Search

Objective: Disuse osteoporosis is known to be primarily caused by a lack of exercise. However, the causal relationships between zinc and immunity and disuse osteoporosis remain unknown. This study investigated these relationships and their potential mechanisms. Methods: This study was an integrative study combining genome‐wide association studies and transcriptomics. Two‐sample Mendelian randomization analysis (MR) was used to analyze the causal relationships between exposures (zinc, immunity, physical activity) and the outcome (osteoporosis) with the aid of single‐nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Four models, MR‐Egger, inverse variance weighted, weighted median and MR‐Pleiotrophy RESidual Sum and Outlier (MRPRESSO), were used to calculate odds ratio values. Sensitivity and heterogeneity analyses were also performed using MRPRESSO and MR‐Egger methods. The mRNA transcriptomic analysis was subsequently conducted. Zinc metabolism scores were acquired through single‐sample Gene Set Enrichment Analysis algorithms. Stromal scores were obtained using the R Package "estimate" algorithms. Important Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways were also derived through gene set variation analysis. Cytoscape software helped construct the transcription factor (TF)–mRNA–microRNA (miRNA) network. Virtual screening and molecular docking were performed. Polymerase chain reaction validation was also carried out in vivo. Results: Causal relationships were demonstrated between zinc and exercise (95% confidence interval [CI] = 1.30–2.95, p = 0.001), exercise and immunity (95% CI = 0.36–0.80, p = 0.002), exercise and osteoporosis (95% CI = 0.97–0.99, p = 0.0007), and immunity disorder and osteoporosis (95% CI = 1.30–2.03, p = 0.00002). One hundred and seventy‐nine mRNAs in important modules were screened. Combining the differential expressional genes (DEGs) and the Boruta selection, six DEGs were screened (AHNAK, CSF2, ADAMTS12, SRA1, RUNX2, and SLC39A14). TF HOXC10 and miRNA hsa‐miR‐204 were predicted. Then, the TF–mRNA–miRNA network was successfully constructed. RUNX2 and SLC39A14 were identified as hub mRNAs in the TF–mRNA–miRNA network. Eventually, the novel small drug C6O4NH5 was designed according to the pharmacophore structure of SLC39A14. The docking energy for the novel drug was −5.83 kcal/mol. SLC39A14 and RUNX2 were downregulated (of statistical significance p‐value < 0.05) in our animal experiment. Conclusion: This study revealed that zinc had a protective causal relationship with disuse osteoporosis by promoting exercise and immunity. SLC39A14 and RUNX2 mRNA participated in this zinc‐related mechanism. [ABSTRACT FROM AUTHOR]

Objective: To gain a better understanding of the traumatic mechanism and to develop appropriate treatment for dislocation of the shoulder joint with an ipsilateral humeral shaft fracture. Methods: This was an observational and descriptive study. Nine patients with traumatic shoulder dislocations associated with ipsilateral humeral shaft fractures who visited the emergency room and received treatment from January 2012 to June 2018 were retrospectively analyzed. CT with three‐dimensional reconstruction was performed to provide precise anatomical information of the fractures. The traumatic event and the type of fracture of the humeral shaft were analyzed to help determine the trauma mechanism. Closed reduction of the dislocation was attempted at once under intravenous anesthesia. One patient died the following day due to unrelated causes. All humeral shaft fractures of the eight patients received internal fixation, and then reduction of the dislocation was performed again if previous attempts failed. The affected limb was immobilized in a sling for 3 weeks postoperatively, and then active and passive movement was encouraged. Patients were evaluated based on clinical and radiographic examinations, shoulder joint range of motion, Constant–Murley score, and subjective shoulder value. Results: Four cases in the present study could not give a clear description of the traumatic procedure. The other five patients suffered a second strike on their upper arms when they were hurt, with low mobility and high pain in the shoulder region. Seven cases were simple fractures and two were wedge fractures. According to the AO/OTA classification system, four cases were type 12‐A2, three were type 12‐A3, and two were type 12‐B2. Six patients successfully obtained closed manipulative reduction of the shoulder dislocation in the acute stage. The follow‐up time ranged from 18 to 31 months. No deep wound infections were encountered. All fractures healed uneventfully. The union time ranged from 4 to 6 months. At the final follow‐up, shoulder range‐of‐motion values were found to range from 140° to 170° forward flexion, 30° to 40° extension, 40° to 45° adduction, 150° to 170° abduction, 50° to 60° internal rotation, and 50° to 60° external rotation; no recurrent instability of the shoulder joint occurred; the Constant–Murley score was 89.5 ± 3.7 points (range: 84–94 points); the subjective shoulder value was 89.4% ± 6.3% (range: 75%–95%). Conclusion: Shoulder dislocation most likely occurs first with an axial force or a direct posteroanterior force and a subsequent force results in the shaft fracture. For patients with mid‐distal humerus fractures, closed manipulative reduction of the joint is usually effective. After success of closed reduction, surgery for the humeral shaft fracture is advocated to ensure stability and to make patient nursing convenient. In cases with fractures in the proximal third of the humeral shaft, fixation is suggested beforehand to help reduce the shoulder dislocation. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the biomechanical characteristics of endplate-conformed cervical cages by finite element method ( FEM) analysis and cadaver study. Methods Twelve specimens (C2-C7) and a finite element model (C3-C7) were subjected to biomechanical evaluations. In the cadaver study, specimens were randomly assigned to intact (I), endplate-conformed (C) and non-conformed (N) groups with C4-5 discs as the treated segments. The morphologies of the endplate-conformed cages were individualized according to CT images of group C and the cages fabricated with a 3-D printer. The non-conformed cages were wedge-shaped and similar to commercially available grafts. Axial pre-compression loads of 73.6 N and moment of 1.8 Nm were used to simulate flexion ( FLE), extension ( EXT), lateral bending ( LB) and axial rotation ( AR). Range of motion ( ROM) at C4-5 of each specimen was recorded and film sensors fixed between the cages and C5 superior endplates were used to detect interface stress. A finite element model was built based on the CT data of a healthy male volunteer. The morphologies of the endplate-conformed and wedge-shaped, non-conformed cervical cages were both simulated by a reverse engineering technique and implanted at the segment of C4-5 in the finite element model for biomechanical evaluation. Force loading and grouping were similar to those applied in the cadaver study. ROM of C4-5 in group I were recorded to validate the finite element model. Additionally, maximum cage-endplate interface stresses, stress distribution contours on adjoining endplates, intra-disc stresses and facet loadings at adjacent segments were measured and compared between groups. Results In the cadaver study, Group C showed a much lower interface stress in all directions of motion (all P < 0.05) and the ROM of C4-5 was smaller in FLE- EXT ( P = 0.001) but larger in AR ( P = 0.017). FEM analysis produced similar results: the model implanted with an endplate-conformed cage presented a lower interface stress with a more uniform stress distribution than that implanted with a non-conformed cage. Additionally, intra-disc stress and facet loading at the adjacent segments were obviously increased in both groups C and N, especially those at the supra-jacent segments. However, stress increase was milder in group C than in group N for all directions of motion. Conclusions Endplate-conformed cages can decrease cage-endplate interface stress in all directions of motion and increase cervical stability in FLE- EXT. Additionally, adjacent segments are possibly protected because intra-disc stress and facet loading are smaller after endplate-conformed cage implantation. However, axial stability was reduced in group C, indicating that endplate-conformed cage should not be used alone and an anterior plate system is still important in anterior cervical discectomy and fusion. [ABSTRACT FROM AUTHOR]