Foraminoplasty Performed with a Trephine and a New Tool in Transforaminal Endoscopic Lumbar Discectomy: A Single-Center Retrospective Study.

OBJECTIVE: Foraminoplasty is an important step in transforaminal endoscopic lumbar discectomy (TELD). A trephine is widely used in foraminoplasty. However, foraminoplasty using a trephine alone sometimes fails to remove the resected bone, resulting in the bone remaining in the foramen or spinal canal, which can potentially cause neurological irritation or injury. The objective of this study is to introduce a self-designed tool, referred to as an anchoring drill, for use with a trephine in foraminoplasty in TELD and to evaluate its advantages. METHODS: A retrospective review was performed to identify patients who underwent L4-5 TELD between January 2019 to January 2022. Foraminoplasty was performed in all patients. Depending on whether the anchoring drill was used or not, patients were divided into two groups. Surgery-related parameters and complications were reviewed. Visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) scores were also assessed for all patients. SPSS statistical software was used for statistical calculation. RESULTS: A total of 100 patients were included (55 in the anchoring drill group and 45 in the trephine group). The incidence of residual bone fragments after foraminoplasty of the anchoring drill group was 9.09%, which was lower than that of the trephine group, at 33.33% (p < 0.05). The mean endoscopic operation time of the anchoring drill group was shorter than that of the trephine group (p < 0.05). The mean fluoroscopy time and duration of foraminoplasty showed no significant differences between the two cohorts. The total perioperative complication incidence was lower in the anchoring drill group, in which the neural irritation incidence showed a significant difference (anchoring drill group: 3.64%, trephine group: 17.78%, p < 0.05). VAS and JOA scores were significantly improved after the operation for all patients (p < 0.001), however, no statistical differences were found between the two groups at each follow-up visit. CONCLUSION: The combination of a trephine with an anchor drill was demonstrated to be safe and effective in foraminoplasty in TELD, improving the success rate of foraminoplasty and reducing neurological complications compared to using trephine alone.

Dry and wet experiments reveal diagnostic clustering and immune landscapes of cuproptosis patterns in patients with ankylosing spondylitis.

Cuproptosis is a new manner of mitochondrial cell death induced by copper. There is evidence that serum copper has a crucial impact on ankylosing spondylitis (AS) by copper-induced inflammatory response. However, the molecular mechanisms of cuproptosis modulators in AS remain unknown. We aimed to use a bioinformatics-based method to comprehensively investigate cuproptosis-related subtype identification and immune microenvironment infiltration of AS. Additionally, we further verified the results by in vitro experiments, in which peripheral blood and fibroblast cells from AS patients were used to evaluate the functions of significant cuproptosis modulators on AS. Finally, eight significant cuproptosis modulators were identified by analysis of differences between controls and AS cases from GSE73754 dataset. Eight prognostic cuproptosis modulators (LIPT1, DLD, PDHA1, PDHB, SLC31A1, ATP7A, MTF1, CDKN2A) were identified using a random forest model for prediction of AS risk. A nomogram model of the 8 prognostic cuproptosis modulators was then constructed; the model could be beneficial in clinical settings, as indicated by decision curve analysis. Consensus clustering analysis was used to divide AS patients into two cuproptosis subtypes (clusterA & B) according to significant cuproptosis modulators. The cuproptosis score of each sample was calculated by principal component analysis to quantify cuproptosis subtypes. The cuproptosis scores were higher in clusterB than in clusterA. Additionally, cases in clusterA were closely associated with the immunity of activated B cells, Activated CD4 T cell, Type17 T helper cell and Type2 T helper cell, while cases in clusterB were linked to Mast cell, Neutrophil, Plasmacytoid dendritic cell immunity, indicating that clusterB may be more correlated with AS. Notably, key cuproptosis genes including ATP7A, MTF1, SLC31A1 detected by RT-qPCR with peripheral blood exhibited significantly higher expression levels in AS cases than controls; LIPT1 showed the opposite results; High MTF1 expression is correlated with increased osteogenic capacity. In general, this study of cuproptosis patterns may provide promising biomarkers and immunotherapeutic strategies for future AS treatment.

Unravelling diagnostic clusters and immune landscapes of cuproptosis patterns in intervertebral disc degeneration through dry and wet experiments.

Cuproptosis is a manner of mitochondrial cell death induced by copper. However, cuproptosis modulators' molecular processes in intervertebral disc degeneration (IDD) are still unclear. To better understand the processes of cuproptosis regulators in IDD, a thorough analysis of cuproptosis regulators in the diagnostic biomarkers and subtype determination of IDD was conducted. Then we collected clinical IDD samples and successfully established IDD model in vivo and in vitro, and carried out real-time quantitative polymerase chain reaction (RT-qPCR) validation of significant cuproptosis modulators. Totally we identified 8 crucial cuproptosis regulators in the present research. Using a random forest model, we isolated 8 diagnostic cuproptosis modulators for the prediction of IDD risk. Then, based on our following decision curve analysis, we selected the five diagnostic cuproptosis regulators with importance scores greater than two and built a nomogram model. Using a consensus clustering method, we divided IDD patients into two cuproptosis clusters (clusterA and clusterB) based on the important cuproptosis regulators. Additionally, each sample's cuproptosis value was evaluated using principal component analysis in order to quantify the cuproptosis clusters. Patients in clusterB had higher cuproptosis scores than patients in clusterA. Moreover, we found that clusterB was involved in the immunity of natural killer cell, while clusterA was related to activated CD4 T cell, activated B cell, etc. Notably, cuproptosis modulators detected by RT-qPCR showed generally consistent expression levels with the bioinformatics results. To sum up, cuproptosis modulators play a crucial role in the pathogenic process of IDD, providing biomarkers and immunotherapeutic approaches for IDD.

Potential molecular targets and drugs for basement membranes-related intervertebral disk degeneration through bioinformatics analysis and molecular docking.

BACKGROUND: Through bioinformatics analysis to identify the hub genes of Intervertebral disc degeneration (IVDD) associated with basement membranes (BMs) and find out the potential molecular targets and drugs for BMs-related annulus fibrosus (AF) degeneration based on bioinformatic analysis and molecular approach. METHODS: Intervertebral disc degeneration (IVDD) related targets were obtained from GeneCards, DisGenet and OMIM databases. BMs related genes were obtained from Basement membraneBASE database. The intersection targets were identified and subjected to protein-to-protein interaction (PPI) construction via STRING. Hub genes were identified and conducted Gene ontology (GO) and pathway enrichment analysis through MCODE and Clue GO in Cytospace respectively. DSigDB database was retrieved to predict therapeutic drugs and molecular docking was performed through PyMOL, AutoDock 1.5.6 to verify the binding energy between the drug and the different expressed hub genes. Finally, GSE70362 from GEO database was obtained to verify the different expression and correlation of each hub gene for AF degeneration. RESULTS: We identified 41 intersection genes between 3 disease targets databases and Basement membraneBASE database. PPI network revealed 25 hub genes and they were mainly enriched in GO terms relating to glycosaminoglycan catabolic process, the TGF-ß signaling pathway. 4 core targets were found to be significant via comparison of microarray samples and they showed strong correlation. The molecular docking results showed that the core targets have strong binding energy with predicting drugs including chitosamine and retinoic acid. CONCLUSIONS: In this study, we identified hub genes, pathways, potential targets, and drugs for treatment in BMs-related AF degeneration and IVDD.

Endoscopic Resection and Decompression for Lateral Displacement of Cage after Oblique Lumbar Interbody Fusion: A Case Report from a Single Center.

BACKGROUND: Lateral displacement of cage is a rarely seen complication of oblique lumbar interbody fusion (OLIF). To the best of our knowledge, this complication has always been revised with posterior open surgery. However, open surgery often associates with large trauma and long period of recovery. CASE PRESENTATION: In the case presented, a 64-year-old male patient with lateral displacement of cage which consequently caused neurological symptoms after OLIF, was reported and surgically revised with an endoscopic resection and decompression technique. The surgery was performed through a posterolateral approach which was similar to transforaminal approach, with estimated blood loss of 45mL and whole operation time of 70 min. Neurological symptoms were disappeared after operation immediately and the patient was discharged 2 days later. He reported no symptoms other than mild weakness of the lower back at the last follow-up of 12 months. CONCLUSION: Endoscopic decompression technique may be an effective alternative to surgically treat lateral displacement of cage after OLIF with advantages of minimal invasion and quick recovery.

Psoas Major Swelling Grade Affects the Clinical Outcomes after OLIF: A Retrospective Study of 89 Patients.

OBJECTS: Oblique lumbar interbody fusion (OLIF) has gained increasing popularity recently. However, complications resulting from intraoperative retraction of psoas major (PM) sometimes occur. The aim of this study is to evaluate the degree of PM swelling by developing a scoring system called the Psoas Major Swelling Grade (PMSG), and to investigate the correlation between the PMSG and clinical outcomes after OLIF. METHODS: Patients who underwent L4-5 OLIF at our hospital from May 2019 to May 2021 were reviewed and all data were recorded. The extent of postoperative PM swelling was determined by calculating the percentage of change in the PM area before and after surgery on MRI and divided into three grades subsequently. Swelling within the range of 0% to 25% was defined as grade I, 25%-50% was grade II, and more than 50% was grade III. All patients were grouped into the new grade system and followed up for at least 1 year, during which the visual analog scale (VAS) and Oswestry disability index (ODI) scores were recorded. Categorical data were analyzed using chi-square and Fisher's exact tests, while continuous variables were assessed with one-way ANOVA and paired t-tests. RESULTS: Eighty-nine consecutive patients were enrolled in this study, with a mean follow-up duration of 16.9 months. The proportion of female patients in the PMSG I, II, and III groups was 57.1%, 58.3%, and 84.1%, respectively (p = 0.024).  Furthermore, the total complication rate was 43.2% in the PMSG III group, significantly higher than 9.5% and 20.8% in the PMSG I and II groups (p = 0.012). The incidence of thigh paraesthesia was also considerably higher in the PMSG III group at 34.1% (p = 0.015), compared to 9.5% and 8.3% in the PMSG I and II groups. Among the patients, 12.4% exhibited a teardrop-shaped PM, with the majority (90.9%) belonging to the PMSG III group (p = 0.012). Additionally, the PMSG III group demonstrated a higher estimated blood loss (p = 0.007) and significantly worse clinical scores at the 1-week follow-up assessment (p < 0.001). CONCLUSION: PM swelling adversely affects the OLIF prognosis. Female patients with teardrop-shaped PM are more likely to develop swelling after OLIF. A higher PMSG is associated with a higher complication rate of thigh pain or numbness and worse short-term clinical outcomes.

Clinical Outcomes and Radiologic Parameters of Endoscopic Lumbar Interbody Fusion Using a Novel Nerve Baffle with a Minimum 1-year Follow-up.

OBJECTIVE: Since endoscopic lumbar interbody fusion procedure has established, the insertion of cage requires a large working tube, which may lead to nerve root irritation. A novel nerve baffle was used for endoscopic lumbar interbody fusion (ELIF) and its short-term outcomes were analyzed. METHODS: A total of 62 patients (32 cases in tube group, 30 cases in baffle group) with lumbar degenerative diseases who underwent endoscopic lumbar fusion surgery from July 2017 to September 2021 were retrospectively analyzed. Clinical outcomes were measured using pain visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedic Association Scores (JOA), and complications. Perioperative blood loss was calculated using the Gross formula. Radiologic parameters included lumbar lordosis, surgical segmental lordosis, cage position, and fusion rate. RESULTS: There were significant differences in VAS, ODI, and JOA scores postoperatively, 6 months after operation, and at the last follow-up (P < 0.05) within the 2 groups. The VAS and ODI score and hidden blood loss were significantly lower (P < 0.05) for the baffle group. There was no significant difference in lumbar lordosis and segmental lordosis (P > 0.05). Postoperative disc height was significantly higher than preoperative and follow-up disc heights (P < 0.05) for both groups. There was no statistical difference in fusion rate and cage position parameters or subsidence rate. CONCLUSIONS: Endoscopic lumbar interbody fusion using the novel baffle has more advantages in nerve protection and hidden blood loss reduction than traditional ELIF with working tube. Compared with the working tube procedure, it has similar or even better short-term clinical outcomes.

Hidden Blood Loss and Its Possible Risk Factors in Full Endoscopic Lumbar Interbody Fusion.

BACKGROUND: Full endoscopic lumbar interbody fusion (Endo-LIF) is a representative recent emerging minimally invasive operation. The hidden blood loss (HBL) in an Endo-LIF procedure and its possible risk factors are still unclear. METHODS: The blood loss (TBL) was calculated by Gross formula. Sex, age, BMI, hypertension, diabetes, ASA classification, fusion levels, surgical approach type, surgery time, preoperative RBC, HGB, Hct, PT, INR, APTT, Fg, postoperative mean arterial pressure, postoperative heart rate, Intraoperative blood loss (IBL), patient blood volume were included to investigate the possible risk factors by correlation analysis and multiple linear regression between variables and HBL. RESULTS: Ninety-six patients (23 males, 73 females) who underwent Endo-LIF were retrospective analyzed in this study. The HBL was 240.11 (65.51, 460.31) mL (median [interquartile range]). Fusion levels (p = 0.002), age (p = 0.003), hypertension (p = 0.000), IBL (p = 0.012), PT (p = 0.016), preoperative HBG (p = 0.037) were the possible risk factors. CONCLUSION: Fusion levels, younger age, hypertension, prolonged PT, preoperative HBG are possible risk factors of HBL in an Endo-LIF procedure. More attention should be paid especially in multi-level minimally invasive surgery. The increase of fusion levels will lead to a considerable HBL.

Bioinformatics identification and experimental validation of m6A-related diagnostic biomarkers in the subtype classification of blood monocytes from postmenopausal osteoporosis patients.

Background: Postmenopausal osteoporosis (PMOP) is a common bone disorder. Existing study has confirmed the role of exosome in regulating RNA N6-methyladenosine (m6A) methylation as therapies in osteoporosis. However, it still stays unclear on the roles of m6A modulators derived from serum exosome in PMOP. A comprehensive evaluation on the roles of m6A modulators in the diagnostic biomarkers and subtype identification of PMOP on the basis of GSE56815 and GSE2208 datasets was carried out to investigate the molecular mechanisms of m6A modulators in PMOP. Methods: We carried out a series of bioinformatics analyses including difference analysis to identify significant m6A modulators, m6A model construction of random forest, support vector machine and nomogram, m6A subtype consensus clustering, GO and KEGG enrichment analysis of differentially expressed genes (DEGs) between different m6A patterns, principal component analysis, and single sample gene set enrichment analysis (ssGSEA) for evaluation of immune cell infiltration, experimental validation of significant m6A modulators by real-time quantitative polymerase chain reaction (RT-qPCR), etc. Results: In the current study, we authenticated 7 significant m6A modulators via difference analysis between normal and PMOP patients from GSE56815 and GSE2208 datasets. In order to predict the risk of PMOP, we adopted random forest model to identify 7 diagnostic m6A modulators, including FTO, FMR1, YTHDC2, HNRNPC, RBM15, RBM15B and WTAP. Then we selected the 7 diagnostic m6A modulators to construct a nomogram model, which could provide benefit with patients according to our subsequent decision curve analysis. We classified PMOP patients into 2 m6A subtypes (clusterA and clusterB) on the basis of the significant m6A modulators via a consensus clustering approach. In addition, principal component analysis was utilized to evaluate the m6A score of each sample for quantification of the m6A subgroups. The m6A scores of patients in clusterB were higher than those of patients in clusterA. Moreover, we observed that the patients in clusterA had close correlation with immature B cell and gamma delta T cell immunity while clusterB was linked to monocyte, neutrophil, CD56dim natural killer cell, and regulatory T cell immunity, which has close connection with osteoclast differentiation. Notably, m6A modulators detected by RT-qPCR showed generally consistent expression levels with the bioinformatics results. Conclusion: In general, m6A modulators exert integral function in the pathological process of PMOP. Our study of m6A patterns may provide diagnostic biomarkers and immunotherapeutic strategies for future PMOP treatment.

Different Moro Zones of Psoas Major Affect the Clinical Outcomes after Oblique Lumbar Interbody Fusion: A Retrospective Study of 94 Patients.

Oblique lumbar interbody fusion (OLIF) has been driven to the maturity stage in recent years. However, postoperative symptoms such as thigh paresthesia resulting from intraoperative retraction of the psoas major (PM) have sometimes occurred. The aim of this study was to assess the different positions and morphology of PM muscles and their relationship with clinical outcomes after OLIF by introducing the Moro zones. Patients who underwent L4-5 OLIF at our institution between April 2019 and June 2021 were reviewed and all data were recorded. All patients were grouped by Moro zones into a Moro A cohort and a Moro I and II cohort based on the front edges of their left PM muscles. A total of 94 patients were recruited, including 57 in the Moro A group and 37 in the Moro I and II group. Postoperative thigh pain or numbness occurred in 12 (21.1%) and 2 (5.4%) patients in the Moro A group and the Moro I and II group, respectively. There was no difference in the psoas major transverse diameter (PMTD) between groups preoperatively, while longer PMTD was revealed postoperatively in the Moro A group. The operating window (OW) and psoas major sagittal diameter (PMSD) showed significant differences within and between groups. Thirteen patients had teardrop-shaped PM muscles, with 92.3% in the Moro A group showing significantly worse clinical scores at 1-week follow-up. The Moro zones of the PM affected the short-term outcomes after OLIF. Preoperative measurements and analysis of OW, PMSD and PM morphology should be performed as necessary to predict short-term outcomes.

Endoscopic Revision for Long-Term Symptomatic Cage Retropulsion after TLIF: The Clinical Presentation in a Single Center.

BACKGROUND: Cage retropulsion after transforaminal lumbar interbody fusion (TLIF) is a common complication that is more frequently detected in the early postoperative period. Revision in the early stages is relatively less difficult in symptomatic cases. However, cage retropulsion is quite rare for patients with intervertebral osseous fusion in the long term after TLIF, and there are no relevant reports related to the revision plan. CASE PRESENTATION: Here, we report a case of a patient who underwent L4-S1 TLIF at another hospital 4 years ago, accompanied by recurrent pain and discomfort of the left lower limb after the operation. Due to recent condition aggravation, it was considered to be caused by compression of the nerve root due to cage retropulsion. Nerve root sealing and endoscopy surgery were performed on the operative segment. It was found that cage retropulsion at the L4/5 level was a suspicious focus according to careful analysis of the clinical manifestations of the patient. Selective block of the nerve root on the level resulted in relief of the patient's original symptoms. After the posterior edge of the cage was exposed under the endoscope through an intervertebral foramen approach, the posterior edge of the cage protruding into the spinal canal was removed by high-speed burr grinding, working casing reduction and other methods. Postoperative symptoms of pain in the low back and lower limb were relieved completely. CONCLUSIONS: It is feasible to use the power system to remove the retrograde cage under the endoscope through the intervertebral foramen approach for the revision of symptomatic polyether ether ketone (PEEK) cage retropulsion in the long term after TLIF.

A New Potential Complication in 2-Level Anterior Cervical Discectomy and Fusion with Zero-Profile Devices: Collapse of the Middle Cervical Vertebra.

OBJECTIVE: The objective of this study was to describe a new potential complication, collapse in the middle cervical vertebra of consecutive 2-level anterior cervical discectomy and fusion (ACDF), and discuss its possible mechanism. METHODS: Clinical and radiologic outcome data from 27 consecutive 2-level ACDF patients using zero-profile devices were collected at 1, 3, 6, and 12 months postoperatively, as well as the last follow-up. Dysphagia was assessed using the Bazaz score, and clinical outcomes were analyzed using the neck disability index and Japanese Orthopaedic Association score. Radiographic evaluation included measurements of the overall and surgical segment curvature, identification of collapse, and assessment of the ratio of anterior height and wedge of the upper, middle, and lower vertebrae in the surgical segment. RESULTS: The application of zero-profile devices to treat consecutive 2-level cervical spondylosis mostly resulted in good midterm clinical outcomes. Surprisingly, as evidenced by the significantly decreased anterior height and wedge ratio of the middle cervical vertebra, collapse was noted immediately in the middle vertebra in 4 patients at 1 month (n = 3) and 3 months (n = 1). The collapse increased for no more than 6 months, and there was no deterioration of clinical and radiological outcomes at the last follow-up. CONCLUSIONS: Collapse in the middle cervical vertebra of consecutive 2-level ACDF with the application of zero-profile devices can occur in the early postoperative period, which may be due to axial stress concentration and blood supply damage in the middle cervical vertebral body.

Effect of the In Situ Screw Implantation Region and Angle on the Stability of Lateral Lumbar Interbody Fusion: A Finite Element Study.

OBJECTIVE: To investigate the effect of the in situ screw implantation region and angle on the stability of lateral lumbar interbody fusion (LLIF) from a biomechanical perspective. METHODS: A validated L2-4 finite element (FE) model was modified for simulation. The L3-4 fused segment undergoing LLIF surgery was modeled. The area between the superior and inferior edges and the anterior and posterior edges of the vertebral body (VB) is divided into four zones by three parallel lines in coronal and horizontal planes. In situ screw implantation methods with different angles based on the three parallel lines in coronal plane were applied in Models A, B, and C (A: parallel to inferior line; B: from inferior line to midline; C: from inferior line to superior line). In addition, four implantation methods with different regions based on the three parallel lines in horizontal plane were simulated as types 1-2, 1-3, 2-2, and 2-3 (1-2: from anterior line to midline; 1-3: from anterior line to posterior line; 2-2: parallel to midline; 2-3: from midline to posterior line). L3-4 ROM, interbody cage stress, screw-bone interface stress, and L4 superior endplate stress were tracked and calculated for comparisons among these models. RESULTS: The L3-4 ROM of Models A, B, and C decreased with the extent ranging from 47.9% (flexion-extension) to 62.4% (lateral bending) with no significant differences under any loading condition. Types 2-2 and 2-3 had 45% restriction, while types 1-2 and 1-3 had 51% restriction in ROM under flexion-extension conditions. Under lateral bending, types 2-2 and 2-3 had 70.6% restriction, while types 1-2 and 1-3 had 61.2% restriction in ROM. Under axial rotation, types 2-2 and 2-3 had 65.2% restriction, while types 1-2 and 1-3 had 59.3% restriction in ROM. The stress of the cage in types 2-2 and 2-3 was approximately 20% lower than that in types 1-2 and 1-3 under all loading conditions in all models. The peak stresses at the screw-bone interface in types 2-2 and 2-3 were much lower (approximately 35%) than those in types 1-2 and 1-3 under lateral bending, while no significant differences were observed under flexion-extension and axial rotation. The peak stress on the L4 superior endplate was approximately 30 MPa and was not significantly different in all models under any loading condition. CONCLUSIONS: Different regions of entry-exit screws induced multiple screw trajectories and influenced the stability and mechanical responses. However, different implantation angles did not. Considering the difficulty of implantation, the ipsilateral-contralateral trajectory in the lateral middle region of the VB can be optimal for in situ screw implantation in LLIF surgery.

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking.

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes (p < 0.05), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways (p < 0.05), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets' active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets' expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.

Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress.

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis (P < 0.05), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included (P < 0.05), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3-9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.