Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Antimicrobial peptides (AMPs) are small molecule peptides that are widely found in living organisms with broad-spectrum antibacterial activity and immunomodulatory effect. Due to slower emergence of resistance, excellent clinical potential and wide range of application, AMP is a strong alternative to conventional antibiotics. AMP recognition is a significant direction in the field of AMP research. The high cost, low efficiency and long period shortcomings of the wet experiment methods prevent it from meeting the need for the large-scale AMP recognition. Therefore, computer-aided identification methods are important supplements to AMP recognition approaches, and one of the key issues is how to improve the accuracy. Protein sequences could be approximated as a language composed of amino acids. Consequently, rich features may be extracted using natural language processing (NLP) techniques. In this paper, we combine the pre-trained model BERT and the fine-tuned structure Text-CNN in the field of NLP to model protein languages, develop an open-source available antimicrobial peptide recognition tool and conduct a comparison with other five published tools. The experimental results show that the optimization of the two-phase training approach brings an overall improvement in accuracy, sensitivity, specificity, and Matthew correlation coefficient, offering a novel approach for further research on AMP recognition.
Anti-Bacterial Agents/chemistry* ; Amino Acid Sequence ; Antimicrobial Cationic Peptides/chemistry* ; Antimicrobial Peptides ; Natural Language Processing

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.

Purpose: Whether craniospinal irradiation (CSI) could be replaced by limited-field radiation in non-metastatic bifocal germinoma remains controversial. We addressed the issue based on the data from our series and the literature. Methods: Data from 49 patients diagnosed with non-metastatic bifocal germinoma at our hospital during the last 10 years were collected. The Pediatric Quality of Life Inventory 4.0 was used to evaluate health-related quality of life (HRQOL). Additionally, 81 patients identified from the literature were also analyzed independently. Results: In our cohort, 34 patients had tumors in the sellar/suprasellar (S/SS) plus pineal gland (PG) regions and 15 in the S/SS plus basal ganglia/thalamus (BG/T) regions. The median follow-up period was 52 months (range, 10 to 134 months). Our survival analysis showed that patients treated with CSI (n=12) or whole-brain radiotherapy (WBRT; n=34) had comparable disease-free survival (DFS; p=0.540), but better DFS than those treated with focal radiotherapy (FR; n=3, p=0.016). All 81 patients from the literature had tumors in the S/SS+PG regions. Relapses were documented in 4/45 patients treated with FR, 2/17 treated with whole-ventricle irradiation, 0/4 treated with WBRT, and 1/15 treated with CSI. Survival analysis did not reveal DFS differences between the types of radiation field (p=0.785). HRQOL analysis (n=44) in our cohort found that, compared with S/SS+PG germinoma, patients with BG/T involvement had significantly lower scores in social and school domains. However, HRQOL difference between patients treated with CSI and those not treated with CSI was not significant. Conclusion In patients with non-metastatic bifocal germinoma, it is rational that CSI could be replaced by limited-field radiation. HRQOL in patients with BG/T involvement was poorer.

Bone cement-augmented pedicle screw system demonstrates great efficacy in spinal disease treatments. However, the intrinsic drawbacks associated with clinically used polymethylmethacrylate (PMMA) cement demands for new bone cement formulations. On the basis of our previous studies, a novel injectable and biodegradable calcium phosphate-based nanocomposite (CPN) for the augmentation of pedicle screw fixation was systematically evaluated for its surgical feasibility and biomechanical performance by simulated and animal osteoporotic bone models, and the results were compared with those of clinical PMMA cement. ASTM-standard solid foam and open-cell foam models and decalcified sheep vertebra models were employed to evaluate the augmentation effects of CPN on bone tissue and on the cement-injected cannulated pedicle screws (CICPs) placed in osteoporotic bone. Surgical factors in CICPs application, such as injection force, tapping technique, screw diameter, and pedicle screw loosening scenarios, were studied in comparison with those in PMMA. When directly injected to the solid foam model, CPN revealed an identical augmentation effect to that of PMMA, as shown by the similar compressive strengths (0.73 ± 0.04 MPa for CPN group vs. 0.79 ± 0.02 MPa for PMMA group). The average injection force of CPN at approximately 40-50 N was higher than that of PMMA at approximately 20 N. Although both values are acceptable to surgeons, CPN revealed a more consistent injection force pattern than did PMMA. The dispersing and anti-pullout ability of CPN were not affected by the surgical factors of tapping technique and screw diameter. The axial pullout strength of CPN evaluated by the decalcified sheep vertebra model revealed a similar augmentation level as that of PMMA (1351.6 ± 324.2 N for CPN vs. 1459.7 ± 304.4 N for PMMA). The promising results of CPN clearly suggest its potential for replacing PMMA in CICPs augmentation application and the benefits of further study and development for clinical uses.

Three-dimensional (3D) printing technology is characterized by "inside-out" stack manufacturing. Compared with conventional technologies, 3D printing has the advantage of personalization and precision. Therefore, the shape and internal structure of the scaffolds made by 3D printing technology are highly biomimetic. Besides, 3D bioprinting can precisely deposit the biomaterials, seeding cells and cytokines at the same time, which is a breakthrough in printing technique and material science. With the development of 3D printing, it will make great contributions to the reconstruction of vertebrae and intervertebral disc in the future.
Biocompatible Materials ; Bioprinting ; Humans ; Intervertebral Disc ; growth & development ; Printing, Three-Dimensional ; Tissue Engineering ; methods ; Tissue Scaffolds

BACKGROUND:Scholars are stil looking for ideal bone tissue-engineered scaffolds, and three-dimensional (3D) printing technology is a novel construction method. In the meanwhile, bone extracel ular matrix is becoming a hotspot in osteogenic induction. OBJECTIVE:To construct the polycaprolactone/bone extracel ular matrix scaffold using 3D printing technology and co-culture method, and to detect its osteogenic property. METHODS:216 3D-printed polycaprolactone scaffolds were divided into group A (96 pores, n=72) and group B(48 pores, n=144). Passage 5 bone marrow mesenchymal stem cel s from Sprague-Dawley rats were seeded onto the two kinds of polycaprolactone scaffolds, and the group A was used for alizarin red staining and Masson staining, while the group B for col agen and glycosaminoglycan detection at 1, 2 and 3 weeks of incubation. Afterwards, the scaffolds at 1, 2 and 3 weeks of culture were decel ularized and labeled as groups AE1, AE2, AE3, BE1, BE2 and BE3. Then passage 5 bone marrow mesenchymal stem cel s from Sprague-Dawley rats were seeded onto each scaffold again, and the former three groups underwent alizarin red staining, and the latter three were used for calcium, alkaline phosphatase activity and DNA quantitative analysis at 1, 2 and 3 weeks of culture. RESULTS AND CONCLUSION:Masson staining, glycosaminoglycan and hydroxyproline quantitative analysis showed that the extracel ular matrix on the composite scaffold increased with time. Alkaline phosphatase activity revealed that the composite scaffold had a significantly stronger osteogenic differentiation than the normal polycaprolactone scaffold (P<0.05). Alizarin red staining and calcium quantitative analysis showed that the mineralization of the composite scaffold was more obvious than that of the normal polycaprolactone scaffold (P<0.05), but the total DNA analysis did not differ significantly between scaffolds. These results suggest that the composite scaffold with extracel ular matrix is constructed successful y using the 3D technology and co-culture method and exhibits a better osteoinductivity.

Objective To evaluate the bone repair capacity ofpolylactic acid-polyglycolic acid copolymer (PLGA)/collagen type Ⅰ (CoI) microspheres combined with BMSCs after being injected in intertrochanteric bone defect of osteoporotic female rats.Methods Prepared PLGA microspheres.The microspheres were coated with Col.BMSCs of the third passage were cultured with PLGA/CoI microspheres.Forty 3-month-old female SD rats were ovariectomized to establish osteoporotic animal models.The osteoporotic rats were randomly divided into 5 groups,including SHAM group,PBS group,Cell group,MS group and Cell+ MS group.There were 8 rats in each group.Different material was injected into the intertrochanteric bone defect site which was made with electric drill.Four rats of each group were sacrificed at 1 month and 3 months post-operation.The fenora were taken to measure the intertrochanteric bone mineral density (BMD) with DEXA and evaluate trabecular stucture with Micro CT.Results After 7 days of coculture,BMSCs seeded on PLGA/CoI microspheres had nice adherance and proliferation.There was no difference of BMC and BMD among all groups at 1 month post-operation.Tb.Th of Cell+MS group was higher than that of PBS group and MS group at 1 month post-operation.％Tb.Ar of Cell+MS group was higher than that of Cell group and MS group at 1 month post-operation.Tb.Sp of Cell+MS group had a tendence to decrease compared with other groups but there was no statistical difference at 1 month post-operation.After 3 months of operation,the BMC of Cell+MS group had a tendence to increase compared with that of PBS group and MS group but showed no statistical difference.BMD and Tb.Th of Cell+MS group was higher than those of other groups.％Tb.Ar of Cell+MS group was higher than that of SHAM group and PBS group.Tb.Sp of Cell+MS group had a tendence to reduce compared with other groups but showed no statistical difference.Conclusion The bone defect of osteoporotic site can be repaired 1 month after the injection of the PLGA/CoI microspheres combined with BMSCs.The trabecular reconstruction and bone quality of osteoporotic site can be improved 3 months after the injection.