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.

Comparison of staged lateral lumbar interbody fusion combined two-stage posterior screw fixation and two osteotomy strategies for adult degeneration scoliosis: a retrospective comparative study.

AIMS: The commonly used treatments of adult degeneration scoliosis (ADS) were posterior long segment screw fixation with osteotomies. Recently, lateral lumbar intervertebral fusion combined two-stage posterior screw fixation (LLIF + PSF) as a new strategy without osteotomy. Herein, this study aimed to compare the clinical and radiological outcomes among LLIF + PSF and pedicle subtraction osteotomy (PSO), posterior column osteotomies (PCO). METHODS: Totals of 139 ADS patients underwent operation with 2 years longer follow-up visit between January 2013 and January 2018 in Ningbo No.6 Hospital were enrolled into this study. 58 patients were included in PSO group, 45 in PCO group and 36 in LLIF + PSF group, The clinical and radiological data were reviewed from medical records. Baseline characteristic, perioperative radiological data (sagittal vertical axis (SVA), coronal balance (CB), Cobb angle of Mian curve (MC), Lumbar lordosis (LL), pelvic tilt (PT) and pelvic incidence-lumbar lordosis mismatch (PI-LL)), clinical outcomes (VAS of back and leg, Oswestry disability index (ODI) and Scoliosis Research Society 22-question Questionnaire (SRS-22)) and complications were evaluated and compared. RESULT: There were no significantly difference in baseline characteristics, preoperative radiological parameters and clinical outcomes among three groups. LLIF + PSF group was significantly shorter in operation time than other two groups (P < 0.05), whereas significant longer hospital stay was observed in LLIF + PSF group (P < 0.05). As for radiological parameters, LLIF + PSF group had significantly improvement in SVA, CB, MC, LL and PI-LL (P < 0.05). Moreover, LLIF + PSF group achieved significantly less correction loss in SVA, CB and PT than PSO and PCO group (1.5 ± 0.7 VS 2.0 ± 0.9 VS 2.2 ± 0.8, P < 0.05; 1.0 ± 0.4 VS 1.3 ± 0.5 VS 1.1 ± 0.7, P < 0.05 and 4.2 ± 2.8 VS 7.2 ± 3.1 VS 6.0 ± 2.8, P < 0.05). Significantly recovery in VAS of back and leg, ODI score and SRS-22 were found among all groups, however, LLIF + PSF shown significant better clinical therapy maintain at follow-up visit than other two groups (P < 0.05). There were no significantly difference in complications among groups (P = 0.66). CONCLUSION: Lateral lumbar interbody fusion combined two-stage posterior screw fixation (LLIF + PSF) can achieve comparable clinical therapy for adult degeneration scoliosis as osteotomy strategies. However, furthermore more studies need be taken for verifying the effect of LLIF + PSF in the future.

Bridging repair reinforced with artificial ligament as an internal brace for irreparable massive rotator cuff tears.

BACKGROUND: The irreparable massive rotator cuff tear (IMRCT) is challenging to manage. Although various surgical options have been proposed to treat IMRCTs, the optimal surgical technique remains controversial. Arthroscopic bridging patch repair is clinically used for treating IMRCTs, but the healing rate of the patch graft is negatively affected by superior shift of the humeral head. This study aimed to evaluate the clinical efficacy of artificial ligament as an internal brace (IB) reinforcing fascia lata autograft bridging repair (ABR) in the treatment of IMRCTs. METHODS: The data of 50 patients with IMRCTs who underwent ABR reinforced with artificial ligament as an IB (ABR + IB) (internal brace group) or ABR alone (control group) were retrospectively evaluated preoperatively and at 2-year follow-up. Clinical outcomes were assessed based on the shoulder activity, of which the strength was measured using a 0-10 points manual muscle test scale, American Shoulder and Elbow Surgeons score, and visual analog scale for pain. Imaging outcomes were evaluated based on acromiohumeral distance (AHD), Hamada grade, Goutallier grade, and the status of fascia lata grafts as per radiographs or magnetic resonance imaging findings. RESULTS: Both groups showed significantly better results in shoulder activity, American Shoulder and Elbow Surgeons score, visual analog scale score, and AHD at 2-year follow-up compared with preoperative levels (P < .001). Compared with the control group (n = 24), the internal brace group (n = 26) had better mean AHD (7.0 ± 1.4 mm vs. 5.9 ± 1.0 mm, P = .002), mean improvement in AHD (3.3 ± 1.5 mm vs. 2.0 ± 0.6 mm, P < .001), healing rate of autografts (92.3% vs. 54.2%, P = .002), and improvement rate of Hamada grade (73.1% vs. 41.7%, P = .025) at 2-year follow-up. No significant differences were found in active elevation, active external rotation, active internal rotation, abduction strength, external rotation strength, internal rotation strength, American Shoulder and Elbow Surgeons score, or visual analog scale between the 2 groups at 2-year follow-up. CONCLUSION: Both the ABR + IB and ABR improved the postoperative short-term clinical and imaging outcomes in managing IMRCTs, the ABR + IB is statistically superior to ABR alone in terms of healing rate of the bridging graft, AHD, and Hamada grade at 2-year follow-up, while further clinical investigations with larger sample size and longer follow-ups are required to validate the clinical significance of this novel technique for IMRCTs.

Preparation, characterization and biocompatibility of calcium peroxide-loaded polycaprolactone microparticles. / èšå·±å† é ¯åŒ è½½è¿‡æ°§åŒ–é’™å¾®ç²’çš„åˆ¶å¤‡ã€è¡¨å¾åŠå ¶ç”Ÿç‰©ç›¸å®¹æ€§ç ”ç©¶.

OBJECTIVES: To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. METHODS: The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O2 and H2O2 after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. RESULTS: Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O2 and H2O2 released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CONCLUSIONS: CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.

[CT and MRI fusion based on generative adversarial network and convolutional neural networks under image enhancement].

Aiming at the problems of missing important features, inconspicuous details and unclear textures in the fusion of multimodal medical images, this paper proposes a method of computed tomography (CT) image and magnetic resonance imaging (MRI) image fusion using generative adversarial network (GAN) and convolutional neural network (CNN) under image enhancement. The generator aimed at high-frequency feature images and used double discriminators to target the fusion images after inverse transform; Then high-frequency feature images were fused by trained GAN model, and low-frequency feature images were fused by CNN pre-training model based on transfer learning. Experimental results showed that, compared with the current advanced fusion algorithm, the proposed method had more abundant texture details and clearer contour edge information in subjective representation. In the evaluation of objective indicators, Q AB/F, information entropy (IE), spatial frequency (SF), structural similarity (SSIM), mutual information (MI) and visual information fidelity for fusion (VIFF) were 2.0%, 6.3%, 7.0%, 5.5%, 9.0% and 3.3% higher than the best test results, respectively. The fused image can be effectively applied to medical diagnosis to further improve the diagnostic efficiency.

Aldehyde dehydrogenase 2 alleviates monosodium iodoacetate-induced oxidative stress, inflammation and apoptosis in chondrocytes via inhibiting aquaporin 4 expression.

BACKGROUND: Knee osteoarthritis (KOA) is a common cause of disability among the elderly. We aimed to explore the effects of aldehyde dehydrogenase (ALDH) 2 on the progression of KOA and identifying the potential mechanisms. METHODS: First, ALDH2 expression in knee joint effusion of patients with KOA and the levels of oxidative stress-related markers were determined. After ALDH2 overexpression in monosodium iodoacetate (MIA)-treated SW1353 cells, cell viability was tested with CCK-8 assay. Subsequently, oxidative stress and inflammation-associated factors were measured. Meanwhile, cell apoptosis was assessed with TUNEL staining and expression of apoptosis-related proteins was detected by western blotting. To analyze the mechanism of ALDH2 in KOA, aquaporin 4 (AQP4) expression was determined using western blotting following ALDH2-upregulation. Subsequently, AQP4 was overexpressed to evaluate the changing of oxidative stress, inflammation and apoptosis in SW1353 cells exposed to MIA with ALDH2 overexpression. RESULTS: Results indicated that knee joint effusion with higher ALDH2 expression displayed lower oxidative stress. In addition, significantly upregulated ALDH2 expression was observed in MIA-treated SW1353 cells. ALDH2 overexpression oxidative stress, inflammation and apoptosis in SW1353 cells exposed to MIA. Moreover, MIA-triggered elevated expression of AQP4, which was reduced by ALDH2 overexpression. By contrast, AQP4-upregulation abrogated the inhibitory effects of ALDH2 on oxidative stress, inflammation and apoptosis in MIA-induced SW1353 cells. CONCLUSIONS: ALDH2 inactivates the expression of AQP4, by which mechanism the MIA-induced oxidative stress, inflammation and apoptosis injuries were alleviated, which provides a novel insight for understanding the mechanism of KOA and a promising target for the treatment of this disease.

Dynamic fixation is superior in terms of clinical outcomes to static fixation in managing distal tibiofibular syndesmosis injury.

PURPOSE: To analyze the current randomized controlled trials (RCTs) of dynamic fixations (DFs) and static fixations (SFs) in treating distal tibiofibular syndesmosis injuries (DTSIs). METHODS: The Cochrane Central Register of Controlled Trials, PubMed, and EMBASE were systematically searched according to the PRISMA guidelines to identify RCTs comparing the DFs and SFs for DTSIs. Included studies were assessed using the Cochrane Risk of Bias Tool. Postoperative functional scores, range of motion (ROM), complication rate, and incidence of reoperation were statistically analyzed using review manager software, and a p value of < 0.05 was considered statistically significant. RESULTS: Five RCTs with a total of 282 patients were included. Analysis revealed statistically significant differences in favor of DFs with regard to American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score at a follow-up less than 6 months (MD 5.29; 95% CI 0.99-9.59; p = 0.02; I2 = 0%) and at a follow-up more than 2 years (MD 7.53; 95% CI 3.30-11.76; p = 0.0005; I2 = 0%), Olerud-Molander ankle (OMA) score at 1 year follow-up (MD 4.62; 95% CI 0.91-8.32; p = 0.01; I2 = 14%), and overall postoperative complication rate (RR 0.22; 95% CI 0.07-0.77; p = 0.02; I2 = 73%). There was no significant difference between the DFs and SFs regarding ROM and incidence of reoperation. CONCLUSIONS: The DF procedure leads to significantly improved functional scores as well as lower rate of overall postoperative complications when compared with SF procedure. On the basis of results of this meta-analysis, the DF should be recommended for managing the DTSI. LEVEL OF EVIDENCE: I.

A randomized controlled trial: comparing extracorporeal shock wave therapy versus local corticosteroid injection for the treatment of carpal tunnel syndrome.

PURPOSE: Extracorporeal shock wave therapy (ESWT) has been reported as a new therapy for carpal tunnel syndrome (CTS). However, few studies have compared ESWT with the local corticosteroid injection (LCI). METHODS: In this study, a randomized controlled trial comparing 30 patients with ESWT and 25 patients treated with LCI was conducted. The clinical outcomes were obtained with tests including the visual analog scale (VAS) for pain and paresthesia, the Boston Carpal Tunnel Questionnaire (BQ), and a nerve conduction study, before the study started and at three, nine, and 12 weeks after the start of the treatment. RESULTS: Significantly greater improvement in the VAS and BQ scores was noted for the ESWT group than for the LCI group (P < 0.05). For the nerve conduction study, there was a significant improvement in the median nerve sensory nerve action potential distal latency at the nine and 12-week follow-ups for the ESWT group. CONCLUSIONS: ESWT is a useful noninvasive short-term treatment for mild to moderate carpal tunnel syndrome and elicits a better recovery than LCI does, but more research is needed to test the clinical outcomes of ESWT.

The Anatomical Variation of the Scapular Spine in A Chinese Population.

BACKGROUND The occurrence of fractures and risks following reverse total shoulder arthroplasty (rTSA) is common due to the variation of scapular spine (SS). Therefore, the consideration of the variable osteological features of SS prior to surgery may prove to be significant for the implementation of rTSA. This study aimed to propose a classification of SS through particular and quantitative parameters. MATERIAL AND METHODS In total, 354 intact dry scapulae were geometrical measured and classified on account of anatomical characteristics and the shapes of SS. RESULTS Type I SS was found, and this was the most frequency was type (27.97%). The least common type was type II. The type of SS had a direct association with bone stock and bone mineral density. Type II represented an association with a much thinner spine and restricted cortical and cancellous bone; types II and V were also associated with a crooked SS, which had a more complex morphology. CONCLUSIONS This study offered a comprehensive classification of SS in the Chinese population. On the whole, this study indicates that knowledge of the morphological variations of SS can prompt the diagnosis of scapular fractures and can promote more successful rTSA procedures, and the relative clinical trial is necessary to support it.

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.

Artificial intelligence detection of distal radius fractures: a comparison between the convolutional neural network and professional assessments.

Background and purpose - Artificial intelligence has rapidly become a powerful method in image analysis with the use of convolutional neural networks (CNNs). We assessed the ability of a CNN, with a fast object detection algorithm previously identifying the regions of interest, to detect distal radius fractures (DRFs) on anterior-posterior (AP) wrist radiographs. Patients and methods - 2,340 AP wrist radiographs from 2,340 patients were enrolled in this study. We trained the CNN to analyze wrist radiographs in the dataset. Feasibility of the object detection algorithm was evaluated by intersection of the union (IOU). The diagnostic performance of the network was measured by area under the receiver operating characteristics curve (AUC), accuracy, sensitivity, specificity, and Youden Index; the results were compared with those of medical professional groups. Results - The object detection model achieved a high average IOU, and none of the IOUs had a value less than 0.5. The AUC of the CNN for this test was 0.96. The network had better performance in distinguishing images with DRFs from normal images compared with a group of radiologists in terms of the accuracy, sensitivity, specificity, and Youden Index. The network presented a similar diagnostic performance to that of the orthopedists in terms of these variables. Interpretation - The network exhibited a diagnostic ability similar to that of the orthopedists and a performance superior to that of the radiologists in distinguishing AP wrist radiographs with DRFs from normal images under limited conditions. Further studies are required to determine the feasibility of applying our method as an auxiliary in clinical practice under extended conditions.

Metastatic Pulmonary Adenocarcinoma of the Talus: A Case Report.

Tumors rarely metastasize to the foot bones; however, a misdiagnosis can lead to a poor outcome. These metastatic tumors can cause foot pain and other symptoms in patients who are asymptomatic for the primary tumor. To accurately diagnose acrometastases, the attending physician must have a high index of suspicion and conduct a thorough examination and appropriate diagnostic testing. We present a rare case of metastatic pulmonary adenocarcinoma of the talus, which was initially misdiagnosed as a benign bone cyst. After pulmonary adenocarcinoma was diagnosed, the patient received multidrug treatment for the primary and metastatic lesions and was still responding well at the 12-month follow-up visit.

The clinical effect of unilateral decompressive laminectomy plus fusion with unilateral biportal endoscopic technique for single level lumbar spinal stenosis.

PURPOSE: This study aimed to compare and analyze the effectiveness of unilateral biportal endoscopic (UBE) decompressive laminectomy plus fusion and microscope-assisted open decompressive laminectomy plus fusion. METHODS: A total of 143 patients with lumbar spinal stenosis were enrolled in this study between March 2020 and February 2021 with a minimum 2 years follow-up visit to our hospital. Sixty-five patients underwent the unilateral biportal endoscopic technique and were assigned to the UBE group, and the remaining 78 patients with microscope assistant were assigned to the Microscope group. The baseline characteristics, clinical outcomes, and radiological data were retrospectively collected and analyzed, as well as Clinical outcomes, radiological data and complications. RESULTS: There were no significant differences between the two groups in terms of baseline characteristics (P > 0.05). The UBE group was demonstrated to be significantly superior in CRP, drainage, blood loss, treatment cost and Hospital stay than the Microscope group (P < 0.05), whereas a significant longer operation time was observed (P < 0.05). The VAS-B, ODI, and JOA-L scores of the UBE group at 1 year follow-up were significantly greater than those of the Microscope group (P < 0.05). Regarding radiological data, there were no significant differences in the section area of the spinal canal and fusion grade between the two groups (P > 0.05). CONCLUSION: In view of the satisfactory clinical outcomes of patients and notable decompression at the stenosed segment, UBE is a feasible, minimally invasive technique for single level lumbar canal stenosis.

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.

Induction of cervical disc degeneration and discogenic pain by low concentration Propionibacterium acnes infection: an in vivo animal study.

BACKGROUND: Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain. METHODS: Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3-C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP. RESULTS: IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated. CONCLUSION: P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.

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.

Corrigendum: Can oblique lateral interbody fusion (OLIF) create more lumbosacral lordosis in lumbar spine surgery than minimally invasive transforaminal interbody fusion (MIS-TLIF)?

[This corrects the article DOI: 10.3389/fsurg.2022.1063354.].

Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells.

Oxygenating biomaterials can alleviate anoxic stress, stimulate vascularization, and improve engraftment of cellularized implants. However, the effects of oxygen-generating materials on tissue formation have remained largely unknown. Here, we investigate the impact of calcium peroxide (CPO)-based oxygen-generating microparticles (OMPs) on the osteogenic fate of human mesenchymal stem cells (hMSCs) under a severely oxygen deficient microenvironment. To this end, CPO is microencapsulated in polycaprolactone to generate OMPs with prolonged oxygen release. Gelatin methacryloyl (GelMA) hydrogels containing osteogenesis-inducing silicate nanoparticles (SNP hydrogels), OMPs (OMP hydrogels), or both SNP and OMP (SNP/OMP hydrogels) are engineered to comparatively study their effect on the osteogenic fate of hMSCs. OMP hydrogels associate with improved osteogenic differentiation under both normoxic and anoxic conditions. Bulk mRNAseq analyses suggest that OMP hydrogels under anoxia regulate osteogenic differentiation pathways more strongly than SNP/OMP or SNP hydrogels under either anoxia or normoxia. Subcutaneous implantations reveal a stronger host cell invasion in SNP hydrogels, resulting in increased vasculogenesis. Furthermore, time-dependent expression of different osteogenic factors reveals progressive differentiation of hMSCs in OMP, SNP, and SNP/OMP hydrogels. Our work demonstrates that endowing hydrogels with OMPs can induce, improve, and steer the formation of functional engineered living tissues, which holds potential for numerous biomedical applications, including tissue regeneration and organ replacement therapy.

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis.

ABSTRACT: Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein-protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.