Anti-Stress and Anti-ROS Effects of MnOx-Functionalized Thermosensitive Nanohydrogel Protect BMSCs for Intervertebral Disc Degeneration Repair.

Stem cell transplantation has been proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel was proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protected BMSCs from shear force and mechanical stress before and after injection but also repaired the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD. This article is protected by copyright. All rights reserved.

Percutaneous Endoscopic Robot-Assisted Transforaminal Lumbar Interbody Fusion (PE RA-TLIF) for Lumbar Spondylolisthesis: A Technical Note and Two Years Clinical Results.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and percutaneous endoscopic TLIF (PE-TILF) have been widely used in spine surgery. The use of a robot-guided technique provided several advantages; however, few studies have investigated the clinical outcomes of robot-assisted PE-TLIF (PE RA-TLIF). OBJECTIVE: The aim of this prospective cohort study was to compare the clinical outcomes of PE RA-TLIF with MIS-TLIF for the treatment of lumbar 4-5 (L4-5) spondylolisthesis. STUDY DESIGN: Prospective cohort study. SETTING: Qilu Hospital of Shandong University. METHODS: Fifty-eight cases diagnosed with L4-5 spinal stenosis with instability and Meyerding grade I spondylolisthesis (degenerative spondylolisthesis or isthmic spondylolisthesis) were included in this study. Twenty-six patients (group A) were treated with PE RA-TLIF, and the others (group B) underwent MIS-TLIF. The surgical procedures for PE RA-TLIF included the percutaneous implantation of pedicle screws (PS) under robot guidance, percutaneous fully endoscopic transforaminal decompression, and interbody fusion. The Japanese Orthopedic Association (JOA) score, the visual analog scale (VAS) for low back pain (LBP), the VAS for leg pain/numbness, and the Oswestry disability index (ODI) were used as follow-up clinical outcomes, and the lumbar interbody fusion rate was evaluated by CT. All statistical analyses were performed with SPSS 22.0, and the results were presented as mean ± standard deviation (SD). RESULTS: There were 4 cases of spinal stenosis with instability, 17 cases of degenerative spondylolisthesis, and 5 cases of isthmic spondylolisthesis in group A. For group B, there were 6 cases of spinal stenosis with instability, 19 cases of degenerative spondylolisthesis, and 7 cases of isthmic spondylolisthesis. The preoperative scores for the JOA, ODI, VAS for LBP, and VAS for leg pain were not statistically comparable between the 2 groups (P > 0.05). The incision length for decompression and interbody fusion, estimated blood loss (EBL), and 1-day and 3-day incision pain were significantly higher in group B than in group A (P < 0.05). The mean operative time was longer in group A than in group B (P < 0.05). The operation time of the first 10 cases (251 ± 24 min) was much longer than that of the last 16 cases (200 ± 17 min) in group A. The misplacement rate of percutaneous pedicle screw placement was higher in group B (P < 0.05). No infections of incisions and interbody or nerve root or dural injuries were found in either group A or B. No differences were found between the 2 groups in the JOA scores, ODI, leg pain VAS score, or lumbar interbody fusion rate at the 2-year follow-up. The VAS for back pain was better in group A than in group B (P < 0.05). LIMITATIONS: The PE RA -TLIF procedure is technically challenging and has a steep learning curve, and the study was not strictly randomized. CONCLUSION: PE RA-TLIF is a safe and effective procedure that can significantly improve the accuracy of pedicle screw placement, reduce surgical trauma, and facilitate rapid postoperative recovery. However, this technique has a steep and long learning curve and requires long-term follow-ups.

The Role of Smad2 in Transforming Growth Factor ß1-Induced Hypertrophy of Ligamentum Flavum.

BACKGROUND: Hypertrophy of the ligamentum flavum (LF) contributes to the development of spinal stenosis. Smad proteins can mediate the fibrogenesis activity through the transforming growth factor ß1 (TGF-ß1) pathway, but which Smad protein plays a more important role in the hypertrophy process of LF is unclear. METHODS: The LF samples were obtained from 50 patients. After the LF cells (LFCs) were cultured, small interfering ribonucleic acid (siRNA) that target human phosphorylated-Smad2, 3, or 4 (p-Smad2,3,4) genes was transfected into LFCs. Next, proteins from cells were extracted and the protein levels of Smad2, Smad3, and Smad4 were detected by Western blot. The messenger ribonucleic acid level of TGF-ß1 was measured by real-time polymerase chain reaction (PCR). Furthermore, an enzyme-linked immunosorbent assay was performed to test the impact of Smad2 downstream of the TGF-ß1 signaling pathway. RESULTS: Degeneration of the LF was characterized by an increase in disorganized elastic fibers and fibrotic transformation by extracellular collagen deposition. The gene expression analysis of fibrotic genes in LFCs showed that knockdown of phosphorylated-Smad2 by siRNA significantly reduced the protein expression level of TGF-ß1 compared with other groups. The enzyme-linked immunosorbent assay suggested that the protein expression level of Smad2 can influence the downstream events of TGF-ß1 signaling pathway in the LFCs. CONCLUSIONS: Our findings suggest that Smad2 plays a potential role in the pathologic development of hypertrophy of LF. We also found that Smad2 knockdown by Smad-siRNA can influence the TGF-ß1 signaling pathway through decreasing expression of TGF-ß1, tumor necrosis factor α, and nuclear factor κb.

Qishenyiqi dripping pill improves ventricular remodeling and function in patients with chronic heart failure: A pooled analysis.

BACKGROUND: Qishenyiqi dripping pill for chronic heart failure (CHF) remains controversial due to lack of high-quality trials. Therefore, we conduct this pooled-analysis to evaluate the efficacy and safety of Qishenyiqi in CHF patients. METHODS: We searched for randomized clinical trials for Qishenyiqi dripping pill in treating CHF up to August 2018 through China National Knowledge Infrastructure (CNKI), the PubMed Database, the Wanfang Database, the China Scientific Journal Database (VIP), and the Chinese Biomedicine Literature Service System. RevMan 5.3 was used for pooled analyses. Based on the New York Heart Association (NYHA) classification, the clinical therapeutic effect was collected as the primary endpoint. RESULTS: The efficacy and safety of Qishenyiqi combined with routine treatment significantly increased NYHA functional classification, left ventricular ejection fraction, cardiac index, and 6-minute walking test and decreased brain natriuretic peptide, left ventricular end-diastolic, and end-systolic dimensions with no obvious side effects in comparison with routine therapy alone. CONCLUSIONS: Together these results provide important insights into Qishenyiqi is effective and safe in improving ventricular remodeling and function of CHF patients. PROSPERO REGISTRATION NUMBER: PROSPERO106695.