4-Octyl itaconate protects chondrocytes against IL-1ß-induced oxidative stress and ferroptosis by inhibiting GPX4 methylation in osteoarthritis.

The role of oxidative stress and ferroptosis in osteoarthritis (OA) pathogenesis is increasingly recognized. Notably, 4-octyl Itaconate (OI) has been documented to counteract oxidative stress and inflammatory responses, highlighting its therapeutic potential in OA. This study explored the effects of OI on GPX4 methylation, oxidative stress, and ferroptosis in chondrocytes affected by OA. Our results demonstrated that OI mitigated IL-1ß-induced chondrocyte degeneration in a dose-dependent manner. It also suppressed reactive oxygen species (ROS) production and sustained GPX4 expression, thereby attenuating the degenerative impact of IL-1ß and Erastin on chondrocytes by curtailing ferroptosis. Moreover, we observed that blocking GPX4 methylation could alleviate IL-1ß-induced degeneration, oxidative stress, and ferroptosis in chondrocytes. The regulatory mechanism of OI on GPX4 expression in chondrocytes involved the inhibition of GPX4 methylation. In a mouse model of OA, OI's protective effects against OA were comparable to those of Ferrostatin-1. Thus, OI reduced chondrocyte degeneration, oxidative stress, and ferroptosis by inhibiting GPX4 methylation, offering a novel mechanistic insight into its therapeutic application in OA.

"Early Efficacy and Safety of Unilateral Biportal Endoscopic Lumbar Interbody Fusion Versus Minimal Invasive in the Treatment of Lumbar Degenerative Diseases".

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To compare the early clinical efficacy and radiologic outcomes between unilateral biportal endoscopic lumbar interbody fusion (ULIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). SUMMARY OF BACKGROUND DATA: Along with the continuous development of endoscopic technology, the early safety and effectiveness of ULIF technology are still unknown. MATERIALS AND METHODS: This retrospective study included 61 patients who underwent fusion surgery through ULIF or MIS-TLIF in 2021. Twenty-nine patients underwent ULIF (group A), and 32 underwent MIS-TLIF (group B). Fusion rate, bone graft volume, hidden blood loss (HBL), C-reactive protein level, operative time, Oswestry Disability Index , Visual Analog Scale score, and MacNab criteria were assessed in both groups. RESULTS: The Visual Analog Scale score for back pain in the early postoperative period was significantly lower in group A than in group B ( P <0.05). All other clinical scores showed improvement, with no significant difference between the 2 groups ( P >0.05). There was no statistically significant difference in postoperative C-reactive protein levels and fusion rates between the 2 groups ( P >0.05). However, HBL was higher and operative time was longer in group A than in group B ( P <0.05). Most importantly, there were no statistically significant differences between groups A and B in fusion rate, length of stay and bone graft volume ( P >0.05). No serious surgical complications occurred in our study. CONCLUSIONS: ULIF is a new option for lumbar fusion. Despite the drawbacks of longer operation time and higher HBL, ULIF may be a viable alternative to MIS-TLIF as technology advances.

[Treatment of stage â ¡-â ¢ Kümmell disease with robot-assisted bone cement-augmented pedicle screw fixation].

OBJECTIVE: To evaluate the early clinical efficacy of robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation in the treatment of stageⅡ-Ⅲ Kümmell disease. METHODS: The clinical data of 20 patients with stageⅡ-Ⅲ Kümmell's disease who underwent robot-assisted percutaneous bone cement-augmented pedicle screw fixation between June 2017 and January 2021 were retrospectively analyzed. There were 4 males and 16 females, aged from 60 to 81 years old with an average age of (69.1±8.3) years. There were 9 cases of stageⅡand 11 cases of stage Ⅲ, all of which were single vertebral lesions, including 3 cases of T11, 5 cases of T12, 8 cases of L1, 3 cases of L2, and 1 case of L3. These patients did not exhibit symptoms of spinal cord injury. The operation time, intraoperative blood loss, and complications were recorded. The position of pedicle screws and the filling and leakage of bone cement in gaps were observed using postoperative CT 2D reconstruction. The data of the visual analogue scale (VAS), Oswestry disability index (ODI), kyphosis Cobb angle, wedge angle of the diseased vertebra, and anterior and posterior vertebral height on lateral radiographs were statistically analyzed preoperatively, 1 week postoperatively, and at the final follow-up. RESULTS: Twenty patients were followed up for 10 to 26 months, with an average follow-up of (16.0±5.1) months. All operations were successfully completed. The surgical duration ranged from 98 to 160 minutes, with an average of (122±24) minutes. The intraoperative blood loss ranged from 25 to 95 ml, with an average of (45±20) ml. There were no intraoperative vascular nerve injuries. A total of 120 screws were inserted in this group, including 111 screws at grade A and 9 screws at grade B according to the Gertzbein and Robbins scales. Postoperative CT indicated that the bone cement was well-filled in the diseased vertebra, and cement leakage occurred in 4 cases. Preoperative VAS and ODI were (6.05±0.18) points and (71.10±5.37)%, respectively, (2.05±0.14) points and (18.57±2.77)% at 1 week after operation, and (1.35±0.11) points and (15.71±2.12) % at final follow-up. There were significant differences between postoperative 1 week and preoperative, and between final follow-up and postoperative 1 week(P<0.01). Anterior and posterior vertebral height, kyphosis Cobb angle, and wedge angle of the diseased vertebra were(45.07±1.06)%, (82.02±2.11)%, (19.49±0.77) °, and (17.56±0.94) ° preoperatively, respectively, (77.00±0.99)%, (83.04±2.02)%, (7.34±0.56) °, and (6.15±0.52) ° at 1 week postoperatively, and (75.13±0.86)%, (82.39±0.45)%, (8.38±0.63) °, and (7.09±0.59) ° at the final follow-up. CONCLUSION: Robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation demonstrates satisfactory short-term efficacy in treating stageⅡ-Ⅲ Kümmell's disease as an effective minimally invasive alternative. However, longer operation times and strict patient selection criteria are necessary, and long-term follow-up is required to determine its lasting effectiveness.

A comparative study of robot-assisted and traditional surgeries in the treatment of thoracolumbar fractures based on 1-year follow-up observation.

BACKGROUND: There are conflicting results for robot-assisted (RA) pedicle screw fixation compared with freehand (FH) pedicle screw fixation. OBJECTIVE: This study was designed to retrospectively compare the accuracy and efficacy of RA percutaneous pedicle screw fixation and traditional freehand FH pedicle screw fixation in the treatment of thoracolumbar fractures. METHODS: A total of 26 cases were assigned to the RA group, and 24 cases were assigned to the FH group. The operation time, bleeding volume, and visual analog scale (VAS) score 1 day after the operation, and the anterior/posterior (A/P) vertebral height ratio of the injured vertebrae at 3 days and at internal fixation removal 1 year after the operation were compared between the two groups. Pedicle screw position accuracy was assessed according to Gertzbein criteria. RESULTS: The operation times of the RA group and FH group were 138.69 ± 32.67 minutes and 103.67 ± 14.53 minutes, respectively, and the difference was statistically significant. The intraoperative blood loss was 49.23 ± 22.56 ml in the RA group and 78.33 ± 23.90 ml in the FH group, and the difference was statistically significant. There was a significant difference in the A/P vertebral height ratio of the injured vertebrae 3 days after the operation compared with before the operation in both groups (P < 0.05). There was a significant difference in the A/P vertebral height ratio of the injured vertebrae 3 days after the operation compared with that at fixation removal in both groups (P < 0.05). CONCLUSION: The application of RA orthopedic treatment for thoracolumbar fractures can achieve good fracture reduction.

Intracellular Delivery of Itaconate by Metal-Organic Framework-Anchored Hydrogel Microspheres for Osteoarthritis Therapy.

Treatment of osteoarthritis (OA) remains a significant clinical challenge. Itaconate (IA), an emerging regulator of intracellular inflammation and oxidative stress, may potentially be harnessed to treat OA. However, the short joint residence time, inefficient drug delivery, and cell-impermeable property of IA can seriously hamper the clinical translation. Herein, IA-encapsulated zeolitic imidazolate framework-8 (IA-ZIF-8) nanoparticles were self-assembled by zinc ions, 2-methylimidazole, and IA to render them pH-responsive. Subsequently, IA-ZIF-8 nanoparticles were firmly immobilized in hydrogel microspheres via one-step microfluidic technology. It was demonstrated in vitro experiments that IA-ZIF-8-loaded hydrogel microspheres (IA-ZIF-8@HMs) exhibited good anti-inflammatory and anti-oxidative stress effects by releasing pH-responsive nanoparticles into chondrocytes. Importantly, compared with IA-ZIF-8, IA-ZIF-8@HMs showed better performance in the treatment of OA due to their superior performance in sustained release. Thus, such hydrogel microspheres not only hold enormous potential for OA therapy, but also provide a novel avenue for cell-impermeable drugs by constructing appropriate drug delivery systems.

Four-octyl itaconate improves osteoarthritis by enhancing autophagy in chondrocytes via PI3K/AKT/mTOR signalling pathway inhibition.

Osteoarthritis (OA) is a highly prevalent and chronic disorder that is associated with a substantial social and economic burden. Itaconate, as an important regulator of cellular inflammation, is a metabolite synthesised by an enzyme encoded by immune-responsive gene 1. However, there are few studys regarding the effects of itaconate on OA. Here, we show the effect of the cell-permeable itaconate derivative 4-octyl itaconate (OI) on OA. OI attenuates the chondrocyte apoptosis induced by interleukin 1ß (IL-1ß) in vitro, indicating that OI protect chondrocytes against apoptosis. Moreover, OI ameliorates the chondrocyte autophagy inhibition induced by IL-1ß via the inhibition of PI3K/AKT/mTOR signalling pathway. Finally, OI enhances autophagy and reduces cartilage degradation in a rat model of OA established by destabilization of medial meniscus (DMM). In summary, our findings reveal that OI is involved in regulating the progression of OA. The above results shed light on the treatment of OA.

Percutaneous Transforaminal Endoscopic Decompression for Lumbar Lateral Recess Stenosis.

Objective: The aim of this study was to evaluate the treatment efficacy of lateral spinal stenosis through the decompression of the nerve root under a multiple planar endoscope. Methods: From January 2017 to March 2019, 52 patients with lumbar spinal stenosis or lumbar spinal stenosis combined with intervertebral disc herniation had been treated via transforaminal approach spinal endoscopy. Our study retrospectively analyzed the treatment outcome. All patients experienced complications with different degrees of facet joint hyperplasia and ligamentum flavum hyperplasia and hypertrophy. Some patients suffered disc herniation. All patients were treated with percutaneous transforaminal approach multiple planar endoscopic decompression. The visual analog scale (VAS) and the Oswestry Disability Index (ODI) were compared before and after the operation, as were the horizontal foramen areas of the medial margins of the upper and lower pedicles of the vertebral arch. The treatment effectiveness was evaluated. Results: VAS and ODI scores were significantly improved at postoperative 3 days, 3 months, 6 months, and the last follow-up (P < 0.05). The area of the intervertebral foramen was 422.5 ± 159.2 mm2 preoperatively and 890.8 ± 367.7 mm2 postoperatively, the difference was statistically significant (P < 0.05). Conclusion: Percutaneous transforaminal approach multiple planar endoscopic decompression could achieve an accurate and effective decompression of the lumbar lateral spinal canal. This procedure has good short-term effects, and is especially suitable for elderly patients.

Activation of AKT signaling via small molecule natural compound prevents against osteoblast apoptosis and osteonecrosis of the femoral head.

Vinpocetine (Vinp), a natural compound extracted from the leaves of Phyllostachys pubescens with apoptosis modulatory properties in variety of disorders. In the present study, we investigated the possible mechanism of Vinp in alleviating of the progress of osteonecrosis of the femoral head (ONFH) both in vitro and in vivo experiments. The results showed that treatment with Vinp suppressed the dexamethasone (Dex) induced over-regulation of ROS level and apoptotic factors. Mechanistically, the Vinp activated Akt signaling pathway in osteoblast. Moreover, Vinp exerted a protective role in animal ONFH model. To summarize, this work illustrated Vinp possessed a new potential therapeutic drug in ONFH.

Comparing Augmentative Plating and Exchange Nailing for the Treatment of Nonunion of Femoral Shaft Fracture after Intramedullary Nailing: A Meta-analysis.

OBJECTIVE: The aim of this meta-analysis was to systematically evaluate the efficacy of augmentative plating (AP) and exchange nailing (EN) in the treatment of nonunion of femoral shaft fracture. METHODS: For the present meta-analysis, PubMed, EMBASE, and the Cochrane Library were searched to identify relevant articles up to April 2019. Two investigators independently evaluated the quality of original publications following the guidelines proposed by the Cochrane Handbook. Data were extracted from the studies and analyzed using Review Manager 5.3. RESULTS: Five studies were included in this meta-analysis, with a total of 506 patients. There were 232 patients in the AP group and 276 patients in the EN group. The AP group was associated with higher union rate (OR, 11.66; 95% CI, 4.31-31.50; P < 0.01), shorter union time (SMD, -1.10; 95% CI, -2.09 to -0.11; P = 0.03), shorter operation time (SMD, -0.55; 95% CI, -0.88 to -0.21; P < 0.01), less blood loss (SMD, -1.72; 95% CI, -3.33 to -0.11; P < 0.01), and fewer complications (OR, -0.11; 95% CI, -0.16 to -0.07; P < 0.01) than the EN group. CONCLUSION: The results of the meta-analysis showed that AP is found to be superior for nonunion of femoral shaft fractures in both intraoperatively (ie, shorter operation time and less blood loss) and postoperatively (ie, higher union rate, shorter union time, and lower complication rate). Overall, AP was superior to EN in the treatment of nonunion of femoral shaft fractures after intramedullary nailing (IMN).