Percutaneous Intradiscal Radiofrequency Thermocoagulation Combined with Sinuvertebral Nerve Ablation for the Treatment of Discogenic Low Back Pain.

BACKGROUND: Percutaneous intervertebral radiofrequency thermocoagulation (PIRFT) and sinuvertebral nerve ablation (SVNA) are commonly used clinical treatments for discogenic low back pain (DLBP). However, they have been reported to have low efficacy rates of approximately 16.5%-26.5%, especially in the medium to long term. OBJECTIVES: To investigate whether PIRFT combined with SVNA can reduce pain and improve clinical outcomes in patients with DLBP. STUDY DESIGN: This is a prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: Following the inclusion and exclusion criteria, 195 patients were enrolled in this study and randomly divided into 3 groups of 65 patients each and treated with PIRFT+SVNA, PIRFT, or SVNA. Postoperative follow-ups were done at one week, one month, 3 months, 6 months, and 12 months. The demographic characteristics, relevant surgical information, and observed complications of all groups were recorded. The efficacy of the surgeries was evaluated using the visual analog scale (VAS), Oswestry disability index (ODI), and modified Macnab criteria. RESULTS: In total, 167 patients, comprising 81 men and 86 women (aged 28-75 years), were included in this study and completed postoperative follow-ups. There were 54 patients in the combined PIRFT and SVNA (PIRFT+SVNA) group, 58 patients in the PIRFT group, and 55 patients in the SVNA group. All groups were comparable because there were no significant differences in gender, age, disease duration, follow-up time, surgical segments and presence of high-intensity zones of the groups (P > 0.05). In addition, the efficacy of the PIRFT+SVNA group was significantly higher than that of the PIRFT and SVNA groups as assessed by the modified Macnab criteria (P = 0.032). Surgery was successfully completed in all 3 groups, and VAS and ODI improved at all postoperative time points in all 3 groups compared to the preoperative scores. The differences between the VAS and ODI scores preoperation and 12 months postoperation were not statistically significant between all 3 groups. However, at one week, one month, 3 months, and 6 months after surgery, the VAS and ODI scores were lower in the PIRFT+SVNA group compared to the PIRFT and SVNA groups. The difference in VAS scores among the 3 groups was most significant at one week postoperation, and the difference in ODI scores was most significant at one month postoperation. The VAS and ODI improvement rates of the 3 groups showed significant improvement at one week, one month, 3 months, and 6 months postoperation (P < 0.05). There was no significant difference among the 3 groups at 12 months postoperation (P > 0.05). LIMITATIONS: This study was limited by its small sample size in a single-center study. CONCLUSIONS: In DLBP, the sinuvertebral nerve (SVN) is the main nerve involved in the lumbar disc pain signaling pathway, and compared with PIRFT and SVNA alone, combined PIRFT and SVNA treatment may provide more satisfactory pain relief and functional improvement at an early stage.

Three dimensional-printed artificial disc replacement for single-level cervical spondylosis: a cohort study.

PURPOSE: To compare the clinical efficacy of 3D-printed artificial discs with that of ACDF for treating cervical spondylosis. METHODS: This was a retrospective analysis of 73 patients with single-level cervical spondylosis who met the inclusion criteria between January 2020 and December 2022 at XX Hospital. The patients were divided: 38 patients in the ACDF group and 35 patients in the CADR group. Patient general information, including operation time and intraoperative blood loss, was collected. The clinical effect of the combination therapy was evaluated by the VAS, JOA, and NDI. The radiological effect was evaluated using the ROM test. Ethics No. 201,606,009. RESULTS: The average follow-up times in the ACDF and CADR groups were 28.24 ± 4.65 and 29.11 ± 5.06 months, respectively (P = 0.443). Clinical symptoms (evaluated by VAS, NDI, and JOA) are significantly improved in both the ACDF and CADR groups with similar efficacy. The preoperative ROM of the ACDF group was 40.03 ± 8.79, while that of the CADR group was 42.11 ± 7.98 (P = 0.293). However, the postoperative ROM in the ACDF group was 35.29 ± 7.23, which was lower than that in the CADR group (40.43 ± 6.98) (P = 0.003). Furthermore, only one patient in the ACDF group experienced mild dysphagia after surgery, and the patient recovered within three days. ASD occurred in nine patients in the ACDF group and in two patients in the CADR group (Χ²=4.597, P = 0.032). CONCLUSIONS: Compared with ACDF, 3D-printed artificial discs for treating single-level cervical spondylosis have proven to be clinically effective; it associated with less blood loss and a lower incidence of ASD, and maintain a better cervical ROM.

Comparison of two surgical approaches in treating children with thoracolumbar junction tuberculosis: a multicenter study.

OBJECTIVES: We conducted a multicenter retrospective analysis to compare the clinical outcomes and complications associated with the posterior-anterior and posterior-only approaches in treating Thoracolumbar Junction (TLJ) Tuberculosis (TB) in children aged 3-10 years. METHODS: Herein, 52 TLJ TB patients (age range = 3-10 years; mean age = 6.8 ± 2.2 years; females = 22; males = 30) treated with debridement, fusion, and instrumentation were recruited from two hospitals in China between May 2008 and February 2022, and their clinical data were reviewed retrospectively. Among them, 24 group A patients and 28 group B patients underwent the posterior-anterior and posterior-only approaches, respectively. The two groups were assessed for surgical time, blood loss, hospitalization duration, operative complications, inflammatory indicators, Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, kyphosis angles, and neurologic functions. Results or differences with P < 0.05 were considered statistically significant. RESULTS: The average follow-up period was 37.5 ± 23.3 months. Compared to group A patients, group B patients exhibited significantly lower surgical time, blood loss amount, time it took to stand, and hospitalization duration, as well as fewer complications. Notably, the Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) values of patients in both groups returned to normal one year post-surgery. Furthermore, compared to the preoperative values, patients' VAS and ODI scores, as well as neurological functions and kyphosis angles, were significantly improved postoperatively and at the final follow-up, but with no statistically significant differences between the two groups. Moreover, there was no internal fixation failure or TB recurrence, and all patients exhibited solid bone fusion at the last follow-up. CONCLUSION: For pediatric TLJ TB involving no or at most two segments, both posterior-anterior and posterior-only approaches could effectively remove lesions and decompress the spinal cord, restore spinal stability, correct kyphosis, and prevent deformity deterioration. Nonetheless, the posterior-only approach can more effectively shorten the surgical time, reduce related trauma and complications, and promote rapid recovery, making it a safer and highly preferable minimally invasive approach.

A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs.

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.

Laponite modified methacryloyl gelatin hydrogel with controlled release of vascular endothelial growth factor a for bone regeneration.

Reconstruction of bone defects has long been a major clinical challenge. Limited by the various shortcomings of conventional treatment like autologous bone grafting and inorganic substitutes, the development of novel bone repairing strategies is on top priority. Injectable biomimetic hydrogels that deliver stem cells and growth factors in a minimally invasive manner can effectively promote bone regeneration and thus represent a promising alternative. Therefore, in this study, we designed and constructed an injectable nanocomposite hydrogel co-loaded with Laponite (Lap) and vascular endothelial growth factor (VEGF) through a simplified and convenient scheme of physical co-mixing (G@Lap/VEGF). The introduced Lap not only optimized the injectability of GelMA by the electrostatic force between the nanoparticles, but also significantly delayed the release of VEGF-A. In addition, Lap promoted high expression of osteogenic biomarkers in mesenchymal stem cells (MSCs) and enhanced the matrix mineralization. Besides, VEGF-A exerted chemotactic effects recruiting endothelial progenitor cells (EPCs) and inducing neovascularization. Histological and micro-CT results demonstrated that the critical-sized calvarial bone defect lesions in the SD rats after treated with G@Lap/VEGF exhibited significant in vivo bone repairing. In conclusion, the injectable G@Lap/VEGF nanocomposite hydrogel constructed in our study is highly promising for clinical transformation and applications, providing a convenient and simplified scheme for clinical bone repairing, and contributing to the further development of the injectable biomimetic hydrogels.

[Brief history and application prospect of robotic spine surgery].

Spinal robotics has rounded out twenty years in clinical, is mainly used for pedicle screw placement at present, can significantly increase the accuracy of screw placement and reduce radiation exposure to the patient and the surgeon. In the future, haptic feedback, automatic collision avoidance, and other technologies will further expand its application to complete precise operations such as decompression and correction, providing safety guarantee for the implementation of complex spinal surgery.

[Effectiveness comparison of robot-assisted and traditional freehand technology in treatment of atlantoaxial dislocation].

Objective: To compare the effectiveness of robot-assisted and traditional freehand screw placement in the treatment of atlantoaxial dislocation. Methods: The clinical data of 55 patients with atlantoaxial dislocation who met the selection criteria between January 2021 and January 2024 were retrospectively analyzed. According to different screw placement methods, they were divided into the traditional group (using the traditional freedhand screw placement, 31 cases) and the robot group (using the Mazor X robot-assisted screw placement, 24 cases). There was no significant difference in gender, age, body mass index, etiology, and preoperative visual analogue scale (VAS) score, cervical spine Japanese Orthopaedic Association (JOA) score between the two groups ( P>0.05). The operation time, intraoperative blood loss, operation cost, and intraoperative complications were recorded and compared between the two groups. The VAS score and cervical spine JOA score were used to evaluate the improvement of pain and cervical spinal cord function before operation and at 1 month after operation. CT examination was performed at 3 days after operation, and the accuracy of screw placement was evaluated according to Neo grading criteria. Results: All the 55 patients successfully completed the operation. The operation time, intraoperative blood loss, and operation cost in the robot group were significantly higher than those in the traditional group ( P<0.05). A total of 220 C 1 and C 2 pedicle screws were inserted in the two groups, and 94 were inserted in the robot group, with an accuracy rate of 95.7%, among them, 2 were inserted by traditional freehand screw placement due to bleeding caused by intraoperative slip. And 126 pedicle screws were inserted in the traditional group, with an accuracy rate of 87.3%, which was significantly lower than that in the robot group ( P<0.05). There were 1 case of venous plexus injury in the robot group and 3 cases in the traditional group, which improved after pressure hemostasis treatment. No other intraoperative complication such as vertebral artery injury or spinal cord injury occurred in both groups. All patients were followed up 4-16 months with an average of 6.6 months, and there was no significant difference in the follow-up time between the two groups ( P>0.05). Postoperative neck pain significantly relieved in both groups, and neurological symptoms relieved to varying degrees. The VAS score and cervicle spine JOA score of both groups significantly improved at 1 month after operation when compared with preoperative scores ( P<0.05), and there was no significant difference in the score change between the two groups ( P>0.05). Conclusion: In the treatment of atlantoaxial dislocation, the accuracy of robot-assisted screw placement is superior to the traditional freedhand screw placement.

[Comparative study of computer-assisted and robot-assisted atlantoaxial pedicle screw implantation for reversible atlantoaxial dislocation].

Objective: To investigate the effectiveness of computer-assisted and robot-assisted atlantoaxial pedicle screw implantation for the treatment of reversible atlantoaxial dislocation (AAD). Methods: The clinical data of 42 patients with reversible AAD admitted between January 2020 and June 2023 and met the selection criteria were retrospectively analyzed, of whom 23 patients were treated with computer-assisted surgery (computer group) and 19 patients were treated with Mazor X spinal robot-assisted surgery (robot group). There was no significant difference in gender, age, T value of bone mineral density, body mass index, etiology, and preoperative Japanese Orthopaedic Association (JOA) score, Neck Dysfunction Index (NDI) between the two groups ( P>0.05). The operation time, screw implantation time, intraoperative blood loss, hand and wrist radiation exposure, and complications were recorded and compared between the two groups. Gertzbein classification was used to evaluate the accuracy of screw implantation. JOA score and NDI were used to evaluate the function before operation, at 3 days after operation, and at last follow-up. At last follow-up, the status of screws and bone fusion were observed by neck three-dimensional CT. Results: The operation time and hand and wrist radiation exposure of the computer group were significantly longer than those of the robot group ( P<0.05), and there was no significant difference in the screw implantation time and intraoperative blood loss between the two groups ( P>0.05). All patients were followed up 11-24 months, with an average of 19.6 months. There was no significant difference in the follow-up time between the two groups ( P>0.05). There was no significant difference in the accuracy of screw implantation between the two groups ( P>0.05). Except for 1 case of incision infection in the computer group, which improved after antibiotic treatment, there was no complication such as nerve and vertebral artery injury, screw loosening, or breakage in the two groups. The JOA score and NDI significantly improved in both groups at 3 days after operation and at last follow-up ( P<0.05) compared to those before operation, but there was no significant difference between the two groups ( P>0.05). At last follow-up, 21 patients (91.3%) in the computer group and 18 patients (94.7%) in the robot group achieved satisfactory atlantoaxial fusion, and there was no significant difference in the fusion rate between the two groups ( P>0.05). Conclusion: Computer-assisted or robot-assisted atlantoaxial pedicle screw implantation is safe and effective, and robotic navigation shortens operation time and reduces radiation exposure.

[Curative effect analysis of anterior cervical discectomy and fusion in patients with cervical spondylosis of vertebral artery type].

OBJECTIVE: To investigate the clinical effect of anterior cervical discectomy and fusion (ACDF) in the treatment of cervical spondylosis of vertebral artery type(CSA). METHODS: The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed. There were 25 males and 17 females, aged from 30 to 74 years old with an average of (53.9±11.0) years old. There were 18 cases with single-segment lesions, 17 cases with two-segment lesions, and 7 cases with three-segment lesions. The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score (CHE), the Neck Disability Index (NDI) and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months. RESULTS: All 42 ACDF patients were followed up for 6 to 30 months with an average of (14.0±5.2) months. The operative time ranged from 95 to 220 min with an average of (160.38±36.77) min, the intraoperative blood loss ranged from 30 to 85 ml with an average of (53.60±18.98) ml. Tow patients had mild postoperative dysphagia, which improved with symptomatic treatment such as nebulized inhalation. CHE score decreased from (4.05±0.96) preoperatively to (2.40±0.70) at 6 months postoperatively (t=12.97, P<0.05). The number of improved vertigo at 6 months postoperatively was 38, with an improvement rate of 90.5%. NDI score was reduced from (34.43±8.04) preoperatively to (20.76±3.91) at 6 months postoperatively (t=11.83, P<0.05). The cervical curvature Cobb angle improved from (8.04±6.70)° preoperatively to (12.42±5.23)° at 6 months postoperatively (t=-15.96, P<0.05). CONCLUSION: The ACDF procedure has outstanding clinical efficacy in treating CSA. The operation can rapidly relieve patients' episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature. However, it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in patients, and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.

Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through MALAT1/miR-138-5p/SLC7A11 Coexpression Regulation.

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.

Weight-adjusted waist index is a potential early predictor of degraded bone microarchitecture: A cross-sectional study of the national health and nutrition examination survey 2007-2008.

PURPOSE: This study aimed to investigate the association between weight-adjusted waist index (WWI) and trabecular bone score (TBS) and to assess the ability of WWI to identify individuals with degraded bone microarchitecture (DBMA). METHODS: This cross-sectional study included participants aged 20 and older from the National Health and Nutrition Examination Survey. Furthermore, WWI was calculated by waist circumference and body weight. In addition, linear regression models were employed to investigate the association between WWI and TBS, while logistic regression models were employed to determine the association between WWI and the risk of DBMA. Finally, the performance of WWI in identifying individuals with DBMA was using the receiver operating characteristic (ROC) curves with area under the ROC curve. RESULTS: A total of 4,179 participants with a mean age of 49.90 years were included in the final analysis. WWI was negatively associated with TBS and positively associated with an increased risk of DBMA. Furthermore, the associations between WWI and TBS, as well as DBMA risk, were stable regardless of stratification by age, sex, race, or body mass index (BMI). Moreover, WWI achieved good performances in identifying individuals with DBMA or low TBS. In addition, the combination of WWI and BMI showed better performances in identifying individuals with DBMA or low TBS than WWI or BMI alone. CONCLUSION: WWI established a negative association with TBS and a positive association with the risk of DBMA. Clinicians should be alert to the potential risk of DBMA among individuals with high WWI. Moreover, WWI, alone or in combination with BMI, has the potential to serve as an early screening strategy in identifying individuals with DBMA.

Magnesium malate-modified calcium phosphate bone cement promotes the repair of vertebral bone defects in minipigs via regulating CGRP.

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

Human Placenta Decellularized Extracellular Matrix Hydrogel Promotes the Generation of Human Spinal Cord Organoids with Dorsoventral Organization from Human Induced Pluripotent Stem Cells.

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.

Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping.

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)-ß/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-ß/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

Electric field induced the changes in structure and function of human transforming growth factor beta receptor type I: from molecular dynamics to docking.

The transforming growth factor beta (TGF-ß) signaling pathway is believed to play essential roles in several physiological activities, including cancer. TGF-ß receptor type I (TBR-I) is a key membrane receptor protein in the TGF-ß signaling pathway, which relates to many intracellular biological effects. In recent years, cold atmospheric plasma (CAP) has been found to have promising prospects in selective anticancer therapy and has confirmed its essential role in the TGF-ß signaling pathway. However, the ambiguous effect of CAP-induced electric field (EF) on TBR-I still limits the application of CAP in clinical therapy. Molecular dynamics is applied to assess the effect of EF on the structure of the extracellular domain of TBR-I using a series of indicators and methods, and then we discuss the ligand binding ability of TBR-I. Results show that moderate EF intensities' structural restraints may contribute to the structural stability and ligand-binding ability of TBR-I, but an EF higher than 0.1 V/nm will be harmful. What's more, EF induces a change in the docking interface of TBR-I, showing the conformation and position of special sequences of residues decide the ligand binding surface. The relevant results suggest that CAP-induced EF plays a crucial role in receptor-receptor interaction and provides significant guidelines for EF-related anticancer therapy.Communicated by Ramaswamy H. Sarma.

Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis.

Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein-protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP.

Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury.

Microglia/macrophages are major contributors to neuroinflammation in the central nervous system (CNS) injury and exhibit either pro- or anti-inflammatory phenotypes in response to specific microenvironmental signals. Our latest in vivo and in vitro studies demonstrated that curcumin-treated olfactory ensheathing cells (aOECs) can effectively enhance neural survival and axonal outgrowth, and transplantation of aOECs improves the neurological outcome after spinal cord injury (SCI). The therapeutic effect is largely attributed to aOEC anti-inflammatory activity through the modulation of microglial polarization from the M1 to M2 phenotype. However, very little is known about what viable molecules from aOECs are actively responsible for the switch of M1 to M2 microglial phenotypes and the underlying mechanisms of microglial polarization. Herein, we show that Interleukin-4 (IL-4) plays a leading role in triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 markers IL­1ß, IL­6, tumour necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) and elevating the levels of M2 markers Arg-1, TGF-ß, IL-10, and CD206. Strikingly, blockade of IL-4 signaling by siRNA and a neutralizing antibody in aOEC medium reverses the transition of M1 to M2, and the activated microglia stimulated with the aOEC medium lacking IL-4 significantly decreases neuronal survival and neurite outgrowth. In addition, transplantation of aOECs improved the neurological function deficits after SCI in rats. More importantly, the crosstalk between JAK1/STAT1/3/6-targeted downstream signals and NF-κB/SOCS1/3 signaling predominantly orchestrates IL-4-modulated microglial polarization event. These results provide new insights into the molecular mechanisms of aOECs driving the M1-to-M2 shift of microglia and shed light on new therapies for SCI through the modulation of microglial polarization.

Comparison of the S8 navigation system and the TINAVI orthopaedic robot in the treatment of upper cervical instability.

The objective is to compare the clinical efficacy and safety of the S8 navigation system and the Tinavi orthopaedic surgery robot in the treatment of upper cervical instability. The research methods adopted are as follows. The clinical data of patients with upper cervical instability who underwent surgery from May 2021 to December 2021 were analysed retrospectively. Patients were divided into a navigation group (assisted by the S8 navigation system) and a tinavi group (assisted by the Tinavi robot) according to the auxiliary system used. Computed tomography and digital radiography were performed after the operation. The accuracy of pedicle screw placement was evaluated using the criteria put forward by Rampersaud. Degree of facet joint violation, visual analogue scale score, neck disability index and Japanese orthopaedic association score were recorded and assessed during follow-up examinations in both groups. Record two groups of surgery-related indicators. Record the complications of the two groups. A total of 50 patients were included. 21 patients in the navigation group and 29 in the tinavi group. The results of the study are as follows. The average follow-up time was 12.1 months. There was no significant difference in nail placement accuracy between the navigation and tinavi groups (P > 0.05); however, the navigation group had a significantly higher rate of facet joint violation than that of tinavi group (P < 0.05), and the screws were placed closer to the anterior cortex (P < 0.05). Significantly more intraoperative fluoroscopies were performed in the tinavi group than in the navigation group, and the operation time was significantly longer in the tinavi group than in the navigation group (P < 0.05). The time of single nail implantation, intraoperative blood loss and incision length in navigation group were significantly longer than those in tinavi group. There were no statistically significant differences in other indicators between the two groups (P > 0.05). We come to the following conclusion. The Stealth Station S8 navigation system (Medtronic, USA), which also uses an optical tracking system, and the Tinavi Orthopedic robot have shown the same high accuracy and satisfactory clinical results in the treatment of upper cervical instability. Although the S8 navigation system still has many limitations, it still has good application prospects and is a new tool for spine surgery.