Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment.

BACKGROUND AND AIMS: Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of joint cartilage, synovial inflammation, and subchondral bone hyperplasia. The synovial tissue plays a pivotal role in cartilage regulation. Exosomes (EXOs), small membrane-bound vesicles released by cells into the extracellular space, are crucial in mediating intercellular communication and facilitating the exchange of information between tissues. Our study aimed to devise a hydrogel microsphere infused with SOD3-enriched exosomes (S-EXOs) to protect cartilage and introduce a novel, effective approach for OA treatment. MATERIALS AND METHODS: We analyzed single-cell sequencing data from 4247 cells obtained from the GEO database. Techniques such as PCR, Western Blot, immunofluorescence (IF), and assays to measure oxidative stress levels were employed to validate the cartilage-protective properties of the identified key protein, SOD3. In vivo, OA mice received intra-articular injections of S-EXOs bearing hydrogel microspheres, and the effectiveness was assessed using safranine O (S.O) staining and IF. RESULTS: Single-cell sequencing data analysis suggested that the synovium influences cartilage via the exocrine release of SOD3. Our findings revealed that purified S-EXOs enhanced antioxidant capacity of chondrocytes, and maintained extracellular matrix metabolism stability. The S-EXO group showed a significant reduction in mitoROS and ROS levels by 164.2% (P < 0.0001) and 142.7% (P < 0.0001), respectively, compared to the IL-1ß group. Furthermore, the S-EXO group exhibited increased COL II and ACAN levels, with increments of 2.1-fold (P < 0.0001) and 3.1-fold (P < 0.0001), respectively, over the IL-1ß group. Additionally, the S-EXO group showed a decrease in MMP13 and ADAMTS5 protein expression by 42.3% (P < 0.0001) and 44.4% (P < 0.0001), respectively. It was found that S-EXO-containing hydrogel microspheres could effectively deliver SOD3 to cartilage and significantly mitigate OA progression. The OARSI score in the S-EXO microsphere group markedly decreased (P < 0.0001) compared to the OA group. CONCLUSION: The study demonstrated that the S-EXOs secreted by synovial fibroblasts exert a protective effect on chondrocytes, and microspheres laden with S-EXOs offer a promising therapeutic alternative for OA treatment.

Antibiotic-loaded calcium sulfate beads in spinal surgery for patients with spondylodiscitis: a clinical retrospective study.

BACKGROUND: Various surgical techniques for treating spondylodiscitis have been proposed, but the optimal surgical treatment remains controversial. In this study, we propose a new procedure that is implanting antibiotic-loaded calcium sulfate (CS) beads into the disc after debridement using the Quadrant channel combined with percutaneous fixation through a single-stage posterolateral approach for the treatment of spondylodiscitis. Thus, the purpose of this study is to assess the safety and efficacy of this procedure. METHODS: This study collected the data of 32 patients with spine spondylodiscitis and was surgically treated in our department from July 2015 to August 2020. The Demographic data included age, gender, involved segment, and complications were collected. The intra-operative details, results of culture, functional outcome, radiologic outcome, and length of hospital stay, laboratory examination were recorded. RESULTS: The mean age of the 32 patients was 61.1 ± 9.7 years old. The mean operative time was 135.0 ± 30.6 minutes, and the mean blood loss was 243.4 ± 92.1 ml. The positive rate of culture was 72%. The mean Visual analogue scale (VAS) and Oswestry Disability Index (ODI) score significantly improved from 7.5 to 1.6 and from 65% to 10%. Cobb angle was significantly improved and could be maintained at final follow-up. New bone formation was observed in all patients. There were no recurrences of infection in our study. CONCLUSIONS: The posterolateral debridement and percutaneous fixation combined with antibiotic-loaded calcium sulfate beads filling are effective in the treatment of spondylodiscitis in terms of infection control, early mobilization, and recovery.

Estrogen-Related Receptor α: A Significant Regulator and Promising Target in Bone Homeostasis and Bone Metastasis.

Bone homeostasis is maintained with the balance between bone formation and bone resorption, which is involved in the functional performance of osteoblast and osteoclast. Disruption of this equilibrium usually causes bone disorders including osteoporosis, osteoarthritis, and osteosclerosis. In addition, aberrant activity of bone also contributes to the bone metastasis that frequently occurs in the late stage of aggressive cancers. Orphan nuclear receptor estrogen-related receptor (ERRα) has been demonstrated to control the bone cell fate and the progression of tumor cells in bone through crosstalk with various molecules and signaling pathways. However, the defined function of this receptor in bone is inconsistent and controversial. Therefore, we summarized the latest research and conducted an overview to reveal the regulatory effect of ERRα on bone homeostasis and bone metastasis, this review may broaden the present understanding of the cellular and molecular model of ERRα and highlight its potential implication in clinical therapy.

Microscopic extra-laminar sequestrectomy (MELS) for the treatment of hidden zone lumbar disc herniation: report of the surgical technique, patient selection, and clinical outcomes.

BACKGROUND: The area which located at the medial pedicle, posterior vertebral body and ventral hemilamina is defined as the hidden zone. Surgical management of hidden zone lumbar disc herniation (HZLDH) is technically challenging due to its difficult surgical exposure. The conventional interlaminar approach harbors the potential risk of post-surgical instability, while other approaches consist of complicated procedures with a steep learning curve and prolonged operation time. OBJECTIVE: To introduce microscopic extra-laminar sequestrectomy (MELS) technique for treatment of hidden zone lumbar disc herniation and present clinical outcomes. METHODS: Between Jan 2016 to Jan 2018, twenty one patients (13 males) with HZLDH were enrolled in this study. All patients underwent MELS (19 patients underwent sequestrectomy only, 2 patients underwent an additional inferior discectomy). The nerve root and fragment were visually exposed using MELS. The operation duration, blood loss, intra- and postoperative complications, and recurrences were recorded. The Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and the modified MacNab criteria were used to evaluate clinical outcomes. Postoperative stability was evaluated both radiologically and clinically. RESULTS: The mean follow-up period was 20.95 ± 2.09 (18-24) months. The mean operation time was 32.43 ± 7.19 min and the mean blood loss was 25.52 ± 5.37 ml. All patients showed complete neurological symptom relief after surgery. The VAS and ODI score were significantly improved at the final follow-up compared to those before operation (7.88 ± 0.70 vs 0.10 ± 0.30, 59.24 ± 10.83 vs 11.29 ± 3.59, respectively, p < 0.05). Seventeen patients (81%) obtained an "excellent" outcome and the remaining four (19%) patients obtained a "good" outcome based the MacNab criteria. One patient suffered reherniation at the same level one year after the initial surgery and underwent a transforaminal endoscopic discectomy. No major complications and postoperative instability were observed. CONCLUSIONS: Our observation suggest that MELS is safe and effective in the management of HZLDH. Due to its relative simplicity, it comprises a flat surgical learning curve and shorter operation duration, and overall results in reduced disturbance to lumbar stability.

Finely Tuned Porous Coordination Polymers To Boost Methane Separation Efficiency.

Absorbents with high breakthrough efficiency and weak host-guest interaction are considered to be promising candidates for an energy-saving process in feasible pressure/volume swing adsorption (PSA/VSA). Herein, two groups of finely designed Fe- and Co-based porous coordination polymers (PCPs) are proposed and validated; these possess hourglass-shaped nanochannels, through the cooperation of T-shaped ligands with shifted methyl groups. Featuring optimal nanochannels, high static adsorption, and relatively lower binding energy, one of these polymers, named NTU-30, enables significant C2 H6 /CH4 and C2 H4 /CH4 breakthrough efficiency, with approximately 1.0 or 0.6 g CH4 (100 %) harvested from the corresponding mixtures using 1 g of sample at ambient temperature. Furthermore, the positive effect of aromatic sites within NTU-30 is detected and investigated through an in situ IR study.

Finely Controlled Stepwise Engineering of Pore Environments and Mechanistic Elucidation of Water-Stable, Flexible 2D Porous Coordination Polymers.

Two porous coordination polymers (PCPs) with different topologies (NTU-19: sql and NTU-20: dia) underwent finely controlled, stepwise crystal conversions to yield a common water-stable, flexible 2D framework (NTU-22: kgm). The crystal conversions occurred directly at higher temperature via the 3D intermediate (NTU-21: nbo), which could be observed at lower temperature. The successful isolation of the intermediate product of NTU-21, characterization with in situ PXRD and UV/Vis spectra were combined with DFT calculations to allow an understanding of the dynamic processes at the atomic level. Remarkably, breakthrough experiments demonstrate NTU-22 with integral structural properties allowed significant CO2 /CH4 mixture separation.

A Free Tetrazolyl Decorated Metal-Organic Framework Exhibiting High and Selective CO2 Adsorption.

In this work, we employed a new tetrazolyl-functionalized ligand, 5-(1H-tetrazole-5-yl)-1,3-bis(3,5-dicarboxylphenyl)-benzene (H5TBDPB), and successfully obtained an example of incorporating free tetrazolyl groups in transition-metal-based MOFs based upon an ideal MOF platform. With a BET surface area of 2070 m2 g-1, this new tetrazolyl-decorated MOF [Cu6(TBDPB)3(H2O)6]·9DMF·15H2O (HHU-5, HHU for Hohai University) exhibits a high CO2 adsorption capacity of 37.1 wt % at 1 bar and 273 K and high CO2 separation capacity toward N2 and CH4 as well.

Cascaded controlled delivering growth factors to build vascularized and osteogenic microenvironment for bone regeneration.

The process of bone regeneration is intricately regulated by various cytokines at distinct stages. The establishment of early and efficient vascularization, along with the maintenance of a sustained osteoinductive microenvironment, plays a crucial role in the successful utilization of bone repair materials. This study aimed to develop a composite hydrogel that would facilitate the creation of an osteogenic microenvironment for bone repair. This was achieved by incorporating an early rapid release of VEGF and a sustained slow release of BMP-2. Herein, the Schiff base was formed between VEGF and the composite hydrogel, and VEGF could be rapidly released to promote vascularization in response to the early acidic bone injury microenvironment. Furthermore, the encapsulation of BMP-2 within mesoporous silica nanoparticles enabled a controlled and sustained release, thereby facilitating the process of bone repair. Our developed composite hydrogel released more than 80% of VEGF and BMP-2 in the acidic medium, which was significantly higher than that in the neutral medium (about 60%). Moreover, the composite hydrogel demonstrated a significant improvement in the migratory capacity and tube formation ability of human umbilical vein endothelial cells (HUVECs). Furthermore, the composite hydrogel exhibited an augmented ability for osteogenesis, as confirmed by the utilization of ALP staining, alizarin red staining, and the upregulation of osteogenesis-related genes. Notably, the composite hydrogel displayed substantial osteoinductive properties, compared with other groups, the skull defect in the composite hydrogels combined with BMP-2 and VEGF was full of new bone, basically completely repaired, and the BV/TV value was greater than 80%. The outcomes of animal experiments demonstrated that the composite hydrogel effectively promoted bone regeneration in cranial defects of rats by leveraging the synergistic effect of an early rapid release of VEGF and a sustained slow release of BMP-2, thereby facilitating vascularized bone regeneration. In conclusion, our composite hydrogel has demonstrated promising potential for vascularized bone repair through the enhancement of angiogenesis and osteogenic microenvironment.

Number of positive lymph nodes is superior to neck stage of the 8th AJCC in predicting prognosis in parotid mucoepidermoid carcinoma.

BACKGROUND: To clarify the impact of the number of positive lymph nodes (LNs) on the prognosis of parotid mucoepidermoid carcinoma (MEC). METHODS: Patients who underwent neck dissection for parotid MEC were retrospectively enrolled. The primary outcome variable was overall survival (OS). Associations between OS and LN factors, including the AJCC N stage, intraparotid LN metastasis, number of positive LNs, LN size, and extranodal extension (ENE), were evaluated using Cox proportional hazard regression analyses. RESULTS: A total of 720 patients were included with a mean age of 56 ± 16 years. There was no additional survival compromise until two positive LNs were presented. After adjusting for the number of positive LNs, intraparotid LN metastasis, ENE, and LN size were not related to prognosis. Our proposed N stage based on the number of metastatic LNs (0/1 vs. 2-4 vs. 5+) showed a superior C-index to the AJCC N stage in OS prediction. CONCLUSION: Quantitative LN burden was an important determinant of prognosis, and the proposed N stage provided better OS stratification than the AJCC N stage.

Anterior cervical plating combined with zero-profile anchored spacer for the treatment of cervical facet dislocation in elderly patients.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of anterior cervical plating combined with zero-profile (Z-P) anchored spacer for the treatment of cervical facet dislocation in elderly patients. METHODS: This is a retrospective study. Twelve elderly patients (from 57 to 77 years old, averaged 65 years) with unilateral or bilateral facet dislocation of sub-axial cervical spine from September 2015 to September 2019 surgically treated at the authors' hospital were enrolled in this study. The patients with osteoporosis or osteopenia were all surgically treated by anterior-only procedure using cervical plating combined with zero-profile anchored spacer after closed manual reduction under general anesthesia and spinal cord monitoring. The operation times (OT), estimated blood loss (EBL), perioperative complications, were recorded. The clinical evaluation included visual analogue scales (VAS) and the American Spinal Injury Association (ASIA) scale. The radiographic evaluation included kyphotic angle (KA) and disc height (DH) and the fusion rate. RESULTS: Anterior discectomy, interbody fusion and fixation were performed in all patients after the disloctions were reduced by manual maneuver. The average OT was 66 minutes, with a range from 45 to 110 minutes. The EBL averaged 42 ml per surgical procedure, with a range from 20 to 60 ml. The VAS, ASIA, KA were improved significantly after surgery (P<0.05). The average follow-up time was 24.2 months, with a range from 12 to 38 months. There were no statistical differences between the immediately post-op KA and KA at the last follow-up (P>0.05). No disc space subsidence was observed statistically (P<0.05) Interbody fusion was obtained in all patients. Two patient experienced slight difficulty in swallowing, which were improved 6 weeks later. There were no hardware failure, no segmental instability, no wound infection or other complications. CONCLUSIONS: Manual reduction with spinal cord monitoring under general anesthesia is a safe and efficient option and the anterior cervical plating combined with Z-P spacer could achieve reliable fixation for the patients with cervical facet dislocation in the elderly patients with osteoporosis or osteopenia.

Accelerated C2H2/CO2 Separation by a Se-Functionalized Porous Coordination Polymer with Low Binding Energy.

High-quality pure acetylene (C2H2) is a kind of crucial starting material for various value-added products. However, selective capture of C2H2 from the main impurity of CO2 via porous absorbents is a great challenge, as they possess extremely similar kinetic diameters and boiling points, as well as the explosive and reactive properties of C2H2. Herein, we report a porous coordination polymer (PCP), (NTU-55), which assembled from the coordination between a Cu dimer and a newly designed ligand with a nonmetal selenium (Se) site. Static single-component adsorption and dynamic breakthrough experiments reveal that desolvated NTU-55 can completely adsorb C2H2 from the C2H2/CO2 mixture (1/4, v/v) at 298 K, along with higher C2H2 capacity and much lower binding energy. The origin of this separation, as comprehensively revealed by density functional theory (DFT) calculations, is derived from the interaction discriminatory of C2H2 and CO2 toward accessible Se and Cu adsorption sites. To the best of our knowledge, this is the first time to find the positive effect of nonmetal Se sites for selective C2H2 capture.

Minimally invasive far lateral debridement combined with posterior instrumentation for thoracic and lumbar tuberculosis without severe kyphosis.

BACKGROUND: Anti-tuberculous therapy (ATT) alone cannot easily cure spine tuberculosis (STB) though it is the most essential treatment. Many studies have confirmed the efficacy of the surgical treatment of STB through anterior, anterolateral, posterior debridement, and intervertebral fusion or combined with internal fixation. However, the conventional surgical approach requires extensive exposure of the affected areas with high rates of morbidity and mortality. Recently, minimally invasive surgery has come into use to reduce iatrogenic trauma and relevant complications. Here, we introduced a novel technique for the treatment of thoracic and lumbar spine tuberculosis: minimally invasive far lateral debridement and posterior instrumentation (MI-FLDPI). In this study, we evaluated the technical feasibility, the clinical outcomes, and the postoperative complications. METHODS: We did a prospective, non-randomized study on this new technique. Twenty three patients (13 males) with thoracic or lumbar spine tuberculosis who underwent minimally invasive far lateral debridement and posterior instrumentation were included in the study. The preoperative comorbidities, operation duration, intra-operative hemorrhage, Cobb's angles, and postoperative complications were recorded and analyzed. Clinical outcomes were evaluated by Visual Analog Scale (VAS), Oswestry Disability Index (ODI), neurological recovery, and eradication of tuberculosis. Radiological outcomes were evaluated by changes in Cobb's angle and fusion status of the affected segments. RESULTS: The patients were followed for an average of 19 months (ranging from 12 to 36 months). At the final follow-up, CRP and ESR of all patients were normal. The VAS and ODI were significantly improved compared with preoperative values (P < 0.05). No evident progression of the kyphotic deformity was found after surgery. Twenty two patients showed spontaneous peripheral interbody fusion 1 year after surgery. There were no failure of the instrumentation even though a young female with drug-resistant tuberculosis showed no sign of interbody fusion at the third year follow-up. All the patients with preoperative neurological deficit showed complete recovery at the final follow-up. CONCLUSIONS: MI-FLDPI using expandable tubular retractor could be recommended to treat thoracic and lumbar spine tuberculosis for the advantages of less trauma, earlier recovery, and less complications. Spontaneous peripheral interbody fusion was observed in nearly all the cases even without bone grafting.

Enhanced Breakthrough Efficiency by a Chemically Stable Porous Coordination Polymer with Optimized Nanochannel.

High separation efficiency is very important for process of pressure swing adsorption (PSA) in the industry. Herein, we propose a fine design of chemically stable porous coordination polymers (PCPs) with optimized nanochannel by strategy of inserting and shifting shortest alkyl group on T-shaped ligand. Remarkably, the synergistic effect of optimized nanochannel, unique crystal morphology and fitted channel enable sharply enhanced breakthrough efficiency of C2H6/4/CH4, 1.17 or 0.77 g of CH4 can be separated from corresponding dual mixtures (2/8, v/v) by 1 g of NTU-25 at 273 K, which was further validated and understood by controlled experiments and density functional theory (DFT) computations.