RNA sequencing-based approaches to identifying disulfidptosis-related diagnostic clusters and immune landscapes in osteoporosis.

Disulfidptosis, a newly recognized cell death triggered by disulfide stress, has garnered attention for its potential role in osteoporosis (OP) pathogenesis. Although sulfide-related proteins are reported to regulate the balance of bone metabolism in OP, the precise involvement of disulfidptosis regulators remains elusive. Herein, leveraging the GSE56815 dataset, we conducted an analysis to delineate disulfidptosis-associated diagnostic clusters and immune landscapes in OP. Subsequently, vertebral bone tissues obtained from OP patients and controls were subjected to RNA sequencing (RNA-seq) for the validation of key disulfidptosis gene expression. Our analysis unveiled seven significant disulfidptosis regulators, including FLNA, ACTB, PRDX1, SLC7A11, NUBPL, OXSM, and RAC1, distinguishing OP samples from controls. Furthermore, employing a random forest model, we identified four diagnostic disulfidptosis regulators including FLNA, SLC7A11, NUBPL, and RAC1 potentially predictive of OP risk. A nomogram model integrating these four regulators was constructed and validated using the GSE35956 dataset, demonstrating promising utility in clinical decision-making, as affirmed by decision curve analysis. Subsequent consensus clustering analysis stratified OP samples into two different disulfidptosis subgroups (clusters A and B) using significant disulfidptosis regulators, with cluster B exhibiting higher disulfidptosis scores and implicating monocyte immunity, closely linked to osteoclastogenesis. Notably, RNA-seq analysis corroborated the expression patterns of two disulfidptosis modulators, PRDX1 and OXSM, consistent with bioinformatics predictions. Collectively, our study sheds light on disulfidptosis patterns, offering potential markers and immunotherapeutic avenues for future OP management.

Comparison of safety and efficacy of posterior lumbar interbody fusion (PLIF) and modified transforaminal lumbar interbody fusion (M-TLIF) in the treatment of single-segment lumbar degenerative diseases.

OBJECTIVE: To compare modified transforaminal lumbar interbody fusion (M-TLIF) with posterior lumbar interbody fusion (PLIF) in the treatment of single-segment lumbar degenerative disorders in order to assess its safety and effectiveness. METHODS: From January 2016 to January 2021, 74 patients who received single-segment M-TLIF were examined. A total of 74 patients having single-segment PLIF during the same time period were included in a retrospective controlled study using the same inclusion and exclusion criteria. The two groups were compared in terms of the fusion rate, the Oswestry disability index (ODI), the visual analogue scale of low back pain (VAS), the perioperative condition, the postoperative complications, and the postoperative neighbouring segment degeneration. RESULTS: All patients had surgery satisfactorily and were monitored for at least a year afterwards. The baseline values for the two groups did not significantly differ. The interbody fusion rate between PLIF (98.65%) and M-TLIF (97.30%) was not significantly different. In the follow-up, the M-TLIF group's VAS score for low back and leg pain was lower than that of the PLIF group. The ODI score of the M-TLIF group was lower than that of the PLIF group at 7 days and 3 months following surgery. Both groups' post-op VAS and ODI scores for low back and leg pain were much lower than those from before the procedure. In M-TLIF group, the operation time, drainage tube extraction time, postoperative bed rest time and hospital stay time were shorter, and the amount of intraoperative blood loss was less. Compared with those before operation, the height of intervertebral space and intervertebral foramen were significantly increased in both groups during postoperative follow-up (P < 0.05). The postoperative complications and adjacent segment degeneration of M-TLIF were significantly lower than those of PLIF. CONCLUSIONS: M-TLIF is a safe and effective treatment for lumbar degenerative disorders, with a high fusion rate and no significant difference between M-TLIF and PLIF. M-TLIF's efficacy and safety are comparable to that of PLIF, particularly in terms of early relief of low back pain and improvement in quality of life following surgery. Therefore, M-TLIF technology can be popularized and applied in clinic.

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.

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.

Synthesis of Trifluoromethylated γ-Lactams through Radical Cascades of N-Cyano Alkenes with CF3SO2Na.

We report herein a facile strategy to synthesize trifluoromethylated γ-lactams through trifluoromethylcarbonylation of N-cyano alkenes using readily available CF3SO2Na as the CF3 radical source. A range of trifluoromethyl-containing γ-lactams was obtained in good yields. This transition-metal-free protocol is demonstrated with mild conditions, broad substrate scope, good functional group tolerance, convenient reagents, and an easy-to-handle operating system.

Investigating the mechanical effect of the sagittal angle of the cervical facet joint on the cervical intervertebral disc.

Background: Facet tropism is defined as the asymmetry between the left and right facet joints relative to the sagittal plane. Published clinical studies have found that facet tropism is associated with cervical disc herniation. However, the relationship between the facet orientation and the side of cervical disc herniation remains controversial. Therefore, this study used the finite-element technique to investigate the biomechanical effects of the sagittal angle of the cervical facet joints on the cervical intervertebral disc. Objective: The biomechanical effects of the sagittal angle of the cervical facet joint on the cervical disc and facet joint were investigated using the finite-element technique. Methods: The finite-element model was constructed using computed tomography scans of a 26-year-old female volunteer. First, a cervical model was constructed from C3 to C7. The model was verified using data from previously published studies. Second, the facet orientation at the C5-C6 level was altered to simulate different sagittal angles of cervical facet joints. Five models, F70, F80, F90, F100, and F110, were simulated with different facet joint orientations (70°, 80°, 90°, 100°, and 110° facet joint angles at the left side, respectively, and 90° facet joint angles at the right side) at the C5-C6 facet joints. In each model, annular fibres stress and facet cartilage pressure were studied under six pure moments and two combined moments. Results: Comparing the stress of the annulus fibres in flexion combined with right axial rotation and in flexion combined with left axial rotation in the same model, no difference in the maximum stress of the annulus fibres was noted between these two different moments in the F90 model, whereas differences of 12.80%, 8.84%, 14.95% and 33.32% were noted in the F70, F80, F100 and F110 models, respectively. The same trend was observed when comparing the maximum stress of the annulus fibres in each model during left and right axial rotation. No differences in annular fibres stress and facet cartilage pressure were noted among the five models in flexion, extension, lateral bending, left axial rotation, and flexion combined with left axial rotation in this study. However, compared with the F70 model in flexion combined with right axial rotation, the annulus fibres stress of the F80, F90, F100, and F110 models increased by 5.53%, 13.03%, 35.04%, and 72.94%, respectively, and the pressure of the left facet joint of these models decreased by 5.65%, 12.10%, 18.41%, and 25.74%, respectively. The same trend was observed in the right axial moment. Conclusion: Facet tropism leads to unbalanced stress distribution on the annulus fibres at the cervical intervertebral disc. The greater the sagittal angle of the facet joint, the greater the annular fibres stress on this side. We hypothesised that the side with the larger sagittal angle of the facet joint exhibits a greater risk of disc herniation.

[Risk factors of hidden blood loss in percutaneous vertebral augmentation].

OBJECTIVE: To explore the risk factors of hidden blood loss in osteoporosis vertebral compression fractures during percutaneous vertebral augmentation. METHODS: From October 2018 to December 2019, 360 patients with osteoporosis vertebral compression fractures who received percutaneous vertebral augmentation were enrolled in this study. The factors analyzed included gender, age, surgical methods, disease course, height, weight, the operative segment, bone mineral density, amount of bone cement, operative time, percentage of height loss, percentage of vertebral height restoration, cement leakage, blood clotting function, preoperative and postoperative hemoglobin and hematocrit and other internal diseases. Total blood loss was calculated by Gross's formula, influential factors of the hidden blood loss were further analyzed by t-test, multivariate linear regression and one-way ANOVA analysis. RESULTS: Surgical methods, the operative segment, disease course, cement leakage, preoperative hemoglobin, cement leakage via the basivertebral and segmental vein were significantly correlated with hidden blood loss(P<0.05). CONCLUSION: Patients with percutaneous kyphoplasty, two-level and multi-level surgery, the course of the disease beyond 6 weeks, cement leakage via the basivertebral and segmental vein, and lower preoperative hemoglobin had more perioperative hidden blood loss.

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.

Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy.

Objective: This study proposes to explore the protective effect of Zuo-Gui-Wan (ZGW) aqueous extract on spinal glucocorticoid-induced osteoporosis (GIOP) in vivo and in vitro, and the underlying mechanisms of ZGW in GIOP and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) were conducted. Methods: In vivo, SD rats were randomly divided into three groups: control group (CON), dexamethasone (DEXM) group, and ZGW group, which were given vehicle, DEXM injection, and ZGW intragastric administration at the same time. Vertebral bone microarchitecture, biomechanics, histomorphology, serum AKP activity, and the autophagosome of osteoblasts were examined. The mRNA expressions of let-7f, autophagy-associated genes (mTORC1, Beclin-1, ATG12, ATG5, and LC3), Runx2, and CTSK were examined. In vitro, the let-7f overexpression/silencing vector was constructed and transfected to evaluate the osteogenic differentiation of BMSCs. Western blot was employed to detect the expression of autophagy-associated proteins (ULK2, ATG5, ATG12, Beclin-1, LC3). Results: In vivo, ZGW promoted the bone quantity, quality, and strength; alleviated histological damage; increased the serum AKP activity; and reduced the autophagosome number in osteoblasts. Moreover, ZGW increased the let-7f, mTORC1, and Runx2 mRNA expressions and reduced the Beclin-1, ATG12, ATG5, LC3, and CTSK mRNA expressions. In vitro, bioinformatics prediction and dual luciferase reporter gene assay verified that let-7f targeted the binding to ULK2 and negatively regulated the ULK2 expression. Furthermore, by let-7f overexpression/silencing, ZGW may promote osteoblast differentiation of BMSCs by regulating let-7f and autophagy as evidenced by Western blot (ULK2, ATG5, ATG12, Beclin-1, LC3). Conclusions: ZGW may ameliorate GC-induced spinal osteoporosis by promoting osteoblast differentiation of BMSCs by activation of let-7f and suppression of autophagy.

Lumbar posterior group muscle degeneration: Influencing factors of adjacent vertebral body re-fracture after percutaneous vertebroplasty.

Objective: The purpose of the study was to explore the influencing factors of adjacent vertebral re-fracture after percutaneous vertebroplasty (PVP) for osteoporosis vertebral compression fractures (OVCFs). Methods: We retrospectively analyzed the clinical data of 55 patients with adjacent vertebral re-fracture after PVP operation for OVCFs in our hospital from January 2016 to June 2019, they were followed up for 1 year and included in the fracture group. According to the same inclusion and exclusion criteria, we collected the clinical data of 55 patients with OVCFs without adjacent vertebral re-fracture after PVP in the same period and included them in the non-fracture group. We performed univariate and multivariate logistic regression analysis on the influencing factors of adjacent vertebral re-fracture in patients with OVCFs after PVP. Results: There were significant differences in body mass index (BMI), bone mineral density (BMD) T-value, amount of bone cement injected, bone cement leakage, history of glucocorticoid use, cross-sectional area (CSA), cross-sectional area asymmetry (CSAA), fat infiltration rate (FIR), and fat infiltration rate asymmetry (FIRA) of lumbar posterior group muscles [multifidus (MF) and erector spinae (ES)] between the two groups (p < 0.05). There was no significant difference in sex, age, or time from the first fracture to operation, the CAS, CSAA, FIR, and FIRA of psoas major (PS) between the two groups (p > 0.05). Multivariate logistic regression showed that a higher dose of bone cement, greater CSAA and FIR of multifidus, and higher CSAA of erector spinae were independent risk factors for recurrent fractures of adjacent vertebrae after PVP. Conclusion: There are many risk factors for recurrent vertebral fracture after PVP in patients with OVCFs, and degeneration of paraspinal muscles (especially posterior lumbar muscles) may be one of the risks.

Clinical efficacy of general anesthesia versus local anesthesia for percutaneous transforaminal endoscopic discectomy.

Objective: Local anesthesia (LA) is recommended for percutaneous transforaminal endoscopic discectomy(PTED), but satisfactory pain management is not mostly achieved. The goal of this study was to examine the clinical efficacy of PTED for lumbar disc herniation when performed under local anaesthetic vs. general anesthesia (GA). Methods: From August 2018 to August 2020, the clinical data of 108 patients treated with PTED were retrospectively evaluated and separated into two groups: LA and GA based on the anesthesia method. General information and clinical outcomes of patients were included. Visual analog scale (VAS) and Oswestry disability index (ODI) were recorded before operation, 1 week after operation, and 1 year after operation. In addition, VAS for back pain and leg pain on the second postoperative day were also recorded. Results: We divided the patients into two groups: 72 in LA and 36 in GA. There were no significant differences in gender, age, course of disease, body mass index, surgical segment, duration of operation, intraoperative bleeding, time of fluoroscopy, length of hospital stay, total hospitalization cost reoperation, surgical satisfaction, Macnab satisfaction, complications, preoperative and 1 year postoperatively VAS for back pain and leg pain and ODI, VAS for leg pain on the second day and 1 week postoperatively between the two groups (P > 0.05). VAS for back pain in GA group on the second day postoperatively, as well as the VAS for back pain and ODI at one week postoperatively, were better than those in LA group (P < 0.05). However, the total hospitalization cost in LA group was significantly lower than that in GA group (P < 0.05). Further analysis of different ages in the two groups showed that there were significant differences in the VAS for back pain on the second day postoperatively and ODI at 1 week postoperatively in the middle-aged group (45 ≤ Y ≤ 59), as well as the VAS for back pain on the second day postoperatively in the senior group (Y ≥ 60) (P < 0.05). However, there were no significant difference among other groups (P > 0.05). Conclusion: Long-term outcomes were similar for both PTED under LA and GA, while GA group had better short-term outcomes, especially in middle-aged and elderly patients.

Copper-Catalyzed Direct Cycloaddition of Imidazoles and Alkenes to Trifluoromethylated Tricyclic Imidazoles.

We reported herein a copper-catalyzed trifluoromethylarylated cycloaddition of imidazoles and olefins using CF3SO2Cl as the radical source to synthesize highly functionalized tricyclic imidazoles. This procedure exhibits a wide range of substrate scope with 25%-93% isolated yields (36 examples). Mechanistic studies were carried out to support a free trifluoromethyl radical pathway.