This study aimed to evaluate the impact of enhanced recovery after surgery (ERAS) protocols on the clinical outcomes of anterior cervical discectomy and fusion (ACDF). This retrospective study included eligible patients with 3-level cervical disc herniation treated with ACDF between April 2020 and April 2022, with a minimum 1-year follow-up. Patients were categorized into 2 groups based on whether they received an ERAS protocol (ERAS+ group) or standard perioperative care (ERAS- group). Key outcome measures included hospital length of stay, total cost, estimated blood loss, visual analogue scale pain scores, Neck Disability Index, Japanese Orthopaedic Association scores, perioperative opioid usage, complication rates, and Bridwell bone fusion grades. Statistical analyses were performed using Statistical Package for Social Sciences 24.0, with significance set at P < .05. The implementation of an ERAS protocol in patients undergoing multilevel ACDF may be associated with improved perioperative metrics, enhanced functional recovery, reduced opioid use, and lower complication rates in this retrospective analysis. Further prospective studies are warranted to confirm these observations. A total of 110 eligible patients were enrolled in our study. Compared with the ERAS- group, the ERAS+ group demonstrated significantly shorter hospital stays (3.6 ± 0.5 vs 4.3 ± 0.8 days, P < .05), lower total costs (18,569.2 ± 872.4 vs 21,201.9 ± 1160.8 CNY, P < .05), and reduced estimated blood loss (75.5 ± 14.6 vs 107.2 ± 27.5 mL, P < .05). The ERAS+ group also showed superior improvements in visual analogue scale, Neck Disability Index, and Japanese Orthopaedic Association scores at follow-up visits (P < .05). Furthermore, the ERAS+ group had significantly lower perioperative opioid consumption, a lower incidence of overall complications (P < .05), and better Bridwell fusion grades (P < .05).

The management of critical-sized bone defects has attracted heightened interest due to its challenging nature. To date, numerous engineered tissues incorporating nano-hydroxyapatite (nHap) have been proposed; however, nHap continues to encounter limitations, particularly regarding its inadequate immunomodulatory effects on bone. Therefore, needlelike nHap (NnHap)-based scaffolds were fabricated using a polylactic acid derivative and carboxymethyl chitosan. We hypothesize that NnHap@CP can not only promote bone immunomodulatory effects and angiogenesis in human umbilical vein endothelial cells through M2 subtype polarization but also directly promote osteogenesis in rat bone-marrow-derived mesenchymal stem cells (rBMSCs). Furthermore, mass spectrometry was employed to determine that osteoprotegerin/RANK/RANKL may represent a potential signaling pathway through which NnHap@CP enhances the osteogenesis of rBMSCs. In our study, NnHap@CP demonstrated a satisfactory effect on M2 subtype polarization in macrophages and enhanced osteogenesis in rBMSCs, as observed in an in vitro study. We employed NnHap@CP for the in vivo examination of a rat model with cranial critical-sized bone defects. We discovered that NnHap@CP significantly enhances new bone regeneration and neovascularization, potentially serving as an innovative treatment strategy for critical bone defects.

Substantial vascularization has emerged as a promising tissue engineering strategy for regenerating critical-sized bone defects. In this study, we developed an injectable smart hydrogel system (GH-LR) by incorporating roxadustat (RD)-loaded MgFe-layered double hydroxide nanoparticles into a gelatin methacryloyl/hyaluronic acid methacrylate (GH) hybrid matrix. This bioactive composite enables the sustained release of therapeutic agents (RD, Mg2+, and Fe3+), synergistically promoting angiogenesis-osteogenesis coupling. Comprehensive characterization confirmed the successful synthesis of GH-LR hydrogels with efficient drug encapsulation. In vitro studies demonstrated that GH-LR significantly enhanced endothelial tube formation in human umbilical vein endothelial cells and osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs), attributable to the prolonged release of bioactive molecules. Mechanistic investigations using RNA sequencing revealed activation of the PI3K-Akt pathways in BMSCs treated with GH-LR hydrogels, correlating with enhanced osteogenesis. In vivo, evaluation in a critical-sized calvarial defect model confirmed accelerated bone regeneration, as evidenced by upregulated expression of Runx2 and Col-1. The therapeutic effects stem from the synergistic interplay between locally sustained angiogenesis and osteogenesis induction. This biocompatible GH-LR system collectively represents an innovative approach for reconstructing large bone defects through controlled delivery and spatiotemporal coordination of pro-regenerative cues.

[This corrects the article DOI: 10.3389/fmed.2025.1729401.].

For the effective treatment of vertebral bone defects (BDs), the authors constructed an innovative hydroxyapatite (HAP) nanoparticle–hyaluronic acid (HA)–alginate (ALG) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2). The particle size of HAP was around 80 to 100 nm, and its addition markedly reduced the swelling rate and degradability of the HA-ALG scaffold while enhancing its compression resistance, enabling it to better support the BD site and provide a good proliferation environment for osteoblasts. Furthermore, HAP-HA-ALG effectively extended the half-life of rhBMP-2 by nearly 50-fold, allowing it to exert its osteogenic effects more consistently. In cellular experiments, the authors found that rhBMP-2@HAP-HA-ALG significantly enhanced the activity and migration ability of bone marrow mesenchymal stromal cells, as well as the expression level of related osteogenic proteins in cells, which better exerted osteoinductive and osteoconductive functions. In animal tests, rhBMP-2@HAP-HA-ALG could better facilitate the generation of new bone and bone trabecula at BD sites and markedly enhance the bone density level, thus shortening the repair time of BDs. Therefore, rhBMP-2@HAP-HA-ALG shows great potential in the restoration of vertebral BDs.

Anoxia remains a challenging problem to effective graft implantation in bone tissue engineering for managing large-size bone defects. One promising strategy is to provide immediate oxygen required for cell viability and graft maturation by introducing oxygen-generating biomaterials. In this study, we present a novel composite oxygen-generating scaffold by integrating oxygen-generating microspheres (OMs) comprised of emulsified calcium peroxides (CPOs) encapsulated in poly (lactic-co-glycolic acid; PLGA) into the gelatin methacryloyl (GelMA) hydrogel. The in vitro results reveal that the scaffold encapsulating 2% (w/v) OMs (OM@GelMA) mildly sustained oxygen production for approximately 16 days, and hence, established hypoxic niches with low oxygen tension (10–46 mmHg) under anoxic culture condition (0.2% oxygen) for the viability of bone marrow-derived mesenchymal stem cells (BMSCs) and their enhanced osteogenic differentiation, which may be induced by activation of HIF-1/β-catenin signaling pathway by the compatibly hypoxic level as one of the underlying molecular mechanisms verified via transcriptome sequencing, western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) tests on in vitro samples. Moreover, the oxygen-generating hydrogel could enhance angiogenesis of human umbilical vein endothelial cells (HUVECs) under anoxia by preserving cell viability, accelerating cell migration, promoting tube formation and activating angiogenic genes and proteins expression. In vivo studies using rat cranial critical-size defect models demonstrated that OM@GelMA significantly enhanced bone regeneration, effectively promoting bone defect repair. In summary, the OM@GelMA, as a novel endogenously oxygen-generating scaffold, holds great potential to facilitate bone tissue regeneration subject to oxygen-deprived scenarios. This study provides a new insight for future research and clinical applications in bone tissue engineering, particularly for large bone defect repair.

IntroductionThe natural polysaccharide-based injectable hydrogels have showed significant interest to use as 3D scaffolds for critical-sized bone defect repair.MethodsHere, we incorporated ZnO nanoparticles (NPs) into a newly synthesized water-soluble phosphocreatine-functionalized chitosan (CSMP) water solution to form an injectable hydrogel (CSMP-ZnO) via supramolecular combination between phosphate groups in CSMP and Zinc in ZnO NPs.ResultsThe phosphocreatine in this hydrogel not only provides sites to combine with ZnO NPs form supramolecular binding but also serves as the reservoir to control Zn2+ release. The results show that the lyophilized CSMP-ZnO hydrogels presented a porous structure with some small holes in the pore wall, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of ZnO NPs. In vitro experiments showed that the CSMP-ZnO hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CSMP hydrogel. The as-released Zn2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP2/SMAD signaling pathway. In vivo, the as-released Zn2+ ions promot osteoblastic proliferation and the mineralization of osteoblasts inside the CSMP-ZnO scaffolds. Immunofluorescence for RUNX2, COL-1, and CD31, showed that stable vasculature could be formed inside the CSMP-ZnO scaffolds.DiscussionBoth the in vitro and in vivo results demonstrate that CSMP-ZnO hydrogel shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.

Composite biomaterial systems facilitate regenerative medicine through component synergy. Herein, novel core-shell nanocomposites (N-HMMs) are prepared, with hollow mesoporous silica (HMSNs) as the core and magnesium-gallic acid metal-organic frameworks (Mg-MOFs) as the shell. N-HMMs are loaded with the small-molecule osteoinductive drug naringin (Nar) to form N-HMMs@Nar, which is integrated into methacrylate gelatin/polyethylene glycol diacrylate hydrogels (GelMA/PEGDA, GP) to construct N-HMMs@Nar@GP. N-HMMs@Nar@GP enables sustained release of Nar, bioactive Mg2+, and antioxidant gallic acid for synergistic anti-inflammation, osteogenesis, and angiogenesis of bone regeneration. GP adapts N-HMMs@Nar to the traumatic characteristics of bone defects and facilitates in situ treatments. In vitro studies have confirmed the composite materials' biocompatibility, osteoinductive differentiation, and angiogenesis capabilities. The ability of N-HMMs@Nar@GP to enhance osteogenesis and angiogenesis is demonstrated in an in vivo tibial defect model using micro-CT and histopathological analysis. Therefore, N-HMMs@Nar@GP holds significant potential for application in the repair of bone defects.

Objective sarcopenia and cervical degeneration disease are increasing with the age. The study aimed to investigate whether sarcopenia impact the clinical outcomes of patients underwent cervical laminoplasty. Method Data from 110 patients who underwent PCL between January 2018 and April 2023 at Ningbo No. 6 Hospital were retrospectively analyzed. Among them, 50 patients who met the inclusion and exclusion criteria were assigned to the sarcopenia-PCL (SPCL) group, and 60 patients were assigned to the non-SPCL (NPCL) group. Clinical and radiological data were collected from medical records. Baseline characteristics, operation-related parameters (hospital stay, cost), clinical outcomes (Neck Disability Index [NDI] and Japanese Orthopaedic Association Scores [JOA]), radiological outcomes (sagittal vertical axis [SVA] and range of motion [ROM]), Bridwell bone fusion grade, and complications were evaluated and compared. Result A total of 110 patients with a minimum 1-year follow-up were included in the analysis. There were no significant differences in age, gender, preoperative JOA, NDI, and ROM between the two groups (P > 0.05). The SPCL group showed significantly lower body mass index, bone mineral density, and skeletal muscle index compared with the NPCL group (P < 0.05). The SPCL group also had significantly longer hospital stays, greater blood loss, higher costs, and lower bone mineral density and skeletal muscle index compared with the NPCL group. At 6 months and 1 year follow-up, the NPCL group demonstrated significantly better clinical outcomes than the SPCL group (P < 0.05). In addition, the NPCL group showed significantly better SVA and ROM at 1 month and 1 year (P < 0.05). Moreover, there were significantly more cases with complications in the SPCL group (P < 0.05). Conclusion Sarcopenia may adversely affect the clinical outcomes of patients undergoing PCL. Further studies are warranted to confirm the influence of sarcopenia on this patient population.

BackgroundOsteoporosis vertebral compression fractures (OVCF) are common with the aging process. This study aimed to compare the effects of unilateral transverse process extrapedicular (UEPKP) and bilateral transpedicular percutaneous kyphoplasty (BTPKP) for patients with thoracolumbar OVCF.MethodsData from 136 patients with OVCF treated with single-level PKP in our hospital between May 2019 and April 2021 were studied. Patients were grouped based on surgical procedure: there were 62 patients in the UEPKP group and 74 in the BTPKP group. All clinical and radiological data were collected from medical records. Clinical outcomes, including visual analog scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores of the lumbar spine, were evaluated preoperatively, postoperatively, and at the follow-up visit. The radiological evaluations (anterior vertebral height rate and local kyphosis angle) and complications were also collected.ResultsAll patients had successfully improved after surgery. In the UEPKP group, patients showed a significantly shorter operating time and lower fluoroscopy frequency than patients in the BTPKP group (p < 0.05). However, a significantly better distribution score and cement volume were found in the BTPKP group (p < 0.05). The UEPKP group achieved a significantly better VAS score (0.6 ± 0.5 vs. 0.9 ± 0.8) and ODI (24.7 ± 3.1 vs. 27.5 ± 1.8) at the final follow-up visit than the BTPKP group (p < 0.05). The UEPKP group showed significantly worse radiological outcomes (anterior height rate and local kyphosis angle) at the 6- and 12-month follow-ups (p < 0.05). As for complications, the UEPKP group showed significantly fewer facet joint violations and intraspinal leakages (p < 0.05).ConclusionUEPKP could be a safe and effective alternative procedure for patients with thoracolumbar osteoporotic vertebral compression fracture, which possesses an apparent advantage in reducing intraspinal leakage and facet joint violation over BTPKP.

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.

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.

A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 degrees C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 +/- 6.33 MPa. Also, drugloaded scaffolds were treated against the most common microorganisms that cause the infection, such as S. aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome

Background Sarcopenia and osteoporosis vertebral compression fractures (OVCF) are common diseases that increase with age. This study aimed to investigate the effects of sarcopenia on OVCF patients after percutaneous kyphoplasty (PKP). Methods Data of 101 patients who were treated with single-level PKP between January 2021 and March 2022 at Ningbo No.6 Hospital were enrolled. Forty-five OVCF patients with sarcopenia who met our inclusion criteria were included in the Sarcopenia-PKP group (SPKP group), and 56 patients in the Normal-PKP group (NPKP group). All clinical and radiological data were collected from medical records. Baseline characteristics, operation-related parameters (operation time, time to ambulation, hospital stay, surgery segment), clinical outcomes (visual analog score [VAS], Oswestry Disability Index [ODI], Japanese Orthopaedic Association Scores [JOA] of lumber), radiological outcomes (vertebral anterior height rate and local kyphosis angle), Macnab score, and complications were evaluated and compared. Results There were no significant differences in age, sex, surgical segment preoperative VAS score, ODI, or JOA between the two groups (P > 0.05). The SPKP group had a significantly lower body mass index (BMI), bone mineral density (BMD), and smooth muscle index (SMI) than the NPKP group (P < 0.05). Significantly longer hospital stays and time to ambulation in SPKP group than NPKP group (3.7±0.8 vs 3.4±0.5 and 2.0±0.8 vs 1.6±0.5, P < 0.05). In SPKP group, significantly better clinical outcomes at 6- and 12-months follow-up were observed in NPKP group than SPKP group (P < 0.05), and NPKP group showed significantly better in vertebral anterior height rates than SPKP group after 6-month follow-up (P < 0.05). Moreover, there were significantly more cases of complications in the SPKP group (P < 0.05). Conclusion Sarcopenia could reduce the clinical effect of percutaneous kyphoplasty, and furthermore. Related studies are needed to verify the effect of sarcopenia on OVCF patients.

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.

外伤、肿瘤等情况导致的骨缺损常常造成严重的后果.尽管年轻人的骨骼具有较高的再生潜力,但血供中断仍会严重影响骨再生的能力,甚至导致骨坏死,尤其是股骨颈、舟状骨和距骨等血供相对较差的部位.近年来,间充质干细胞(MSC)已经广泛地应用于骨缺损的治疗中.然而,由于骨缺损导致的血液供应中断会导致相关组织的缺氧,从而使移植的MSC发生缺血缺氧性改变,最终导致骨再生失败.目前有不少关于产氧型生物材料的应用研究,在缺血性骨缺损的治疗方面取得了不同程度的效果.通过在缺血性骨缺损部位植入产氧型生物材料,可以进一步提高骨修复治疗的水平.本文回顾了骨折的病理生理过程,并讨论产氧型生物材料在进一步增强骨折修复中的应用,报道如下.

Numerous studies have previously demonstrated that long non-coding 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 IL-1 beta-induced chondrocyte injury remains unclear. It was hypothesized that FAM201A may exert a protective effect on IL-1 beta-induced 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 IL-1 beta-induced chondrocyte injury. A model of OA was established by stimulation C-28/I2 cell with IL-1 beta in vitro. The expression levels of FAM201A following IL-1 beta-induced chondrocyte injury were detected via reverse transcription-quantitative PCR. Luciferase reporter assay was used to assess the possible associations among FAM201A, miR-146a-5p and POU class 2 homeobox 1 (POU2F1). Chromatin immunoprecipitation assay was performed to analyze the interaction between POU2F1 and miR-146a-5p. ELISA, TUNEL and western blotting were performed to measure the level of inflammation, lactate dehydrogenase release, apoptosis and the expression of apoptosis-related proteins (Bcl-2, Bax, cleaved caspase 3 and cleaved caspase 9), respectively. The expression levels of FAM201A were found to be downregulated following IL-1 beta-induced chondrocyte injury. Overexpression of FAM201A exerted a protective effect against IL-1 beta-induced chondrocyte injury. In addition, FAM201A could upregulate the expression levels of POU2F1 by sponging miR-146a-5p. 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/miR-146a-5p/POU2F1 positive feedback loop in IL-1 beta-induced chondrocyte injury. The present study revealed the protective effects of the FAM201A/miR-146a-5p/POU2F1 positive feedback loop on IL-1 beta-induced chondrocyte injury and provided a potential therapeutic target for OA.

Objective To compare the clinical and radiological outcomes between microscopic anterior cervical discectomy and fusion (ACDF) and percutaneous endoscopic cervical keyhole foraminotomy (PECF) for single level unilateral cervical radiculopathy. Methods A total of 127 patients (59 in PECF VS 68 in ACDF) were enrolled in this study from April 2016 to May 2018 with a minimum follow-up of 2 years. Clinical data including baseline data, Neck Disability Index (NDI), and Visual Analogue Scale for neck and arm (VAS-n, VAS-a) were collected and compared. Radiological evaluation such as disc height, ROM of cervical, Cobb’s angle of cervical and Cobb’s angle of operated segment was measured by two experienced radiologists in twice. Results There was no significant difference between the two groups in the baseline data, and hospital stay was significantly decreased in PECF group than ACDF group (P < 0.001). PECF group did not yield superior better outcomes in NDI, VAS-a and VAS-n than ACDF group except at 1-month follow-up. As for radiological outcomes, PECF group has significantly better cervical motion, cervical angle and segmental angle than ADCF group at 12- and 24-month follow-up visit (P < 0.05); however, ACDF had shown better disc height restoration and maintenance than PECF (P < 0.05). More complications including surface hematoma and swallowing difficulty were occurred in ADCF group. Conclusion Percutaneous endoscopic cervical keyhole foraminotomy could be the alternative method for anterior cervical discectomy and fusion in selective cases. However, the indication should be fulfilled, more studies need to be conducted to further testify the efficacy of PECF.

Chronic stress is an important risk factor for mood disorders including depression. The decreased level of CREB (cAMP-responsive element binding)-regulated transcription coactivator 1 (CRTC1) expression in hippocampus may be involved in depression-like behavior in some stress-induced depression models. But the mechanism of CRTC1 in mediating depression-like behavior remains unknown. In this study, chronic unpredictable mild stress (CUMS)-treated mice showed depression-like behavior accompanied by the downregulation of CRTC1 in the hippocampus. Adeno-associated virus (AAV)-CRTC1-mediated overexpression of CRTC1 in the hippocampus by stereotactic brain injection could significantly prevent depression-like behavior in CUMS-treated mice. The above data reveal that the downregulation of hippocampal CRTC1 expression participates in CUMS-induced depression-like behavior. In order to explore the key targets regulated by CRTC1, AAV-mediated CRTC1 short hairpin (shRNA) was constructed to achieve knockdown of CRTC1 in the hippocampus, and then the hippocampi were collected for RNA-sequencing (RNA-seq). The RNA-seq data show that upregulated genes were enriched in stress and immune system-associated GO terms and pathways such as response to stress and external stimulus and regulation of immune response and that downregulated genes were enriched in neural activity such as synaptic transmission and cognitive behavior. We further provided RT-qPCR data that the inflammation-related factors including Gpr84, Tlr2, Lyz2, and Icam1 were significantly upregulated in the hippocampus of both CUMS- and CRTC1 shRNA-induced models, some of them were also validated in protein levels by Western blotting. We propose a hypothesis that CUMS induces downregulation of CRTC1, which might lead to depression-like behavior via neuroinflammation pathway. This study provides new explanation for the inflammatory hypothesis of depression and some clues for exploring the molecular mechanism of CRTC1 regulation.