Degenerative lumbar spondylolisthesis (DLS) is a major cause of spinal canal stenosis and is often related to lower back pain. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory bone disorders likes intervertebral disc herniation, rheumatoid arthritis (RA), osteoporosis, and bone fracture. IL-19 also acts as a proinflammatory cytokine in RA. The aim of the present study was to investigate whether IL-19 and IL-20 are involved in DLS and compare three different tissues including disc, facet joint, and ligamentum flavum of patients with DLS to verify which tissue is affected more by inflammation. Disc, facet joint and ligamentum flavum from 13 patients with DLS was retrieved, and the expression pattern of IL-19, IL-20, IL-20R1, IL-20R2, TNF-α, IL-1β, and MCP-1 was evaluated using immunohistochemical staining with specific antibodies. The disc cells were isolated and incubated with IL-19 and IL-20 under CoCl2-mimicked hypoxic conditions to analyze the proinflammatory cytokine expression pattern using real-time quantitative PCR with specific primers. IL-19 and IL-20 were positively stained and accompanied by abundant expression of TNF-α, IL-1β, and MCP-1 in facet joints of DLS patients. IL-19 and IL-20’s receptors (IL-20R1 and IL-20R2) were expressed on chondrocytes and fibrocytes/fibroblasts in facet joint and ligamentum flavum tissues from patients with DLS. There was a significant correlation between the expression of IL-20 and IL-1β in facet joint. In vitro assay, IL-19 and IL-20 upregulated the expression of IL-1β, IL-6, TNF-α, IL-8, VEGF, and MCP-1 in primary cultured DLS disc cells under CoCl2-mimicked hypoxic conditions. IL-19, IL-20, and their receptors as well as proinflammatory cytokines (TNF-α, IL-1β, and MCP-1) were expressed more in facet joints than the other tissues in patients with DLS; therefore, the etiology of inflammation might be more facet-centric. IL-19 and IL-20 induced proinflammatory cytokine expression in disc cells and might play a role in the pathogenesis of DLS.

Intervertebral disc (IVD) is an avascular tissue under hypoxic condition after adulthood. Our previous data showed that inflammatory cytokines (interleukin (IL)-1β), IL-20, and bone morphogenetic protein-2 (BMP-2) play important roles in the healing process after disc injury. In the current study, we investigated whether IL-1β, IL-20, or BMP-2 modulate the expression of pro-inflammatory cytokines, chemotaxis factor, and angiogenesis factor on IVD cells under hypoxia. IVD cells were isolated from patients with intervertebral disc herniation (HIVD) at the levels of L4–5 and L5–S1. We found that the expression of IL-1β, IL-20, BMP-2, hypoxia-inducible factor (HIF)-1α, IL-6, IL-8, angiogenetic factor (vascular endothelial growth factor (VEGF)), chemotactic factor (monocyte chemoattractant protein 1 (MCP-1)), and matrix metalloproteinase-3 (MMP-3) was upregulated in IVD cells under hypoxia conditions. In addition, IL-1β upregulated the expression of pro-inflammatory cytokines (IL-6 and IL-8), VEGF, MCP-1, and disc degradation factor (MMP-3) in IVD cells under hypoxia conditions. IL-20 upregulated MCP-1 and VEGF expression. BMP-2 also upregulated the expression of MCP-1, VEGF, and IL-8 in IVD cells under hypoxia conditions. Treatment with antibody against IL-1β decreased VEGF and MMP-3 expression, while treatment with IL-20 or BMP-2 antibodies decreased MCP-1, VEGF, and MMP-3 expression. Moreover, IL-1β modulated both the expression of IL-20 and BMP-2, but IL-20 only modulated BMP-2 either under a hypoxic or normoxic condition. Therefore, we concluded that the inflammation, chemotaxis, matrix degradation, and angiogenesis after disc herniation are influenced by the hypoxic condition and controlled by IL-1β, IL-20, and BMP-2.

Plaster casting has been effective in fracture rehabilitation due to its immobility capability. Thermoplastic casting gains some efficiency and convenience from clinical processing but fitting and immobility are two major tradeoffs. Three-dimensional (3D)-printed braces have demonstrated improvements in innovation, customization, and appearance, but one may question their effectiveness in rehabilitation. Via a science-based data-centric approach, we evaluated the feasibility of customizing 3D-printed braces for wrist fractures after surgery. First, we established a framework for determining a proper timeframe for reliable pressure measurement for plaster casts, devised a method to evaluate the immobilization capability of the plaster casts and customized braces, and assessed changes in immobilization capability due to the clearance adjustment of customized braces. Second, we compared the customized wrist braces and plaster casts in immobilization capability and functional effectiveness in clinical trials. Thirty-three patients were recruited (9, control; 24, experimental). Both the Disability of Arm, Shoulder, and Head, and the Manual Ability Measure surveys showed significant differences between the control and experimental groups after brace wearing time frames of 2, 4, 8, and 12 weeks, and 6 and 12 months. We found that customized braces can match plaster casts in immobilization ability and can promote effective functional recovery.

Despite improvements in cancer treatments resulting in higher survival rates, the proliferation and metastasis of tumors still raise new questions in cancer therapy. Therefore, new drugs and strategies are still needed. Midazolam (MDZ) is a common sedative drug acting through the γ-aminobutyric acid receptor in the central nervous system and also binds to the peripheral benzodiazepine receptor (PBR) in peripheral tissues. Previous studies have shown that MDZ inhibits cancer cell proliferation but increases cancer cell apoptosis through different mechanisms. In this study, we investigated the possible anticancer mechanisms of MDZ on different cancer cell types. MDZ inhibited transforming growth factor β (TGF-β)-induced cancer cell proliferation of both A549 and MCF-7 cells. MDZ also inhibited TGF-β-induced cell migration, invasion, epithelial-mesenchymal-transition, and Smad phosphorylation in both cancer cell lines. Inhibition of PBR by PK11195 rescued the MDZ-inhibited cell proliferation, suggesting that MDZ worked through PBR to inhibit TGF-β pathway. Furthermore, MDZ inhibited proliferation, migration, invasion and levels of mesenchymal proteins in MDA-MD-231 triple-negative breast cancer cells. Together, MDZ inhibits cancer cell proliferation both in epithelial and mesenchymal types and EMT, indicating an important role for MDZ as a candidate to treat lung and breast cancers.

Objective: We assessed our results of short-segment decompression and fixation for osteoporotic thoracolumbar fractures with neurological deficits. Methods: We evaluated 20 elderly patients (age, 60–89 years; mean, 73.2 years) with osteoporotic thoracolumbar fractures and neurological deficits. They underwent short-segment decompression and fixation and followed up for 40.6 (range, 24–68) months. A visual analog scale (VAS) and the Oswestry Disability Index (ODI) were used to measure back pain and disability. We also analyzed patients’ radiologic findings and neurological status. Perioperative and postoperative complications were recorded. Results: At the latest follow-up, the average VAS score for back pain and ODI scores had significantly improved. The radiologic assessment showed significant improvements in local kyphosis, anterior vertebral height, and the vertebral wedge angle compared with the original measures. Neurological function also improved in 18 of 20 patients. No major complications occurred perioperatively. Our techniques included preservation of the posterior ligament complex, decortication of facet joints for fusion, no tapping to increase the screw insertional torque, pre-contouring of the rods according to the “adaptive” curve obtained from postural reduction, and postoperative spinal bracing. Conclusions: Posterior short-segment decompression and fixation could be an effective surgical option for osteoporotic thoracolumbar burst fractures with neurological deficits.