Assessing the causal relationship between blood metabolites and low back pain: a Mendelian randomization study.

AIM: Low back pain (LBP) is one of the most common health problems worldwide. This study aimed to determine whether blood metabolites were causally linked to the risk of LBP. METHODS: Based on summary-level genome-wide association studies, we designed a Mendelian randomization (MR) study. Instrumental variables were selected for each blood metabolite with the following criteria: genome-wide significance levels of < 5e-8 and independent clumping (r2 < 0.001, distance < 10,000 kb). Inverse-variance weighting (IVW) was used as the primary statistical method. The weighted median (WM) method and MR-Egger regression were implemented to complement IVW. Subsequently, sensitivity analyses were conducted, including Cochran's Q test, MR-Egger intercept analysis, scatter plots, leave-one-out analysis, and funnel plots. RESULTS: IVW revealed that higher levels of lactate (odds ratio [OR] = 0.974, 95% confidence interval [CI] 0.953-0.995, P = 0.017), medium low-density lipoprotein triglycerides (OR = 0.990, 95% CI 0.983-0.997, P = 0.005) and albumin (OR = 0.985, 95% CI 0.973-0.998, P = 0.019) had a causal effect on decreased risk of LBP, whereas positive causality was detected between genetic predisposition to tyrosine and LBP (OR = 1.016, 95% CI 1.001-1.032, P = 0.043). Estimates from WM and MR-Egger were consistent with the direction of the IVW method. Additionally, there was no evidence of heterogeneity or pleiotropy in this study. CONCLUSION: This MR study demonstrated that four blood metabolites were causally related to LBP. It is possible to enhance the diagnosis of LBP, prognostic outcome predictions, and the personalization of therapy by analyzing novel signatures of metabolites.

Identification of blood metabolites linked to the risk of intervertebral disc diseases: a comprehensive Mendelian randomization study.

BACKGROUND: Intervertebral disc degeneration (IVDD) has affected millions of people worldwide and dramatically affects human beings' quality of life. Observational studies hypothesize that metabolites play key roles as markers and effectors of IVDD, but their causality has not yet been illustrated. METHODS: We conducted comprehensive Mendelian randomization (MR) to determine the causal relationship between 249 plasma metabolites and IVDD. Inverse-variance weighting was used as the primary estimate, whereas MR-Egger and weighed median were used to detect robustness. A series of sensitivity analyses including Cochran Q test, leave one out, and MR-Egger intercept analysis were also conducted. RESULTS: In total, we found 13 blood metabolites significantly associated with IVDD, including phospholipids in very large high-density lipoprotein (HDL), free cholesterol to total lipids ratio in very large HDL, average diameter for HDL particles, cholesteryl esters to total lipids ratio in large HDL, free cholesterol to total lipids ratio in medium HDL, creatinine, free cholesterol to total lipids ratio in large HDL, phospholipids to total lipids ratio in very large HDL, cholesterol to total lipids ratio in very large HDL, cholesteryl esters to total lipids ratio in large HDL, phospholipids in large HDL, total lipids in very large HDL, and total lipids in large HDL. No pleiotropy was detected. Heterogeneity existed in several estimates and random-effect inverse-variance weighting was applied. CONCLUSIONS: Our study highlighted the causal association of blood metabolites with the risk of IVDD. Our results provide new insights into possible treatment protocols controlling the concentration of specific blood metabolites in IVDD patients. Key messages What is already known on this topic Low back pain is the most common symptom for patients with intervertebral disc degeneration (IVDD) and influences the quality of life of large populations. Observational studies have indicated the association between metabolites and IVDD. However, causality has not been determined yet. What this study adds We conducted a comprehensive Mendelian randomization study to reveal the causal effect from 249 blood metabolites on low back pain. A total of 13 metabolites were found to causally affect the risk of IVDD, among which 11 were negatively associated and 2 were positively asscociated. How this study might affect research, practice, or policy These 13 significant metabolites could serve as biomarkers for IVDD and our results provide new insights into possible treatment protocols for IVDD patients.

[Application of a new point contact pedicle navigation template as an auxiliary screw implant in scoliosis correction surgery].

Objective: To explore the effectiveness of a new point contact pedicle navigation template (referred to as "new navigation template" for simplicity) in assisting screw implantation in scoliosis correction surgery. Methods: Twenty-five patients with scoliosis, who met the selection criteria between February 2020 and February 2023, were selected as the trial group. During the scoliosis correction surgery, the three-dimensional printed new navigation template was used to assist in screw implantation. Fifty patients who had undergone screw implantation with traditional free-hand implantation technique between February 2019 and February 2023 were matched according to the inclusion and exclusion criteria as the control group. There was no significant difference between the two groups ( P>0.05) in terms of gender, age, disease duration, Cobb angle on the coronal plane of the main curve, Cobb angle at the Bending position of the main curve, the position of the apical vertebrae of the main curve, and the number of vertebrae with the pedicle diameter lower than 50%/75% of the national average, and the number of patients whose apical vertebrae rotation exceeded 40°. The number of fused vertebrae, the number of pedicle screws, the time of pedicle screw implantation, implant bleeding, fluoroscopy frequency, and manual diversion frequency were compared between the two groups. The occurrence of implant complications was observed. Based on the X-ray films at 2 weeks after operation, the pedicle screw grading was recorded, the accuracy of the implant and the main curvature correction rate were calculated. Results: Both groups successfully completed the surgeries. Among them, the trial group implanted 267 screws and fused 177 vertebrae; the control group implanted 523 screws and fused 358 vertebrae. There was no significant difference between the two groups ( P>0.05) in terms of the number of fused vertebrae, the number of pedicle screws, the pedicle screw grading and accuracy, and the main curvature correction rate. However, the time of pedicle screw implantation, implant bleeding, fluoroscopy frequency, and manual diversion frequency were significantly lower in trial group than in control group ( P<0.05). There was no complications related to screws implantation during or after operation in the two groups. Conclusion: The new navigation template is suitable for all kinds of deformed vertebral lamina and articular process, which not only improves the accuracy of screw implantation, but also reduces the difficulty of operation, shortens the operation time, and reduces intraoperative bleeding.

Repair of spinal cord injury in rats via exosomes from bone mesenchymal stem cells requires sonic hedgehog.

OBJECTIVE: The loss of neural ability leading to subsequent diminishing of motor function and the impairment below the location of the injury is a result of the SCI (Spinal Cord Injury). Among the many therapeutic agents for SCI, the exosomes considered as extracellular vesicles seem to be the most promising. Sonic Hedgehog (Shh) is an exosome-carrying protein. This Study's purpose was to identify whether Shh is required for exosomes from BMSCs (mesenchymal stem cells of the bone) and plays a protective effect on SCI. METHODS: Spinal cord injection with shRNA Shh-adeno associated virus (sh-Shh-AAV) were used to silence Shh. Exosomes were extracted from BMSCs. Rats that had suffered SCI were given intravenous injections of exosomes through the veins of the tail. Immunohistochemistry was used to identify the expression of Shh glycoprotein molecule as well as the expression of Gli-1 (glioma-associated oncogene homolog 1) in the rat spinal cord tissues. Western blot was performed to measure the levels of growth associated protein-43 (GAP-43). The BBB (Basso Beattie Bresnahan) score was used to assess the motor functions of the hind legs. In the same manner, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling or TUNEL and Nissl Staining was deployed to assess the level of regeneration of neurons and assess the level of histopathological damage in the tissues of the Spinal Cord. RESULTS: In the case of the rats with SCI, the levels of display of Gli-1 and Shh showed dramatic improvement after the BMSCs exosome injections. In comparison to rats with SCI, the subjects of BMSCs exosomes group showed an improvement in their SCI, including a higher BBB score and Nissl body count, increasing GAP-43 expression, along with a much-decreased number of cells that suffered apoptosis. While the exosome effect on Spinal Cord Injury was completely ineffective in rats that had Shh silencing. CONCLUSIONS: Exosomes secreted from BMSCs showed great effectiveness in the SCI healing with a vital involvement of Shh in this repair.

Exosomes secreted from sonic hedgehog-modified bone mesenchymal stem cells facilitate the repair of rat spinal cord injuries.

BACKGROUND: Spinal cord injuries (SCIs) can cause a loss of neurons and associated sensory and motor functionality below the injured site. No approaches to treating SCIs in humans have been developed to date. Exosomes are extracellular vesicles that hold promise as a potential therapeutic modality when treating such injuries. The present study was thus designed to determine whether sonic hedgehog (Shh)-overexpressing bone mesenchymal stem cell (BMSC)-derived exosomes were protective in the context of SCIs. METHODS: Exosomes were extracted from control or Shh lentivirus-transduced BMSCs, yielding respective BMSC-Exo and BMSC-Shh-Exo preparations which were intravenously injected into SCI model rats. Shh expression in spinal cord tissues in these animals was then assessed via immunohistochemical staining, while Basso-Beattie-Bresnahan (BBB) scores were utilized to measure high limb motor function. Neuronal damage and regeneration within the spinal cord were additionally evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Nissl, hematoxylin and eosin, and immunofluorescent staining. RESULTS: Both BMSC-Exo and BMSC-Shh-Exo preparations significantly increased Shh expression in the spinal cord of SCI model rats and improved BBB scores in these treated animals, while also increasing the frequencies of Nissl- and NeuN-positive neurons are reducing the numbers of apoptotic and GFAP-positive neurons. While both treatments yielded some degree of benefit to treated animals relative to untreated controls, BMSC-Shh-Exos were more beneficial than were control BMSC-Exos. CONCLUSIONS: Shh-overexpressing BMSC-derived exosomes represent an effective treatment that can facilitate SCI repair in rats.

[EFFECTIVENESS OF KNEE EXTENSOR MECHANISM RECONSTRUCTION FOR RECURRENT PATELLAR SUBLUXATION WITH BONE ANCHOR IN ADOLESCENTS].

OBJECTIVE: To explore the effectiveness of knee extensor mechanism reconstruction in the treatment of recurrent patellar subluxation with bone anchor in adolescents. METHODS: Between January 2010 and December 2013, 20 patients with patellar subluxation were treated by knee extensor mechanism reconstruction with bone anchor. There were 11 males and 9 females, aged from 12 to 17 years (mean, 15.3 years). The left knee was involved in 12 cases and the right knee in 8 cases. The disease duration was 5-10 years (mean, 7 years). All the patients had knee pain and lateral subluxation of the patella. Preoperative Lysholm knee score was 71.4 ± 4.7. All the patients received the MRI examination to exclude menisci or ligaments lesion. CT examination showed the tibial tuberosity trochlear groove spacing ranged from 15 to 20 mm (mean, 17 mm). X-ray film examination indicated that no varus or valgus was observed, and bony structure was normal. RESULTS: All the incisions healed at first stage. The patients received follow-up of 12-24 months (mean, 13 months). Knee pain occurred in 2 cases and were cured after symptomatic treatment. The axial X-ray films showed good position of the patella and normal anatomic relationship of the patellofemoral joint. No anchor loosening and pulling out, internal fixation failure, pseudoarthrosis formation, and postoperative recurrent patellar subluxation occurred during follow-up. At 1 year, the Lysholm knee score was significantly improved to 94.2 ± 3.4 (t = 22.705, P = 0.000). According to Insall criterion, the results were excellent in 9 cases, good in 9 cases, and fair in 2 cases, with an excellent and good rate of 90%. CONCLUSION: The bone anchor for extensor mechanism reconstruction is a convenient and reliable way to treat the recurrent patellar subluxation, with a satisfactory early effectiveness and less complications; however, its long-term effectiveness is required a further follow-up.