New perspectives on YTHDF2 O-GlcNAc modification in the pathogenesis of intervertebral disc degeneration.

This study investigates the potential molecular mechanisms by which O-GlcNAc modification of YTHDF2 regulates the cell cycle and participates in intervertebral disc degeneration (IDD). We employed transcriptome sequencing to identify genes involved in IDD and utilized bioinformatics analysis to predict key disease-related genes. In vitro mechanistic validation was performed using mouse nucleus pulposus (NP) cells. Changes in reactive oxygen species (ROS) and cell cycle were assessed through flow cytometry and CCK-8 assays. An IDD mouse model was also established for in vivo mechanistic validation, with changes in IDD severity measured using X-rays and immunohistochemical staining. Bioinformatics analysis revealed differential expression of YTHDF2 in NP cells of normal and IDD mice, suggesting its potential as a diagnostic gene for IDD. In vitro cell experiments demonstrated that YTHDF2 expression and O-GlcNAcylation were reduced in NP cells under H2O2 induction, leading to inhibition of the cell cycle through decreased stability of CCNE1 mRNA. Further, in vivo animal experiments confirmed a decrease in YTHDF2 expression and O-GlcNAcylation in IDD mice, while overexpression or increased O-GlcNAcylation of YTHDF2 promoted CCNE1 protein expression, thereby alleviating IDD pathology. YTHDF2 inhibits its degradation through O-GlcNAc modification, promoting the stability of CCNE1 mRNA and the cell cycle to prevent IDD formation.

Three-dimensional-printed MPBI@ß-TCP scaffold promotes bone regeneration and impedes osteosarcoma under near-infrared laser irradiation.

Beta-tricalcium phosphate (ß-TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study generated a functional molybdenum disulfide (MoS2 )/polydopamine (PDA)/-bone morphogenetic protein 2 (BMP2)-insulin-like growth factor-1 (IGF-1) coating on the ß-TCP scaffold and analyzed the outcomes. The MoS2 /PDA-BMP2-IGF-1@ß-TCP (MPBI@ß-TCP) scaffold was prepared by 3D printing and physical adsorption, followed by characterization to validate its successful construction. The in vitro osteogenic effect of the MPBI@ß-TCP scaffold was evaluated. It was found that MPBI@ß-TCP augmented the adhesion, diffusion and proliferation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity, collagen secretion and extracellular matrix (ECM) mineralization along with the expression of Runx2, ALP and OCN were also enhanced in the presence of MPBI@ß-TCP. Additionally, MPBI@ß-TCP stimulated endothelial cells to secrete VEGF and promoted capillary-like tubule formation. We then confirmed the biocompatibility of MPBI@ß-TCP to macrophages and its anti-inflammatory effects. Furthermore, under near-infrared (NIR) laser irradiation, MPBI@ß-TCP produced photothermal effect to not only kill MG-63 osteosarcoma cells, but also enhance bone regeneration in vivo with biosafety. Overall, this work demonstrates that 3D-printed MPBI@ß-TCP with enhanced osteogenic activity under NIR laser irradiation has a vast potential in the field of tissue defects.

Dynamic Fixation Versus Static Fixation for Distal Tibiofibular Syndesmosis Injuries: A Meta-Analysis.

BACKGROUND Ankle sprains with distal tibiofibular syndesmosis injuries (DTSIs) require anatomic reduction and fixation to restore the normal biomechanics of the ankle joint. In the last decade, dynamic fixation (DF) for DTSIs using a suture-button device has gained popularity because of its advantages over static fixation (SF). MATERIAL AND METHODS The present meta-analysis was conducted to compare clinical outcomes between DF and SF of DTSIs. PubMed, Cochrane Central Register of Controlled Trials, and Embase were systematically searched. Three randomized controlled studies and 7 cohort studies, with a total of 420 patients, were involved in this study. DTSIs patients treated with DF were assigned to the experimental group, and patients treated with SF were assigned to the control group. Outcomes were evaluated and analyzed by using review-manager software. Mean difference (MD) or risk ratio (RR) with 95% confidence interval (95% CI) was analyzed and calculated by utilizing the random effects models. RESULTS Analysis revealed no statistically significant differences between DF and SF in American Orthopedic Foot and Ankle Society Ankle-Hindfoot score (MD, 1.90; 95% CI, -0.23-4.03; p=0.08; I²=0%), Olerud-Molander score (MD, 1.92; 95% CI, -7.96-11.81; p=0.70; I²=55%), incidence of syndesmotic malreduction (RR, 0.19; 95% CI, 0.03-1.09; p=0.06; I²=0%), and overall postoperative complication rate (RR, 0.30; 95% CI, 0.09-0.99; p=0.05, I²=75%). The rate of second procedure was significantly lower compared with DF (RR, 0.17; 95% CI, 0.07-0.43; p=0.0002, I²=54%). CONCLUSIONS The dynamic fixation and static fixation methods are equal in clinical outcomes, with dynamic fixation needing fewer second interventions for DTSIs.

Anterior transpedicular screws in conjunction with plate fixation and fusion for the treatment of subaxial cervical spine diseases.

OBJECTIVE: This study aimed at exploring the clinical application of anterior transpedicular screw (ATPS) and plate in the reconstruction of subaxial cervical spine. METHODS: 8 cases were reconstructed by ATPS and plate in the subaxial cervical spine from Jan 2009 to Dec 2011. X-rays and computed tomography images were collected to evaluate the position of ATPS. Magnetic resonance imaging was also included to evaluate the result of decompression, the existence of epidural hematoma and the morphology of the cervical spinal cord. Japanese Orthopaedic Association scores were observed before and after operation as a functional estimation. RESULTS: All of the eight cases were followed up from 3 to 36 months with the average of 15.5 months. A total of 16 ATPS were implanted in the subaxial cervical spine in the eight patients. All the screws were inserted smoothly. Bone fusion was found in all the subjects 4.5 months after operation on average. No loosening or breakage of the internal fixation was observed in our study. Hoarseness was observed in one case due to distraction injury of the recurrent laryngeal nerve, which disappeared after 3 weeks' conservative treatment. Dysphagia was complained by two patients after surgery, which was alleviated 3 months later. There were four screws deviating less than 1 mm (Grade 1), two medially and two laterally. All the anterior compressions were removed completely in this group. Only a small amount of epidural hematoma was found in four cases on MRI images before discharge. The average JOA scores were significantly improved from 5.6 ± 1.4 before surgery to 14.5 ± 0.8 at discharge (P < 0.01), which decreased to 13.2 ± 1.2 at 3 months after operation, but improved again to 15.2 ± 0.8 at 1 year after operation. CONCLUSION: Although there are some complications, ATPS with plate is an effective and safe technique for anterior reconstruction in the subaxial cervical spine. Only those spine centers with sufficient experience in complex cervical spine reconstruction surgery can conduct this technique according to strict indications.

Deep Learning Model for Automatic Identification and Classification of Distal Radius Fracture.

Distal radius fracture (DRF) is one of the most common types of wrist fractures. We aimed to construct a model for the automatic segmentation of wrist radiographs using a deep learning approach and further perform automatic identification and classification of DRF. A total of 2240 participants with anteroposterior wrist radiographs from one hospital between January 2015 and October 2021 were included. The outcomes were automatic segmentation of wrist radiographs, identification of DRF, and classification of DRF (type A, type B, type C). The Unet model and Fast-RCNN model were used for automatic segmentation. The DenseNet121 model and ResNet50 model were applied to DRF identification of DRF. The DenseNet121 model, ResNet50 model, VGG-19 model, and InceptionV3 model were used for DRF classification. The area under the curve (AUC) with 95% confidence interval (CI), accuracy, precision, and F1-score was utilized to assess the effectiveness of the identification and classification models. Of these 2240 participants, 1440 (64.3%) had DRF, of which 701 (48.7%) were type A, 278 (19.3%) were type B, and 461 (32.0%) were type C. Both the Unet model and the Fast-RCNN model showed good segmentation of wrist radiographs. For DRF identification, the AUCs of the DenseNet121 model and the ResNet50 model in the testing set were 0.941 (95%CI: 0.926-0.965) and 0.936 (95%CI: 0.913-0.955), respectively. The AUCs of the DenseNet121 model (testing set) for classification type A, type B, and type C were 0.96, 0.96, and 0.96, respectively. The DenseNet121 model may provide clinicians with a tool for interpreting wrist radiographs.

MicroRNA Let-7i Regulates Innate TLR4 Pathways in Peripheral Blood Mononuclear Cells of Patients with Ankylosing Spondylitis.

Purpose: This study aimed to compare the changes in the expression of microRNA Let-7i in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and the correlation between Let-7i and innate pro-inflammatory factors. It is necessary to search for a new biomarker to guide the prognosis of AS. Methods: A total of 10 patients with AS and 10 healthy volunteers were selected as AS and control groups, respectively. The expression levels of Let-7i, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and interferon-gamma (IFN-γ) in PBMCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) to explore the relationship between Let-7i and pro-inflammatory factors. Furthermore, the relationship between Let-7i and TLR4 was determined by the luciferase reporter technology. Results: The expression level of Let-7i in PBMCs of patients with AS was significantly lower than that of healthy control. The expression levels of TLR4, NF-κB, and IFN-γ in PBMCs derived from patients with AS were significantly higher than those of healthy control. The results show that Let-7i manipulation can regulate lipopolysaccharide (LPS)-induced TLR4 and IFN-γ expression in CD4+ T cells of patients with AS. The overexpression of Let-7i in T cells of patients with AS can suppress TLR4 and IFN-γ LPS-induced expression levels of cellular mRNA and protein. Let-7i can directly interfere TLR4-3'untranslated region (UTR) sequence and regulate the expression of the TLR4 gene in Jurkat T cells. Conclusion: Let-7i may be involved in the pathogenesis of AS, and Let-7i expression in PBMCs may be helpful for the diagnosis and treatment of AS in the future.

DNMT3a promotes osteoblast differentiation and alleviates osteoporosis via the PPARγ/SCD1/GLUT1 axis.

Background: This study was designed to elucidate the role of DNMT3a and PPARγ functions in postmenopausal osteoporosis. Materials & methods: Mice were ovariectomized to establish an in vivo osteoporosis model and MC3T3-E1-14 osteoblasts were induced to differentiate. Gain- or loss-of-function approaches were used to manipulate the expression of PPARγ, DNMT3a and SCD1, followed by an evaluation of their role in postmenopausal osteoporosis both in vivo and in vitro. Results: DNMT3a induced methylation of the PPARγ promoter region, consequently stimulating osteoblast differentiation. PPARγ elevated SCD1, which decreased GLUT1 and inhibited osteoblast differentiation. Inhibition of PPARγ reduced SCD1 while increasing GLUT1 expression, thus alleviating postmenopausal osteoporosis in mice. Conclusion: DNMT3a promotes osteoblast differentiation and prevents postmenopausal osteoporosis by regulating the PPARγ/SCD1/GLUT1 axis.

Positive feedback loop of lncRNA FAM201A/miR­146a­5p/POU2F1 regulates IL­1ß­induced chondrocyte injury in vitro.

Numerous studies have previously demonstrated that long non­coding RNAs (lncRNAs) serve an important regulatory role in osteoarthritis (OA). In particular, the lncRNA family with sequence similarity 201 member A (FAM201A) was previously found to be downregulated in necrotic femoral head samples. However, the role of FAM201A in IL­1ß­induced chondrocyte injury remains unclear. It was hypothesized that FAM201A may exert a protective effect on IL­1ß­induced chondrocyte injury in OA by sponging microRNAs (miRNAs/miRs). The purpose of the present study was to explore the role and molecular mechanism of FAM201A in IL­1ß­induced chondrocyte injury. A model of OA was established by stimulation C­28/I2 cell with IL­1ß in vitro. The expression levels of FAM201A following IL­1ß­induced chondrocyte injury were detected via reverse transcription­quantitative PCR. Luciferase reporter assay was used to assess the possible associations among FAM201A, miR­146a­5p and POU class 2 homeobox 1 (POU2F1). Chromatin immunoprecipitation assay was performed to analyze the interaction between POU2F1 and miR­146a­5p. ELISA, TUNEL and western blotting were performed to measure the level of inflammation, lactate dehydrogenase release, apoptosis and the expression of apoptosis­related proteins (Bcl­2, Bax, cleaved caspase 3 and cleaved caspase 9), respectively. The expression levels of FAM201A were found to be downregulated following IL­1ß­induced chondrocyte injury. Overexpression of FAM201A exerted a protective effect against IL­1ß­induced chondrocyte injury. In addition, FAM201A could upregulate the expression levels of POU2F1 by sponging miR­146a­5p. Further experiments revealed that POU2F1 could bind to the promoter region of FAM201A and subsequently regulate the expression levels of POU2F1, indicating a role for the FAM201A/miR­146a­5p/POU2F1 positive feedback loop in IL­1ß­induced chondrocyte injury. The present study revealed the protective effects of the FAM201A/miR­146a­5p/POU2F1 positive feedback loop on IL­1ß­induced chondrocyte injury and provided a potential therapeutic target for OA.

[Intraoperative IPC combined with 3M warming instrument to prevent lower extremity deep venous thrombosis in patients undergoing proximal femoral anti rotation intramedullary nailing].

OBJECTIVE: To explore the effect of intermittent pneumatic compression(IPC) combined with 3M thermometer on the prevention of deep venous thrombosis(DVT) in patients with femoral intertrochanteric fracture. METHODS: From March 2016 to August 2019, 127 patients with femoral intertrochanteric fractures who underwent proximal femoral nail antirotation(PFNA) were retrospectively analyzed. They were divided into two groups according to different methods of thrombus prevention and treatment. Among them, 63 patients in group A did not use IPC and 3M thermometer;64 cases in group B were treated with IPC combined with 3M thermometer. Color Doppler ultrasound was used to dynamically monitor the DVT and changes of lower limbs during perioperative period. The venous thrombosis of lower limbs was monitored at 0, 24, 72 h and > 72 h after operation(recheck every 3 days until discharge). RESULTS: Occurrence of DVT of lower limbs after PFNA operation in two groups:there were 5 cases (7.8%) in group B and 20 cases (31.7%) in group A, there was significant difference between two groups (P=0.001). There was no significant difference in lower limb DVT between two groups at 0, 72 and > 72 h after operation(P>0.05), but the formation rate of group A was significantly higher than that of group B at 24 h after operation (P=0.049). There was no significant difference in DVT formation between group A and group B(P>0.05). However, the formation of DVT in group A was significantly higher than that in group B(P=0.012). CONCLUSION: Intraoperative IPC combined with 3M thermostat can effectively prevent DVT of lower limbs in patients undergoing PFNA surgery.

Urchin-Like Cobalt-Copper (Hydr)oxides as an Efficient Water Oxidation Electrocatalyst.

The development of efficient and low-cost oxygen evolution reaction (OER) catalysts is essential for the generation of clean hydrogen energy from water splitting. Herein, a novel hierarchical urchin-like cobalt-copper (hydr)oxide in situ grown on copper foam (CoCuOx Hy (S)/CF) was synthesized through the electrochemical transformation of cobalt-copper sulfides (Co9 S8 -Cu1.81 S) via anodization process. This CoCuOx Hy (S)/CF anode exhibited a low overpotential (η) of 274 mV at a current density of 100 mA cm-2 with a robust durability over a period of 40 h when operated at 10 mA cm-2 . Further investigations imply that the unique nanowires aggregated urchin-like structure of CoCuOx Hy (S) derived from the in situ anion exchange process could facilitate the exposure of active sites and accelerate electron transfer. More importantly, the incorporation of copper resulted in an electronic delocalization around the cobalt species, which contributed to reach a high-valent catalytically active cobalt species and further improved the OER performance.

[Treatment of migrated lumbar disc herniation with percutaneous endoscopic lumbar discectomy and target foraminoplasty].

OBJECTIVE: To evaluate the clinical outcome of percutaneous endoscopic lumbar discectomy with target foraminoplasty in treating migrated lumbar disc herniation. METHODS: From June 2015 to January 2016, 25 patients with migrated lumbar disc herniation were treated with percutaneous endoscopic lumbar discectomy with target foraminoplasty. A total of 14 males and 11 females, aging from 23 to 52 years old (average: 37.6) were enrolled in this study. Discectomy occurred in L2,3 of 1 case, L3,4 of 3 cases, L4,5 of 12 cases, L5S1 of 9 cases. Preoperative, 1-week and 1-year postoperative visual analogue scale (VAS) scores were collected to evaluate lower back and leg pain; Oswestry Disability Index(ODI) was used to assess the lumbar function. RESULTS: All the patients were followed up for 12 to 19 months with an average of 15.2 months. The mean operation time was 108.6 min. No injury of dura, nerve root, or wound infection were found. Preoperative, 1-week and 1-year postoperative visual analogue scale(VAS) scores of lower back pain were 5.8±0.5, 2.5±0.4, 0.9±0.2, respectively, with significant differences among each other(P<0.05);VAS scores of leg pain were 7.1±0.6, 1.5±0.4, 0.7±0.6, respectively, with significant differences among each other(P<0.05). Lumbar ODI scores were 69.2±1.8, 22.5±4.7, 10.2±2.4 at the above time points and showed significant differences among each other(P<0.05). CONCLUSIONS: Percutaneous endoscopic lumbar discectomy with target foraminoplasty for migrated lumbar disc herniation showed advantages of less injuries, bleeding and complication. It also promotes rapid recovery, being curative safely and effectively.

[Application of the pedicle screw in the subaxial cervical spine].

OBJECTIVE: To research the clinical application of lower cervical pedicle screw fixation procedure. METHODS: From September 2011 to July 2013,32 patients underwent posterior pedicle screw-rod system fixation were retrospective analyzed includinig 20 males and 12 females with an average age of 56.4 years old ranging from 21 to 78 years. Among them, 10 patients were traumatic cervical spinal injury, 9 patients were cervical spinal canal tumors, 7 cases were posterior longitudinal ligament ossification of cervical vertebrae, 6 cases were multiple segmental cervical spondylopathy. Preoperatively, X-ray, computed tomography, magnetic resonance imaging and magnetic resonance angiography of the vertebral artery were performed in all patients. After the operation and during the follow-up,X-ray and computed tomography were performed to confirm the pedicle screw position. The accuracy of the pedicle screw placement was evaluated by 4 grades classification from Lee. The spinal cord function was assessed by ASIA impairment scale for traumatic patients and JOA score for non traumatic patients. RESULTS: Totally 144 pedicle screws performed on 32 patients from C3 to C7 involving 132 screws of grade 0,5 screws of grade 1,5 of screws grade 2 and 2 screws of grade 3 according to postoperative CT. There were 12 screws penetrating the pedicle cortex including 8 screws at lateral,2 screws at caudal, 1 screw at medial and 1 screw at cranial. The follow-up time was 12 to 33 months with an average of (21.0±1.5) months. The spinal cord function was not improved in 6 complete cervical spinal cord injury patients,but their paraplegic level descended 1 to 3 segments. Four incomplete cervical spinal cord injury patients' ASIA impairment scale was increased by 1 to 2 grades in average. The JOA score of 22 atraumatic patients increased from preoperative 11.5±0.8 to 15.9±0.6 of postoperative at 6 months (P<0.01). There were no screw loosening,screw pullout and screw-rod breakage. CONCLUSION: The lower cervical pedicle screw fixation can provide excellent 3D stability of the vertebral column. The operation risk and Complication could be minimized by adequate preoperative evaluation for appropriate cases and individual pedicle screw placement. It deserved the clinical expansion.