chemotherapy and photothermal therapy. Moreover, the photothermal effect holds the potential to facilitate the membrane fusion of sEVs and cells. In summary, our straightforward surface functionalization technique utilizing PDA effectively isolates blood sEVs and enables chemo-thermal tumor therapy. This approach significantly enhances the feasibility of translating sEV-based nanomedicines into clinical applications.

Bio-mechanical effects of femoral neck system versus cannulated screws on treating young patients with Pauwels type III femoral neck fractures: a finite element analysis.

INTRODUCTION: As a novel internal fixation for femoral neck fractures, the femoral neck system has some advantages for young Pauwels type III femoral neck fractures without clear biomechanical effects and mechanisms. Thus, the objection of the study is to realize the biomechanical effects and mechanism of FNS cannulated screws on treating young patients with Pauwels type III femoral neck fractures compared to cannulated screws which are commonly used for femoral neck fractures by finite element analysis. METHODS: Firstly, the model of young Pauwels type III femoral neck fractures, femoral neck system (FNS), and three cannulated screws (CS) arranged in an inverted triangle were established, and the internal fixations were set up to fix young Pauwels type III femoral neck fractures. Under 2100 N load, the finite element was performed, and the deformation, peak von Mises stress (VMS), and contact at fracture segments were recorded to analyze the biomechanical effects and mechanism of FNS and three-CS fixing young Pauwels type III femoral neck fractures. RESULTS: Compared to three-CS, the deformation of the whole model, internal fixation, and fracture segments after FNS fixation were lower, and the peak VMS of the whole model and the internal fixation after FNS were higher with lower peak VMS of the distal femur and the fracture segments. With a sticking contact status, the contact pressure at fracture segments after FNS fixation was lower than that of three-CS. CONCLUSIONS: FNS can provide better mechanical effects for young patients with Pauwels type III femoral neck fractures, which may be the mechanical mechanism of the clinical effects of FNS on femoral neck fracture. Although there is high stress on FNS, it is still an effective and safe internal fixation for young patients with Pauwels type III femoral neck fractures.

Neuroprotective effects of tetramethylpyrazine on spinal cord injury-Related neuroinflammation mediated by P2X7R/NLRP3 interaction.

OBJECTIVE: The inflammatory response is acknowledged as a crucial pathological aspect of spinal cord injury (SCI). Tetramethylpyrazine (TMP) has been demonstrated to possess neuroprotective properties within the central nervous system via its anti-inflammatory mechanisms. This study aims to investigate the molecular mechanism by which TMP alleviates SCI from an anti-inflammatory standpoint. METHODS: The SCI model was established using the MASCIS impactor device. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was utilised to assess rat locomotion. Nissl and Golgi staining were used to observe neuron and dendritic spine morphology, respectively. A transmission electron microscope was used to observe the microcosmic morphology of the axon. ELISA kits were used to measure the concentrations of IL-1ß and IL-18 in the spinal cord. Immunofluorescence staining was used to detect P2X7R+/IBA-1+ cells, and Western blot and RT-qPCR were used to analyze the protein and mRNA expression of P2X7R in the spinal cord. Additionally, Western blot was used to detect NLRP3 and Cleaved-Caspase-1 (p20), the critical proteins in the NLRP3 inflammasome pathway. RESULTS: TMP ameliorated the microcosmic morphology of the axon and had an inhibitory effect on the concentrations of IL-1ß and IL-18 after SCI. Furthermore, TMP inhibited the expression of both P2X7R and critical proteins of the NLRP3 inflammasome pathway on microglia after SCI. The aforementioned effects of TMP exhibit similarities to those of BBG (P2X7R antagonist); however, they can be effectively reversed by BzATP (P2X7R activator). CONCLUSION: TMP alleviated SCI via reducing tissue damage, neuroinflammation, and the expression of P2X7R, NLRP3, IL-1ß, and IL-18.

Femoral neck system vs. cannulated screws on treating femoral neck fracture: a meta-analysis and system review.

Objective: This meta-analysis aimed to compare the relative safety and efficacy of cannulated compression screw (CCS) and femoral neck system (FNS) in treating patients with femoral neck fractures and to provide evidence-based medical evidence for FNS in treating femoral neck fractures. Methods: PubMed, Embase, Cochrane, and China National Knowledge Infrastructure databases were searched to collect outcomes related to femoral neck fractures treated with FNS and CCS, including time to fracture healing, incidence of non-union, incidence of osteonecrosis of the femoral head, incidence of failure of internal fixation, rate of femoral neck shortening, Harris hip score, Barthel index, operative time, intraoperative blood loss, fluoroscopy frequency, and complications. A meta-analysis was performed using RevManv5.4 (The Cochrane Collaboration) and Stata v14.0 software. Results: This analysis included 21 studies involving 1,347 patients. The results showed that FNS was superior to CCS in terms of fracture healing time [mean difference (MD) = -0.75, 95% CI = (-1.04, -0.46), P < 0.05], incidence of bone non-union [odds ratio (OR) = 0.53, 95% CI = (0.29, 0.98), P = 0.04], incidence of osteonecrosis of the femoral head [OR = 0.49, 95% CI = (0.28, 0.86), P = 0.01], incidence of internal fixation failure [OR = 0.30, 95% CI = (0.18, 0.52), P < 0.05], rate of femoral neck shortening [OR = 0.38, 95% CI = (0.27, 0.54), P > 0.05], Harris hip score [MD = 3.31, 95% CI = (1.99, 4.63), P < 0.001], Barthel index [MD = 4.31, 95% CI = (3.02, 5.61), P < 0.05], intraoperative bleeding [MD = 14.72, 95% CI = (8.52, 20.92), P < 0.05], fluoroscopy frequency [OR = 0.53, 95% CI = (0.29, 0.98), P = 0.04], and complications [OR = 0.31, 95% CI = (0.22, 0.45), P < 0.05]. The difference between FNS and CCS in operative time was not statistically significant [MD = -2.41, 95% CI = (-6.88, 2.05), P = 0.29]. Conclusion: FNS treatment of femoral neck fracture can shorten the fracture healing time; reduce the incidence and translucent rate of bone non-union, osteonecrosis of the femoral head, and internal fixation failure; reduce intraoperative blood loss and postoperative complications; and improve hip joint function and activity. We are confident in the findings that FNS, an effective and safe procedure for internal fixation of femoral neck fractures, is superior to CCS.

The reconstruction of fingertip injury by mini hallux toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique based on the equivalent design theory.

INTRODUCTION: How to reconstruct the damaged fingertip is a clinical problem. Our team propose the theory of equivalent design and use the mini toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique to reconstruct Allen's type II fingertip injury. Thus, we perform the retrospective study to evaluate the effects of this technique on fingertip injury. MATERIALS AND METHODS: A retrospective analysis was performed on 56 patients admitted to our hospital from January 2015 to January 2020 who used equivalently designed miniature hallux toenail flaps for the plastic repair of fingertip damage. We recorded the size of the miniature hallux toenail flap, operation time, intraoperative blood loss, and complications and calculated the survival rate of the transplanted miniature hallux toenail flap. During routine follow-up after surgery, we recorded nail growth time and observed finger appearance. At the last time of follow-up, we recorded Semmes-Weinstein evaluating tactile sensation and Two-point discrimination testing (TPD). The efficacy was evaluated by Zook score evaluation. RESULTS: The size of the mini hallux toenail flap was 0.71 cm × 1.22 cm to 0.88 cm × 1.71 cm. The operation time was (3.54 ± 0.58) hours, the intraoperative blood loss was (20.66 ± 4.87) ml, and the survival rate of mini hallux toenail flaps was 100%. The postoperative follow-up time was (30.82 ± 11.21) months, and the total nail growth time was (9.68 ± 2.11) months. The average tactile sensation evaluated by the Semmes-Weinstein test was (0.32 ± 0.14) g, and the average TPD was (7.33 ± 1.02) mm. According to Zook score, the curative effect of fifty-six cases were all excellent or good with 100% excellent and good rate, and all patients had beautiful appearances and good function of damaged fingertips. CONCLUSIONS: Based on the equivalent design theory, the mini hallux toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique is an effective method to reconstruct Allen's type II fingertip injury with a beautiful appearance and good function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Recent Progress in antibacterial hydrogel coatings for targeting biofilm to prevent orthopedic implant-associated infections.

The application of orthopedic implants for bone tissue reconstruction and functional restoration is crucial for patients with severe bone fractures and defects. However, the abiotic nature of orthopedic implants allows bacterial adhesion and colonization, leading to the formation of bacterial biofilms on the implant surface. This can result in implant failure and severe complications such as osteomyelitis and septic arthritis. The emergence of antibiotic-resistant bacteria and the limited efficacy of drugs against biofilms have increased the risk of orthopedic implant-associated infections (OIAI), necessitating the development of alternative therapeutics. In this regard, antibacterial hydrogels based on bacteria repelling, contact killing, drug delivery, or external assistance strategies have been extensively investigated for coating orthopedic implants through surface modification, offering a promising approach to target biofilm formation and prevent OIAI. This review provides an overview of recent advancements in the application of antibacterial hydrogel coatings for preventing OIAI by targeting biofilm formation. The topics covered include: (1) the mechanisms underlying OIAI occurrence and the role of biofilms in exacerbating OIAI development; (2) current strategies to impart anti-biofilm properties to hydrogel coatings and the mechanisms involved in treating OIAI. This article aims to summarize the progress in antibacterial hydrogel coatings for OIAI prevention, providing valuable insights and facilitating the development of prognostic markers for the design of effective antibacterial orthopedic implants.

Activation of the alpha 7 nicotinic acetylcholine receptor mitigates osteoarthritis progression by inhibiting NF-κB/NLRP3 inflammasome activation and enhancing autophagy.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degradation. Alpha 7 nicotinic acetylcholine receptor (α7nAChR) is associated with inflammatory and metabolic responses in OA. However, the mechanisms underlying the pathological process of OA remain unclear. The aim of the present study was to examine the role and mechanisms of α7nAChR-mediated autophagy and anti-inflammatory response in chondroprotection. Monosodium iodoacetate (MIA)-induced Wistar rat OA model was used to assess the in vivo effects of the ɑ7nAChR agonist (PNU-282987). The histopathological characteristics of OA were evaluated by immunohistochemistry (IHC), and the levels of autophagy markers were determined by western blotting and transmission electron microscopy. The anti-inflammatory effect of the ɑ7nAChR agonist was assessed by IHC, quantitative real-time polymerase chain reaction, and western blotting. Parallel experiments to determine the molecular mechanisms through which the ɑ7nAChR agonist prevents OA were performed using interleukin-1ß (IL-1ß)-treated chondrocytes. Our results showed that PNU-282987 reduced cartilage degeneration and matrix metalloproteinase (MMP)-1 and MMP-13 expressions. Activating α7nAChR with PNU-282987 significantly promoted MIA/IL-1ß-induced chondrocyte autophagy, as demonstrated by the increase in LC3-II/LC3-I ratio, Beclin-1 levels, and autophagosome number. Furthermore, treating chondrocyte with ULK1 siRNA attenuated the PNU282987-induced enhancement of LC3-II/LC3-I ratio and Beclin-1 level. Additionally, PNU282987 suppressed NF-κB/NLRP3 inflammasome activation by inhibiting the ROS/TXNIP pathway and suppressed tumor necrosis factor-ɑ and IL-1ß secretion in MIA/IL-1ß-treated chondrocytes. Our results demonstrate that the activation of α7nAChR promotes chondrocyte autophagy and attenuates inflammation to mitigate OA progression, providing a novel target for the treatment of OA.

A hybrid technique combining intramedullary pinning with extramedullary plate fixation in unstable and comminuted radial head fractures following on-table reconstruction.

BACKGROUND: Management of comminuted radial fractures remains controversial. Currently, the emergence of on-table reconstruction technique has made fixation in comminuted radial head fractures more viable. However, the present study reported an intro-operative unstable displacement from the reconstructed radial head to the neck during plate fixation, characterized by a poor radiocapitellar contact and incongruity between the radial head and neck. A hybrid technique combining with intramedullary pining was performed in our study to restore the normal alignment and maintain the stability of fixation. Therefore, the purpose of this article aimed to prove the feasibility of unstable comminuted radial head fractures treated with the extramedullary plate and intramedullary pinning fixation using titanium elastic nails. METHODS: The clinical, functional and radiographic outcomes of the groups were compared during follow-up. The radiographic examination was conducted to evaluate the status of bone union, heterotopic ossification and post-traumatic arthritis. The functional assessment was performed to evaluate clinical effects, which included measurements of range of motion (ROM) in the elbow, Visual Analog Scale (VAS) score, Elbow Self-Assessment score (ESAS), Mayo Elbow Performance score (MEPS), and Disabilities of the Arm, Shoulder, and Hand (DASH)Outcome Measure score. RESULTS: Thirteen patients with unstable fractures were participated with an average follow-up of (38.6 ± 4.5) months for the experimental group and (32.0 ± 6.3) months for the control group, respectively. The functional outcomes in the experimental group, including MEPS and DASH, were significantly superior to the control group. However, no significant difference was observed in the elbow ROM and VAS score between two groups. In the last follow-up, one patient with post-traumatic arthritis rated as grades 1 and two with heterotopic ossifications were observed in the experimental group. In the control group, degenerative changes were observed in three cases (grade 1 in two cases and grade 2 in one case) and heterotopic ossifications rated as grade I were found in two patients. CONCLUSION: Collectively, intramedullary pinning with extramedullary plate fixation is feasible in unstable comminuted radial head fractures, which can be considered as a remedial surgery for on-table reconstruction technique.

Double Bundle versus Single Bundle Reconstruction in the Treatment of Posterior Cruciate Ligament Injury: A Prospective Comparative Study.

BACKGROUND: The debate continues regarding the best way to reconstruct posterior cruciate ligament (PCL). The objective of this study was to compare the knee stability and clinical outcomes after single and double bundle (SB and DB) PCL reconstruction. MATERIALS AND METHODS: A total of 98 patients with PCL injury were enrolled for PCL reconstruction with four-strand semitendinosus and gracilis tendon autograft in the SB technique (n = 65) or two-strand Achilles allograft in the DB technique (n = 33). Each bundle fixation was achieved by the means of femoral Endo Button CL and tibial bioabsorbable interference screw. Demographic data, knee stability, and clinical outcomes were collected for analysis. RESULTS: The SB and DB groups showed comparable demographic data. After a minimum followup interval of 24 months, the data of 59 patients in the SB group and 30 patients in the DB group were analyzed. There was no statistical difference between the SB and DB group in terms of both knee stability and clinical outcomes (P > 0.05). CONCLUSIONS: Compared with the SB technique, the DB technique did not exhibit any superiority in knee stability or clinical outcomes.

Nitidine chloride suppresses epithelial-to-mesenchymal transition in osteosarcoma cell migration and invasion through Akt/GSK-3ß/Snail signaling pathway.

Metastasis is the main cause of death in osteosarcoma. Targeting the process of metastasis is a main strategy for osteosarcoma therapy. As a traditional Chinese medicine, Zanthoxylum nitidum (Roxb) has been applied to treat various diseases, including cancer. However, no evidence has been shown on the anti-metastasis effect of nitidine chloride (NC) that was extracted from Zanthoxylum nitidum (Roxb) on osteosarcoma cells, or its underling mechanisms. In the present study, we aimed to demonstrate the role of NC on the migration and invasion of osteosarcoma cells. Viability and proliferation of osteosarcoma cells were examined by MTT assay. Then, by appling scratch wound healing assay and Transwell assays, we evaluated migratory and invasive ability of the cells, respectively. Moreover, the expression of epithelial-to-mesenchymal transition (EMT) markers were determined after treatment with NC. Furthermore, the expression of Akt, GSK-3ß and Snail were detected by western blot analysis. In addition, the GSK-3ß activity was examined by GSK-3ß kinase assay. Finally, an inhibitor of GSK-3ß, lithium chloride (LiCl) was applied to testify the effect of NC on the expression of EMT markers and Snail. We found that the proliferative, migratory and invasive ability of the U2OS osteosarcoma cells were all suppressed when treated with NC. NC increased the expression of E-cadherin and decreased the expression of N-cadherin, vimentin and fibronectin in a dose-dependent manner. NC also exerted its ability to suppress the phosphorylation of Akt and GSK-3ß so as to activate GSK-3ß. Then, by using an GSK-3ß inhibitor, LiCl, we revealed the effect of GSK-3ß in the expression of EMT markers. The expression of Snail was inhibited when treated with NC and LiCl also reversed the NC-inhibited Snail expression. Taken together, these results revealed that NC suppressed EMT and decreased the invasive ability of osteosarcoma cells via the Akt/GSK-3ß/snail signaling pathway.

[Arthroscopic treatment for post-traumatic chronic wrist pain].

OBJECTIVE: To explore the therapeutic effects of arthroscopy for post-traumatic chronic wrist pain. METHODS: From February 2007 to June 2010, 12 patients with post-traumatic chronic wrist pain treated with arthroscopy were reviewed. Among the patients, 9 patients were male and 3 patients were female, ranging in age from 19 to 47 years, with a mean of 35.6 years. After physical examinations or MR abnormal findings, all the patients underwent wrist arthroscopic examination and treatment. Eight patients with tear in the central area of the triangular fibrocartilage complex (TFCC) underwent endoscopic partial resection. Two patients with relaxation of inter-carpal ligament after injury underwent radiofrequency shrinkage. One patient with distal radioulnar joint instability was treated with Kirschner fixation through distal radius and ulna in the neutral forearm rotation after clean-up of wrist joint, and also fixed with long arm cast immobilization for 6 weeks. One patient with ulnar impaction syndrome was treated with wrist clean, border modeling of triangular cartilage plate, partial resection of distal ulna. RESULTS: All the patients were followed up with an average duration of 10 months. Modified Mayo wrist score were evaluated from preoperative mean of (51.67 +/- 15.27) ( 25 to 75 scores) to postoperative mean of (77.92 +/- 10.54) (65 to 95 scores). Eleven patients recovered to normal work. CONCLUSION: Arthroscopy is an effective method for patients with post-traumatic chronic wrist pain which can diagnosis and cure the injuries under arthroscopy.