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.

A comparative study of PSPVP and PSIBG in the treatment of stage II-III Kummell's disease.

BACKGROUND: Percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP) are commonly employed for Kummell's disease in stages II-III; however, these techniques produce some complications. OBJECTIVE: To compare the clinical efficacy and imaging results of percutaneous vertebroplasty + bone cement-augmented short-segment pedicle screw fixation (PSPVP) versus transpedicular intracorporeal bone grafting + pedicle screw fixation (PSIBG) in the treatment of stage II-III Kummell's disease. METHODS: A total of 69 patients admitted between November 2017 and March 2021 were included in this study; 36 of these were treated with PSPVP, and 33 were treated with PSIBG. Patients in the two groups were compared in terms of perioperative, follow-up, and imaging data. RESULTS: No statistically significant differences were found between the two groups in terms of operation duration (P > 0.05). However, the PSPVP group was superior to the PSIBG group in terms of incision length, intraoperative blood loss, and length of stay (P < 0.05). All patients were followed up for more than 12 months. The VAS score, height of anterior vertebral margin, kyphosis Cobb angle, wedge angle of the affected vertebra at seven days after surgery and last follow-up, and the ODI index at the last follow-up of the two groups were significantly improved compared with figures before surgery (P < 0.05). Compared with values before surgery, no statistically significant differences were found in the height of the posterior vertebral margin in the PSPVP group at seven days after surgery and at the last follow-up (P > 0.05). There were also no statistically significant differences in the VAS score, ODI index, kyphosis Cobb angle, and wedge angle of the affected vertebra between the two groups at corresponding time points (P > 0.05). The heights of the anterior and posterior vertebral margins in the PSIBG group were better than those in the PSPVP group after surgery and at the last follow-up (P < 0.05). In the PSPVP group, a pedicle screw fracture occurred in one patient two months after surgery, while an upper adjacent vertebral fracture occurred in one patient eight months after surgery. CONCLUSION: Both PSPVP and PSIBG can achieve good early clinical efficacy in the treatment of stage II-III Kummell's disease, with PSPVP being relatively less invasive while producing a poorer orthopedic effect and more complications than PSIBG.

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.

An assessment of morphological and pathological changes in paravertebral muscle degeneration using imaging and histological analysis: a cross-sectional study.

BACKGROUND: The high signal of paravertebral muscle (PVM) on T2-weighted image (T2WI) is usually considered to be fatty degeneration. However, it is difficult to distinguish inflammatory edema from fatty degeneration on T2WI. The purpose of this study was to identify different types of PVM high signal in patients with low back pain (LBP) through magnetic resonance imaging (MRI) and histology. METHODS: Seventy patients with LBP underwent MRI. The signal change of multifidus both on T2WI and fat suppression image (FSI) was quantified by Image J. Furthermore, 25 of the 70 patients underwent surgery for degenerative lumbar disease and their multifidus were obtained during the operation. Histological analysis of the samples was performed by HE staining. RESULT: Three types of PVM signal changes were identified from the MRI. Type 1 (n = 36) indicated fatty degeneration characterized by a high signal on T2WI and low signal on FSI. High signal on both T2WI and FSI, signifying type 2 meant inflammatory edema (n = 9). Type 3 (n = 25) showed high signal on T2WI and partial signal suppression on FSI, which meant a combination of fatty degeneration and inflammatory edema. Histological results were consistent with MRI. Among the 25 patients who underwent surgery, type 1 (n = 14) showed adipocytes infiltration, type 2 (n = 3) showed inflammatory cells infiltration and type 3 (n = 8) showed adipocytes and inflammatory cells infiltration. CONCLUSION: From our results, there are three types of pathological changes in patients with PVM degeneration, which may help to decide on targeted treatments for LBP.

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.

Tophaceous gout causing lumbar stenosis: A case report.

RATIONALE: Gout in the spine is very rare. The clinical symptoms of the spinal gout are various and lack of specificity. The authors report a case of spinal gout causing lumbar stenosis. We never find such wide-invasive spinal gouty lesion in the published studies. PATIENT CONCERNS: A 68-year-old male had low back pain radiating to bilateral lower limbs, accompanying with intermittent claudication that lasted for 3 months and aggravated 5 days ago. DIAGNOSES: Spinal gout, lumbar stenosis. INTERVENTIONS: The patient underwent L2-L4 laminectomy, L2/3 L3/4 an d L4/5 discectomy and transforaminal lumbar interbody fusion with pedicle screw fixation. OUTCOMES: Dual-energy computed tomography detected extensive tophaceous deposits in L1/2 L2/3 L3/4 and L4/5 lumbar discs as well as the posterior column, especially L2-L3 and L4-L5 facet joints. During the surgery, we found a mass of chalky white material at the posterior column of L3 to L5 vertebral bodies, which also involved the intervertebral discs. Pathological examination confirmed the diagnosis of spinal gout. LESSONS: Although spinal gout is thought to be rare, the diagnosis should be considered if the patient had severe back pain and a history of gout. Dual-energy computed tomography is highly recommended for these patients.

Pelvic reconstruction with different rod-screw systems following Enneking type I/I + IV resection: a clinical study.

The mechanical outcomes of patients with pelvic bone tumors involving zone I or zone I + IV who received resection and different reconstructions are not clear. Therefore, the purpose of this study was to compare the outcomes of different rod-screw systems in reconstruction for these patients, and evaluate the relative risk of mechanical failure for them. We reviewed 30 patients for a mean duration of 40.4 months of follow-up (range, 13.1-162.2 months), five patients had mechanical complications. The mechanical survival rate of two-rod and four-screw (TRFS) group was significantly higher than one-rod and two-screw (ORTS) group (p = 0.000). The implant survival rate was correlated with ages (p = 0.010), younger people are more likely to fail. Thus, TRFS fixation for pelvic reconstruction after Enneking type I/I + IV resection can provide better short to long-term mechanical stability compared with ORTS fixation, the strength of ORTS fixation is not enough. In addition, biological reconstruction such as autologous bone graft is recommended for the patients who are younger or suffered from benign tumor. As for the patients who are older, with malignant tumors, underwent adjuvant radiotherapy or chemotherapy, functional reconstruction with bone cement is a good choice.

Minimally invasive plate osteosynthesis vs conventional fixation techniques for surgically treated humeral shaft fractures: a meta-analysis.

BACKGROUND: In this study, we performed a meta-analysis to identify whether minimally invasive plate osteosynthesis (MIPO) was superior to conventional fixation techniques (CFT) for treating humeral shaft fractures. METHODS: A systematic literature search was conducted up to February 2016 in ScienceDirect, Springer, MEDLINE, and PubMed databases for relevant papers that compared the outcomes of MIPO with CFT, such as open reduction with plate osteosynthesis (ORPO) and intramedullary nail (IMN) for treating humeral shaft fractures. Meta-analysis was performed with Review Manager 5.0 software. RESULTS: According to the search strategy, eight studies that covered 391 patients were enrolled, including four randomized controlled trials (RCTs), two prospective cohort trials, and two retrospective cohort trials. Our meta-analysis did not detect any significant difference between MIPO and CFT (IMN and ORPO) in terms of operative time, fracture union rate, and fracture union time. However, MIPO has a less rate of complications and iatrogenic radial nerve palsy than that of ORPO and higher adjacent joint function scores than those of IMN (p < 0.05). CONCLUSIONS: Based on the present evidence, this meta-analysis suggested that MIPO was a better choice for treating humeral shaft fractures than CFT. However, more high-quality randomized trials are still needed to further confirm this conclusion in the future.