Astaxanthin reduces inflammation and promotes a chondrogenic phenotype by upregulating SIRT1 in osteoarthritis.

OBJECTIVE: To investigate the effects of astaxanthin (AST) on mouse osteoarthritis (OA) and lipopolysaccharide (LPS)-induced ATDC5 cell damage and to explore whether SIRT1 protein plays a role. METHODS: In this study, some mouse OA models were constructed by anterior cruciate ligament transection (ACLT). Imaging, molecular biology and histopathology methods were used to study the effect of AST administration on traumatic OA in mice. In addition, LPS was used to stimulate ATDC5 cells to mimic the inflammatory response of OA. The effects of AST on the cell activity, inflammatory cytokines, matrix metalloproteinases and collagen type II levels were studied by CCK8 activity assay, reverse transcription polymerase chain reaction and protein imprinting. The role of SIRT1 protein was also detected. RESULTS: In the mouse OA model, the articular surface collapsed, the articular cartilage thickness and cartilage matrix protein abundance were significantly decreased, while the expression of inflammatory cytokines and matrix metalloproteinases was increased; but AST treatment reversed these effects. Meanwhile, AST pretreatment could partially reverse LPS-induced ATDC5 cell damage and upregulate SIRT1 expression, but this protective effect of AST was attenuated by concurrent administration of the SIRT1 inhibitor Ex527. CONCLUSION: AST can protect against the early stages of OA by affecting SIRT1 signalling, suggesting that AST might be a potential therapeutic agent for OA treatment.

Application of Kirschner wire placement guided technology in paediatric supracondylar humerus fractures.

BACKGROUND: To analyze the clinical efficacy of K-wire placement guided technology in paediatric supracondylar humerus fractures. METHODS: A retrospective study was conducted in 105 patients who underwent closed reduction and percutaneous pinning surgeries in our hospital from June 2019 to August 2022. 54 patients treated with a assisted reduction fixation device to assist in closed reduction and percutaneous K-wire cross-fixation were allocated into the Non-guided group, and 51 patients with K-wire placement guided technology to guide K-wire placement were assigned into the Guided group. The operation duration, number of disposable K-wire placement, intraoperative fluoroscopy frequency, Baumann angle, carrying angle, fracture healing time and Flynn score of elbow joint function at the final follow-up were compared between two groups. The postoperative complications of two groups were recorded. RESULTS: There were significant differences between two groups in terms of operation duration, intraoperative fluoroscopy frequency, and disposable K-wire placement rate (p < 0. 05), while no significant differences of Baumann angle, carrying angle and the fracture healing time between two groups were observed (p > 0. 05). In the control group, ulnar nerve injury in 2 case, pin site infection in 4 cases, mild cubitus varus in 2 cases and loss of reduction in 4 cases were detected. In the study group, ulnar nerve injury in 1 case, pin site infection in 2 cases and loss of reduction in 1 case was observed. There was no significant difference in Flynn scores between two groups. CONCLUSION: K-wire placement guided technology is simple and convenient. The application of K-wire placement guided technology could relatively improved disposable K-wire placement rate, shorten the intraoperative fluoroscopy frequencies and reduce complication rates.

Endo-TLIF versus MIS-TLIF in 1-segment lumbar spondylolisthesis: A prospective randomized pilot study.

OBJECTIVE: To evaluate the curative efficacy by comparing perioperative characteristics and 1.5-year observational outcomes in 1-segment lumbar spondylolisthesis between traditional minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and optimized Endoscopic TLIF techniques. METHODS: The study was a single-center, randomized controlled trial comparing two different treatment approaches for 1-segment lumbar spondylolisthesis. 102 patients treated by MIS-TLIF (48 cases) or Endo-TLIF (54 cases) were included from March 2018 to April 2019. Perioperative parameters and clinical outcomes were evaluated. Degree of slip were measured, and fusion rates were determined at 18 months after surgery. RESULTS: The Endo-TLIF group had similar return to work time and rate. Blood loss, left bed time, analgesic ratio were significantly less in Endo-TLIF group. The Endo-TLIF group had a significantly longer operative time. Significant postoperative reduction in %slip was showed in both groups. The VAS and ODI improved significantly in both groups after surgery. Significant decreases in low-back pain in Endo-TLIF group were found at postoperative day 1 and 3 months. The fusion rate in the two groups was similar. CONCLUSION: Endo-TLIF surgery with a C-shaped working tube and a visualization system may be regarded as an efficient alternative surgery for 1-segment lumbar spondylolisthesis. It is a safe and minimally invasive way to perform this surgery and has shown satisfactory clinical outcomes. TRIAL REGISTRATION: ChiCTR1800015197, 13 March 2018. TRIAL REGISTRY: Chinese Clinical Trial Registry. Registered 13 March 2018. http://www.chictr.org.cn/showproj.aspx?proj=25865.

Deletion of p16 accelerates fracture healing in geriatric mice.

The biomarker p16 plays a role in aging and is upregulated in aged organs and cells, including bone marrow mesenchymal stem cells (BM-MSCs), which play a leading role in fracture healing. Several studies have reported delayed fracture healing in geriatric mice. However, the relationship between p16 expression and fracture healing in geriatric mice remains poorly understood. In this study, we found that fracture healing was accelerated in p16 deletion (p16-/-) mice, and the number of migrated BM-MSCs from p16-/- mice increased. The expressions of SDF-1 and CXCR4 were also upregulated in p16-/- mice. Increased cell percentage at S phase in cell cycle, enhanced expressions of CDK4/6, pRB, and E2F1, decreased expression of RB, and elevated expressions of SOX9, PCNA, and COL2A1 were detected in p16-/- mice. The expressions of COL10A1, MMP13, OSTERIX, and COL1A1 were also high in p16-/- mice. Moreover, the expressions of p-AKT, p-mTOR, HIF-1α, and VEGF-A in BM-MSCs and expression of VEGF-A in callus were upregulated in p16-/- mice. The expression of VEGF in the serum of p16-/- mice was also higher than that of wild type mice. Thus, deletion of p16 enhances migration, division, and differentiation of BM-MSCs, promotes proliferation and maturation of chondrocytes, activates osteoblastogenesis, and facilitates vascularization to accelerate fracture healing, providing a novel strategy to treat fracture in the elderly.

[Short-term effectiveness of percutaneous pedicle screw fixation combined with intravertebral allograft by different methods for thoracolumbar fractures].

OBJECTIVE: To investigate the short-term effectiveness of percutaneous pedicle fixation combined with intravertebral allograft by different methods for thoracolumbar fractures. METHODS: The clinical data of 94 patients with single segment thoracolumbar fracture who underwent percutaneous pedicle fixation combined with intravertebral allograft by different methods between October 2018 and October 2019 were retrospectively analyzed. According to the different methods of intravertebral allograft, they were divided into group A (bone grafting by Jack dilator, 40 cases) and group B (bone grafting by funnel, 54 cases). There was no significant difference between the two groups ( P>0.05) in the gender, age, body mass index, cause of injury, injured segment, Wolter index, time from injury to operation, and preoperative visual analogue scale (VAS) score, injured vertebral height ratio, and Cobb angle. The operation time, fluoroscopy frequency, allograft volume, and complications were recorded and compared between the two groups. VAS score of low back pain was used to evaluate the remission of clinical symptoms before operation, at 3 days, 3 months, 12 months after operation, and at last follow-up. The injured vertebral height ratio and Cobb angle were measured before operation, at 3 days, 3 months, and 12 months after operation. RESULTS: The operation time, fluoroscopy frequency, and allograft volume in group A were significantly higher than those in group B ( P<0.05). No complication occurred after operation, such as loosening or fracture of internal fixation. And bone grafting in the injured vertebrae healed at last follow-up. The VAS score, injured vertebral height ratio, and Cobb angle at each postoperative time point significantly improved when compared with preoperative ones ( P<0.05); compared with 3 days postoperatively, the VAS score improved further after 3 months, but the injured vertebral height ratio decreased and the Cobb angle increased, and the differences were significant ( P<0.05). There was no significant difference in the VAS scores of low back pain between the two groups at each time point after operation ( P>0.05); the injured vertebrae height ratio in group A was significantly higher than that in group B, and the Cobb angle was significantly lower than that in group B, all showing significant differences ( P<0.05). CONCLUSION: The intravertebral allograft via Jack dilator can restore the height and decrease the Cobb angle of the injured vertebrae, but accompanied with higher fluoroscopy frequency and longer operation time when compared with funnel bone grafting. For patients with single level thoracolumbar fractures, intravertebral allograft via Jack dilator is recommended.

[Comparison of two methods for preparing knee osteochondral injury models in mice].

OBJECTIVE: To observe the effect of using tungsten drills to prepare mouse knee osteochondral injury model by comparing with the needle modeling method, in order to provide an appropriate animal modeling method for osteochondral injury research. METHODS: A total of 75 two-month-old male C57BL/6 mice were randomly divided into 3 groups ( n=25). Mice in groups A and B were used to prepare the right knee osteochondral injury models by using needles and tungsten drills, respectively; group C was sham-operation group. The general condition of the mice was observed after operation. The samples were taken at 1 day and 1, 2, 4, and 8 weeks after modeling, and HE staining was performed. The depth, width, and cross-sectional area of the injury site at 1 day in groups A and B were measured, and the percentage of the injury depth to the thickness of the articular cartilage (depth/thickness) was calculated. Toluidine blue staining and immunohistochemical staining for collagen type Ⅱ were performed at 8 weeks, and the International Cartilage Research Society (ICRS) score was used to evaluate the osteochondral healing in groups A and B. RESULTS: All mice survived to the completion of the experiment. HE staining showed that group C had normal cartilage morphology. At 1 day after modeling, the injury in group A only broke through the cartilage layer and reached the subchondral bone without entering the bone marrow cavity; the injury in group B reached the bone marrow cavity. The depth, width, cross-sectional area, and depth/thickness of the injury in group A were significantly lower than those in group B ( P<0.05). At 1, 2, 4, and 8 weeks after modeling, there was no obvious tissue filling in the injured part of group A, and no toluidine blue staining and expression of collagen type Ⅱ were observed at 8 weeks; while the injured part of group B was gradually filled with tissue, the toluidine blue staining and the expression of collagen type Ⅱ were seen at 8 weeks. At 8 weeks, the ICRS score of group A was 8.2±1.3, which was lower than that of group B (13.6±0.9), showing significant difference ( t=-7.637, P=0.000). CONCLUSION: The tungsten drills can break through the subchondral bone layer and enter the bone marrow cavity, and the injury can heal spontaneously. Compared with the needle modeling method, it is a better method for modeling knee osteochondral injury in mice.

GIT1 protects traumatically injured spinal cord by prompting microvascular endothelial cells to clear myelin debris.

The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). As phagocytes do, microvascular endothelial cells (MECs) participate in myelin debris clearance at the injury site within one week. Our group has verified that G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) is essential in autophagy and angiogenesis, both of which are tightly related to the uptake and degradation of myelin debris by MECs. Here, we analyzed the performance and mechanism of GIT1 in myelin debris clearance after SCI. The SCI contusion model was established and in vitro MECs were treated with myelin debris. Better recovery from traumatic SCI was observed in the GIT1 WT mice than in the GIT1 KO mice. More importantly, we found that GIT1 prompted MECs to clear myelin debris and further enhanced MECs angiogenesis in vivo and in vitro. Mechanistically, GIT1-mediated autophagy contributed to the clearance of myelin debris by MECs. In this study, we demonstrated that GIT1 may prompt MECs to clear myelin debris via autophagy and further stimulate MECs angiogenesis via upregulating VEGF. Our results indicate that GITI may serve as a promising target for accelerating myelin debris clearance and improving SCI recovery.

Spontaneous Cervical Intradural Disc Herniation Presenting withBrown-Sequard Syndrome at C6-C7 level.

INTRODUCTION: Intradural disc herniation is a rare disease and it accounts for 0.26-0.30% of all herniated discs. Little was known about intradural disc herniation in the previous studies. CASE REPORT: Here, we report a 49-year-old male patient with Brown-Sequard syndrome caused by spontaneous cervical intradural disc herniation at C6-C7 level. CONCLUSIONS: It is difficult to be diagnosed before the surgery through computed tomography scans, myelograms, and magnetic resonance image scans. Once it was diagnosed, an operation should be performed.

Self-management interventions for cancer survivors: A systematic review and evaluation of intervention content and theories.

OBJECTIVE: Self-management has been proposed as a strategy to help cancer patients optimize their health and well-being during survivorship. Previous reviews have shown variable effects of self-management on outcomes. The theoretical basis and psychoeducational components of these interventions have not been evaluated in detail. We aimed to evaluate the evidence for self-management and provide a description of the components of these interventions. METHODS: We conducted a systematic review of self-management interventions for adults who had completed primary cancer treatment by searching MEDLINE, EMBASE, PsychINFO, CINAHL, Scopus, Cochrane Database of Systematic Reviews, National Institutes of Health Clinical Trials Registry, and Cochrane CENTRAL Registry of Controlled Trials. We included experimental and quasiexperimental designs. Data synthesis included narrative and tabular summary of results; heterogeneity of interventions and outcomes precluded meta-analysis. Study quality was evaluated using the Cochrane risk of bias tool or the risk of bias of nonrandomized studies tool. RESULTS: Forty-one studies published between 1994 and 29 March 2018 were included. Studies were predominantly randomized controlled trials and targeted to breast cancer survivors. A variety of intervention designs, psychoeducational components, and outcomes were identified. Less than 50% of the studies included a theoretical framework. There was variability of effects across most outcomes. Risk of bias could not be fully assessed. CONCLUSIONS: There are limitations in the design and research on self-management interventions for cancer survivors that hinder their translation into clinical practice. Further research is needed to understand if these interventions are an important type of support for cancer survivors.

Edaravone inhibits autophagy after neuronal oxygen-glucose deprivation/recovery injury.

PURPOSE OF THE STUDY: Edaravone is an oxygen free radical scavenger that is widely used to treat ischemic injury to the nervous system. This study investigated the effect of edaravone pretreatment on neurons subjected to oxygen-glucose deprivation/recovery (OGD/R) injury. MATERIALS AND METHODS: Common neurons were subjected to oxygen and glucose deprivation for 1 h, followed by oxygen and glucose recovery for 0.5, 2, 6 and 12 h to establish the OGD/R model. Autophagy was assessed by electron microscope observation of autophagosomes, cell immunofluorescence, mRFP-GFP-LC3 virus cell fluorescence and western blotting analyses of the autophagy-related proteins. The findings showed that at OGD/R 2 h autophagy was high. Next, neurons were pretreated with different concentrations of edaravone (0, 5, 10, 25, 50 and 100 µM) before establishing the OGD/R model. Western blotting was used to analyze the expression of autophagy-related proteins. The CCK-8 assay was used to analyze cell viability after pretreatment with different concentrations of edaravone. Optimal inhibition of autophagy was achieved with the concentration of edaravone 50 µM. Neurons pretreated with 50 µM edaravone and established OGD/R model were analyzed for autophagy levels. RESULTS: At every OGD/R time point autophagy was lower in neurons pretreated with edaravone than in those not pretreated with the drug. The difference was statistically significant without OGD/R 12 h. CONCLUSIONS: Pretreatment with edaravone may reduce the level of autophagy in neurons subjected to OGD/R injury.

Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate-Induced Excitotoxicity.

New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (≈7.2 µm in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl-2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases.

Effect of zoledronic acid on lumbar spinal fusion in osteoporotic patients.

PURPOSE: To investigate the effect of zoledronic acid (ZA) on lumbar spinal fusion in patients with osteoporosis. METHODS: This retrospective study includes 94 osteoporotic patients suffering from lumbar degenerative diseases or lumbar fracture who underwent lumbar spinal fusion in our institution from January 2013 to August 2014. They were divided into ZA group and control group according to whether the patient received ZA infusion or not. The patients in ZA group were given 5 mg intravenous ZA at the 3rd-5th days after operation. All patients took daily oral supplement of 600 mg calcium carbonate and 800 IU vitamin D during the follow-up after operation. The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Short Form 36 (SF-36) scores were recorded preoperatively and post-operatively to evaluate the clinic outcomes; the spinal fusion was assessed by X-ray or CT Scan. RESULTS: 64 patients finished the final follow-up, including 30 patients in ZA group and 34 patients in control group. No significant difference was observed in gender, age, and preoperative BMI VAS, ODI, and SF-36 scores between the two groups (P > 0.05). The post-operative VAS and ODI scores decreased rapidly at 3 and 6 months, but rose back slightly at 12 and 24 months in both groups. On the contrary, post-operative SF-36 scores increased rapidly at 3 and 6 months, while fell back slightly at 12 and 24 months, with a statistically significant difference between the two groups at 12 months, but not at 3 and 6 month post-operation. The spinal fusion rate in ZA group was 90% at 6 months, 92% at 12 months, while it was 75% at 6 months, 92.86% at 12 months in control group, significantly different between the two groups at 12 months, but not at 6 months. In the whole follow-up period, adjacent vertebral compressing fracture occurred in five patients in control group, none in ZA group. No pedicle screw loosening was observed in ZA group, with six in control group. CONCLUSIONS: Zoledronic acid accelerates spinal fusion, shortens the time of fusion without changing fusion rate, and also decreases the risk of adjacent vertebral compressing fracture and the rate of pedicle screw loosening, resulting in the improvement of clinical outcomes and quality of life.