Safety of Traditional Growing Rods in Patients with Early-Onset Congenital Scoliosis Associated with Type-I Split Cord Malformation.

BACKGROUND: Literature regarding the application of traditional growing rod (TGR) instrumentation in patients with early-onset congenital scoliosis with type-I split cord malformation is scarce. The purpose of the present study was to assess the safety and effectiveness of TGR surgery and repeated lengthening procedures in patients with congenital scoliosis with type-I split cord malformation not treated with prophylactic osseous spur excision. METHODS: Thirteen patients with early-onset congenital scoliosis associated with type-I split cord malformation and a stable neurologic status between March 2009 and July 2020 were recruited. All patients underwent primary TGR surgery and subsequent repeated lengthening procedures without osseous spur excision by the same surgical team. Clinical information and radiographic data from the preoperative, postoperative, and latest follow-up periods were collected. RESULTS: The mean preoperative Cobb angle of the major coronal curve was 74.62° ± 25.59°, the mean early postoperative angle was 40.23° ± 17.89°, and the mean latest follow-up angle was 40.62° ± 16.60°. The scoliotic deformity correction percentage was 46.81% ± 12.26% after the initial operation and 45.08% ± 15.53% at the latest follow-up. Compared with the preoperative values, significant improvements were observed in the coronal and sagittal balance early postoperatively and at the latest follow-up (p < 0.05 for all). The average annual amounts of spinal height gained were 15.73 ± 5.95 mm at T1-S1, 8.94 ± 3.94 mm at T1-T12, and 12.02 ± 6.70 mm between the instrumented segments. The total height gained at T1-S1 and T1-T12 was 72.18 ± 28.74 mm and 37.62 ± 12.53 mm, respectively. No intraoperative neurophysiological monitoring events were observed, and no case of neurological deficit was observed postoperatively or during follow-up. CONCLUSIONS: Patients without neurologic deficit and having a stable neurologic exam who have early-onset congenital scoliosis associated with type-I split cord malformation can safely and effectively undergo TGR surgery, followed by repeated lengthening procedures, without prophylactic osseous spur excision. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Profound hypoxemia and hypotension during posterior spinal fusion in a spinal muscular atrophy child with severe scoliosis: a case report.

BACKGROUND: Anesthesia for spinal muscular atrophy (SMA) patients undergoing spinal deformity surgery is challenging. We report an unusual case of an SMA girl who developed severe intraoperative hypoxemia and hypotension during posterior spinal fusion related with surgical positioning. CASE PRESENTATION: A 13-yr-old girl diagnosed with SMA type 2, severe kyphoscoliosis and thoracic deformity was scheduled for elective posterior spinal fusion. She developed severe hypoxemia and profound hypotension intraoperatively in the prone position with surgical table tilted 45° to the right. Though transesophageal echocardiography (TEE) could not be performed due to limited mouth opening, her preoperative computed tomography revealed a severely distorted thoracic cavity with much reduced volume of the right side. A reasonable explanation was when the surgeons performed surgical procedure with the tilted surgical table, the pressure was directly put on the shortest diameter of the significantly deformed thoracic cavity, causing severe compression of the pulmonary artery, resulting in both hypoxemia and hypotension. The patient stabilized when the surgical table was tilted back and successfully went through the surgery in the leveled prone position. CONCLUSIONS: Spinal fusion surgery is beneficial for SMA patients in preventing scoliosis progression and improving ventilation. However, severe scoliosis and thoracic deformities put them at risk of both hemodynamic and respiratory instability during surgical positioning. When advanced monitoring like TEE is not practical intraoperatively, preoperative imaging may help with differential diagnosis, and guide the surgical positioning to minimize mechanical compression of the thoracic cavity, thereby helping the patient complete the surgery safely.

Regulation of the AGEs-induced inflammatory response in human periodontal ligament cells via the AMPK/NF-κB/ NLRP3 signaling pathway.

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE). It showed that advanced glycation end products modulate inflammatory responses in HPDLCs by activating NLRP1 and NLRP3 inflammasomes, which are further regulated through the NF-κB signaling pathway. Furthermore, AGEs synergize with NOD2, NLRP1, and NLRP3 inflammasomes to augment MDP-induced inflammation significantly.

[Retracted] NR4A1 promotes TNF­α­induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that fluorescence microscopy data shown in Fig. 2C were strikingly similar to data appearing in different form in Fig. 3G in a previously published paper by different authors at different research institutes [Jieensinue S, Zhu H, Li G, Dong K, Liang M and Li Y: Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK­Mff signaling pathways. BMC Cell Biology 19: 21, 2018]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 45: 151­161, 2020; DOI: 10.3892/ijmm.2019.4398].

Thoracic spondylotic myelopathy in diffuse idiopathic skeletal hyperostosis: a comparative study.

BACKGROUND: To explore the characteristics and clinical management of thoracic spinal stenosis with diffuse idiopathic skeletal hyperostosis (DISH). METHODS: The patients diagnosed with thoracic spondylotic myelopathy who underwent spinal decompression and fusion surgery in a single center between 2012 and 2020 were retrospectively analyzed. All the patients were followed up for at least 2 years. Patients were classified into DISH and non-DISH groups. Demographic, radiographic and clinical parameters were compared between the two groups. RESULTS: A total of 100 thoracic spondylotic myelopathy patients were included in the study. 22 patients were diagnosed with DISH. The proportion of male patients in the DISH group was higher, and the average BMI was larger. The incidence of upper thoracic vertebrae with ossification of posterior longitudinal ligament (OPLL) (P < 0.05) and lumbar spine with ossification of ligamentum flavum (OLF) was higher (P < 0.05) in DISH the group. The proportion of patients received staged surgery is higher in the DISH group (P < 0.1). There were no significant differences between the two groups in the amount of surgical bleeding, the ratio of cerebrospinal fluid leakage, the time duration of drainage tube placement and the JOA scores. CONCLUSION: Thoracic spinal stenosis with DISH occurred more in male patients with larger BMI. The posterior decompression and fusion surgery could achieve comparable satisfying clinical outcomes between DISH and non-DISH patients. More proportion of patients received staged surgery in the DISH group; the underline mechanism may be DISH caused more OPLL in the upper thoracic spine and more OLF in the lumbar spine because of mechanical stress.

Nucleus Pulposus Cells from Calcified Discs Promote the Degradation of the Extracellular Matrix through Upregulation of the GATA3 Expression.

OBJECTIVE: Disc calcification is strongly associated with disc degeneration; however, the underlying mechanisms driving its pathogenesis are poorly understood. This study aimed to provide a gene expression profile of nucleus pulposus cells (NPCs) from calcified discs, and clarify the potential mechanism in disc degeneration. METHODS: Primary NPCs were isolated from calcified and control discs (CAL-NPC and CON-NPC), respectively. The proliferation and extracellular matrix (ECM) metabolism capacities of the cells were evaluated using MTT and Western blotting, respectively. RNA sequencing was used to identify differentially expressed genes (DEGs) in the CAL-NPCs. The biological functions of the DEGs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network. The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated. RESULTS: The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs. In total, 375 DEGs were identified in the CAL-NPCs. The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways. GATA-binding protein 3 (GATA3) with the highest verified levels was selected for further studies. Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function, while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes. CONCLUSION: This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.

Revision Surgery After Spinal Fusion in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective Aanalysis of a Large Cohort of Cases. OBJECTIVES: To explore the rate and cause of revision surgery after spinal fusion in adolescent idiopathic scoliosis(AIS). METHODS: The patients diagnosed with AIS who underwent spinal fusion surgery in a single center from 2002 to 2018 were retrospectively analyzed. All the patients were followed up at least 2 years. The causes of revision surgery were analyzed and the incidence of revision surgery was counted. RESULTS: A total of 1816 AIS patients were included in the study. After an average of 8.5 years (range 3-18 years) follow-up, a total of 51 patients underwent 54 revision operations. The overall revision rate is 2.8%. The revision rate of combined approach (anterior and posterior) and anterior approach was 6.6% (8/122), and the revision rate of posterior approach was 2.5% (43/1694). The most common causes of revision were malposition of implants/implants failure (37%), followed by poor wound healing/ infection (23%). Spinal decompensation, adding on and proximal junctional kyphosis (PJK) accounted for 20%. The compensatory curve continued to worsen after selective fusion accounted for 14% and finally the discomfort with the implants accounted for 6%. CONCLUSIONS: The overall revision rate of spinal fusion for AIS is 2.8%. The implants and incision problems were the most common causes of revision surgeries.

Morphology characters of resected femoral and tibial surface in chinese population: intraoperative anthropometric study in patients at a tertiary hospital.

BACKGROUNDS: Mismatch between knee surface and prosthesis components is related to postoperative complications. Morphological differences between ethnicity and gender may affect prosthesis coverage. The purpose of this study is to describe morphological characters of resected knee surface (distal femur, proximal tibia) in the Chinese population, analyze the influence of gender and other demographical factors, and validate the effect of ethnic difference by calculating the coverage of Western-designed knee prostheses on Chinese knee surface. METHODS: Intraoperative anthropometries were performed during total knee arthroplasty performed by one single team. After screening out severe deformities and bone defects, data were separated via prosthesis system. Multiple linear regression and partial correlation analysis of morphological parameters on age, gender, height, weight were used to find out independent factors influencing morphology. Based on the 5 mm-tolerance in the prosthesis, simulation on scatter plots was brought out to calculate the prosthesis coverage to the resected bone surface. RESULTS: A total of 865 cases of total knee arthroplasty were involved in this study. Though gender differences were found in all knee morphological parameters regardless of the type of prosthesis, significant association was only found between gender and mediolateral width of femoral surface after adjusting demographical factors (p < 0.001). The two included prosthesis systems, Genesis-II and Scorpio NRG covered most cases in at least one dimension. Males had lower complete coverage and higher no coverage rate on femurs. Asymmetry prostheses had higher lateral coverage on tibiae. CONCLUSIONS: Based on our analysis, the only confirmed demographical factor in knee morphology is gender on femoral mediolateral length. Wider femoral prostheses for males may improve results of gender-specific prostheses. The overall fitness between Western-designed prostheses and Chinese knee surface is appliable, but the ratio of complete coverage is low. Further modification of prostheses systems can aim at the number of sizes and geometrical shapes.

Combined topical and intravenous administration of tranexamic acid further reduces postoperative blood loss in adolescent idiopathic scoliosis patients undergoing spinal fusion surgery: a randomized controlled trial.

BACKGROUND: To indicate whether combined topical and intravenous (IV) administration of tranexamic acid (TXA) could further reduce the blood loss after surgery for adolescent idiopathic scoliosis (AIS) compared with IV-TXA alone. METHODS: Ninety AIS patients who underwent posterior spinal fusion were prospectively randomized to combined group (IV + topical- TXA group) and IV-TXA alone group. TXA was infused at a loading dose of 1 g from the beginning of the surgery with a maintenance dose of 10 mg/kg/h until the wound was closed. In the combined group, 2 g TXA was injected retrogradely through a drain, while an equivalent amount of normal saline was injected in the IV-TXA alone group. The drain tube was clamped for 2 h in both groups. The amount of wound drainage and transfusion rates were analyzed. RESULTS: The drainage volume and duration of drain were significantly lower in the combined group compared with that in the IV-TXA alone group (372.0 ± 129.7 mL vs. 545.2 ± 207.7 mL, P < 0.001;64.7 ± 13.9 h vs. 82.0 ± 12.5 h, P < 0.001). Postoperative length of hospital stay was also significantly shorter in the combined group (6.5 ± 1.51 days vs. 7.95 ± 1.44 days, P < 0.05). Transfusion and complication rates were comparable between the two groups . CONCLUSIONS: IV injection of TXA combined with retrograde injection of TXA into a drain and clamping it for 2 h could further reduce the total volume of drainage in AIS patients who underwent spinal fusion surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900024177 , Registered 29 June 2019, http://www.chictr.org.cn/showproj.aspx?proj=40214.

Risk factors for blood transfusion in adolescent patients with scoliosis undergoing scoliosis surgery: a study of 722 cases in a single center.

BACKGROUND: To assess the risk factors for blood transfusion in a great number of adolescent cases with different types of scoliosis who received scoliosis surgery. METHODS: Data of patients who were diagnosed as scoliosis and received one-stage posterior correction and spinal fusion from January 2014 to December 2017 were prospectively collected and retrospectively analyzed. Patients' demographic characteristics, segments of spinal fusion, Cobb angle of the major curve,osteotomy pattern, preoperative and postoperative levels of hemoglobin, and allogeneic blood transfusion (ABT) were recorded and analyzed. RESULTS: In this study, 722 cases with adolescent scoliosis were included, of whom 32.8% (237/722) received ABT. Risk factors included diagnosis: neurofibromatosis (OR = 5.592), syndromic (OR = 3.029),osteotomy: Ponte osteotomy (OR = 5.997), hemivertebrae resection (OR = 29.171), pedicle subtraction osteotomy (PSO)(OR = 8.712), vertebral column resection (VCR)(OR = 32.265);fusion segments (OR = 1.224) and intraoperative blood loss (OR = 1.004). In the subgroup analysis of cases with idiopathic scoliosis, Ponte osteotomy (OR = 6.086), length of segments of spinal fusion (OR = 1.293), and intraoperative blood loss (OR = 1.001) were found as risk factors for ABT. Results of receiver operating characteristic (ROC) curve analysis revealed that length of segments of spinal fusion equal to 11.5 vertebrae was the best cutoff value for cases with idiopathic scoliosis who did not receive osteotomy in both ABT group and non-ABT group. In the subgroup analysis of congenital scoliosis, Ponte osteotomy (OR = 5.087), hemivertebra resection (OR = 5.457), PSO (OR = 4.055), VCR (OR = 6.940), and intraoperative blood loss (OR = 1.004) were risk factors for ABT. CONCLUSIONS: Method of diagnosis, osteotomy pattern, segments of spinal fusion, and intraoperative blood loss were risk factors for ABT in cases with adolescent scoliosis. In cases with idiopathic scoliosis, Ponte osteotomy and segments of spinal fusion longer than 11.5 vertebrae were risk factors for ABT. In cases with congenital scoliosis, osteotomy pattern was the main risk factor for ABT. LEVEL OF EVIDENCE: Level III.

LncRNA TUG1 promotes the intervertebral disc degeneration and nucleus pulposus cell apoptosis though modulating miR-26a/HMGB1 axis and regulating NF-κB activation.

AIMS: This study was to investigate the effect of TUG1 on apoptosis and ECM degradation of human degenerative intervertebral disc nucleus pulposus cells (NPCs) and its mechanism. METHODS: Human degenerative intervertebral disc NP tissues were obtained from 10 patients with lumbar disc herniation (LDH) who underwent lumbar spine surgery (IDD group), normal intervertebral disc NP tissues were obtained from 10 patients with lumbar vertebrae fractures (LVF group). RESULTS: The expression of TUG1 and HMGB1 protein in human degenerative disc NP tissues and NPCs was significantly increased, while the level of miR-26a was significantly decreased. Overexpression of TUG1 inhibited the proliferation while promoted apoptosis and ECM degradation of human degenerative intervertebral disc NPCs. Simultaneously, the effect of TUG1 knockdown on NPCs was opposite. Interestingly, TUG1 acted as an endogenous sponge to down-regulate the expression of miR-26a in NPCs by direct binding to miR-26a. Overexpression of miR-26a reversed the effects of TUG1 overexpression on apoptosis and ECM degradation. Additionally, HMGB1 was a target gene of miR-26a. The increased expression of HMGB1 induced by TUG1 overexpression could be reversed by the introduction of miR-26a mimic. Overexpression of TUG1 significantly upregulated the expression of p65 in the nucleus, while overexpression of TUG1 partially abolished the inhibition of NF-κB by QNZ pretreatment. CONCLUSION: TUG1 could promote the apoptosis and ECM degradation of degenerated intervertebral disc NPCs by regulating the miR-26a/HMGB1, which may be involved in the activation of NF-κB pathway.

Silencing of Long Non-coding RNA NEAT1 Upregulates miR-195a to Attenuate Intervertebral Disk Degeneration via the BAX/BAK Pathway.

BACKGROUND/AIMS: An increasing body of evidence has demonstrated that long non-coding RNAs (lncRNAs) play a vital regulatory role in intervertebral disk degeneration (IVDD). Nucleus enriched abundant transcript 1 (NEAT1), a novel cancer-related lncRNA, is associated with many malignancies, including ovarian cancer, and esophageal squamous cell carcinoma. Nevertheless, the role of NEAT1 in the progression of IVDD remains to be studied. Here, we explored the effect of NEAT1 on the progression of IVDD and the mechanisms involved. METHODS: An IVDD model was constructed in SD rats in vivo, and degeneration was induced by advanced glycation end product (AGE) in human nucleus pulposus cells (HNPC) in vitro. Quantitative real-time PCR was performed to detect the relative NEAT1 and miR-195a expressions and further confirmed the relationship between NEAT1 and miR-195a. Cell apoptosis was evaluated by TUNEL assay. The related mechanisms were explored by Western blot assay. RESULTS: The relative NEAT1 expression was significantly upregulated in the IVDD rat model and the denatured HNPC. Silencing of NEAT1 expression in HNPC significantly promoted the Collagen II and TIMP-1 expression induced by AGE while greatly suppressing the expressions of MMP-3 and cleaved caspase-3. Besides, downregulation of NEAT1 obviously reversed the AGE-induced apoptosis in HNPC. More interestingly, these effects of NEAT1 knockout on HNPC were largely reversed by silencing of miR-195a or overexpression of BAX under the AGE treatment. Mechanically, the direct combination of NEAT1 with miR-195a resulted in upregulation of MMP-3, cleaved caspase-3, BAX, and BAK, as well as downregulation of Collagen II and TIMP-1, which are associated with EMT and apoptosis. We also demonstrated similar results in the in vivo experiments. CONCLUSION: NEAT1 played its role in IVDD progression via partly by mediating the miR-195 expression and might be used as a potential target for IVDD therapy.

Mesenchymal stem cells induced regulatory dendritic cells from hemopoietic progenitor cells through Notch pathway and TGF-ß synergistically.

Mesenchymal stem cells (MSCs) are one of the attractive candidates in regenerative medicine of many clinical applications because of their low immunogenicity and immunomodulatory property. Our previous studies provided that mouse bone marrow-derived Sca-1+MSCs could drive the differentiation of regulatory DC (regDCs) (Scal-1+ BM-MSC-driven DC [sBM-DCs]) from hemopoietic progenitor cells (HPCs) and the Notch pathway played a critical role in maintaining the immunomodulatory property. However, the detailed mechanisms of their immunoregulatory capacity are not fully defined. In the present study, we show that BM-MSCs expressed high levels of Jagged 1 while sBM-DCs expressed high levels of Notch1. Jagged1 expressed on the surface of BM-MSCs initiated Notch signaling to maintain the immunomodulatory property of the sBM-DCs. The level of TGF-ß is high in MSCs, either alone or coculture with HPCs medium. TGF-ß plays a vital role in the proliferation and differentiation of sBM-DCs and inhibition of TGF-ß reduce the number and increase the percentage of CD34, CD117, CD135 of generation cells. Thus, MSCs induced the regDCs from HPCs via the Notch signaling pathway and TGF-ß synergistically. This study further broadens our understanding of the immunomodulatory mechanism and the potential therapeutic efficacy of MSCs.

Postoperative intravenous parecoxib sodium followed by oral celecoxib post total knee arthroplasty in osteoarthritis patients (PIPFORCE): a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVES: To evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety. DESIGN: Double-blind, pragmatic, randomised, placebo-controlled trial. SETTING: Four tertiary hospitals in China. PARTICIPANTS: 246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA). INTERVENTIONS: Patients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption. RESULTS: The cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group. CONCLUSIONS: The sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (ID: NCT02198924).

Anisodamine Maintains the Stability of Intervertebral Disc Tissue by Inhibiting the Senescence of Nucleus Pulposus Cells and Degradation of Extracellular Matrix via Interleukin-6/Janus Kinases/Signal Transducer and Activator of Transcription 3 Pathway.

Objectives: Anisodamine (ANI) has been used to treat a variety of diseases. However, the study of ANI in intervertebral disc degeneration (IVDD) is unclear. This study investigated the effects of ANI on degenerative nucleus pulposus cells (NPCs) and IVDD rats, and its possible mechanisms. Methods: Human nucleus pulposus cells (HNPCs) were treated with IL-1ß (20 ng/ml) to simulate IVDD, and an IVDD rat model was constructed. IL-1ß-induced HNPCs were treated with different concentrations (10, 20, or 40 µM) of ANI, and IVDD rats were also treated with ANI (1 mg/kg). Results: ANI treatment significantly reduced the apoptosis, caspase-3 and SA-ß-gal activities, and p53 and p21 proteins expression, while promoted telomerase activity and aggrecan and collagen II synthesis in IL-1ß-induced HNPCs. Moreover, the introduction of ANI inhibited the expression of IL-6, phosphorylation of JAK and STAT3, and nuclear translocation of p-STAT3 in Degenerated HNPCs. Additionally, the application of ANI abolished the effects of IL-6 on apoptosis, SA-ß-gal and telomerase activity, and the expression of p53, p21, aggrecan and collagen II proteins in degenerated HNPCs. Simultaneously, ANI treatment enhanced the effects of AG490 (inhibitor of JAK/STAT3 pathway) on IL-1ß-induced apoptosis, senescence and ECM degradation in HNPCs. Furthermore, ANI treatment markedly inhibited the apoptosis and senescence in the nucleus pulposus of IVDD rats, while promoted the synthesis of aggrecan and collagen II. ANI treatment obviously inhibited JAK and STAT3 phosphorylation and inhibited nuclear translocation of p-STAT3 in IVDD rats. Conclusion: ANI inhibited the senescence and ECM degradation of NPCs by regulating the IL-6/JAK/STAT3 pathway to improve the function of NPCs in IVDD, which may provide new ideas for the treatment of IVDD.

NR4A1 promotes TNF­α­induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway.

Nuclear receptor subfamily 4 group A member 1 (NR4A1)­induced chondrocyte death plays a critical role in the development of osteoarthritis through poorly defined mechanisms. The present study aimed to investigate the role of NR4A1 in regulating chondrocyte death in response to tumor necrosis factor­α (TNF­α) and cycloheximide (CHX) treatment, with a focus on mitochondrial fission and the AMP­activated protein kinase (AMPK) signaling pathway. The results demonstrated that NR4A1 was significantly upregulated in TNF­α and CHX exposed chondrocytes. Increased NR4A1 triggered mitochondrial fission via the AMPK/dynamin­related protein 1 (Drp1) pathway, resulting in mitochondrial dysfunction, and mitochondrial permeability transition pore (mPTP) opening­related cell death. Furthermore, excessive mitochondrial fission impaired chondrocyte migration through imbalance of F­actin homeostasis. Inhibiting NR4A1 attenuated TNF­α and CHX­induced mitochondrial fission and, thus, reduced mitochondrial dysfunction in chondrocytes, mPTP opening­related cell death and migration injury. Altogether, the present data confirmed that mitochondrial fission was involved in NR4A1­mediated chondrocyte injury via regulation of mitochondrial dysfunction, mPTP opening­induced cell death and F­actin­related migratory inhibition.

Effect of autophagy gene DRAM on proliferation, cell cycle, apoptosis, and autophagy of osteoblast in osteoporosis rats.

OBJECTIVE: The research aimed at detecting the autophagy level of osteoblast in osteoporosis rat, and investigating the effect of autophagy gene damage-regulated autophagy modulator (DRAM) on osteoblast proliferation, cell cycle, apoptosis, and autophagy. METHODS: The level of osteocalcin (OCN) and C-telopeptide (CTX) in serum of ovariectomized (OVX) rats was detected by enzyme-linked immunosorbent assay (ELISA). The Oil Red-O staining was used to observing bone histological changes. The messenger RNA level and protein expression level of Runt-related transcription factor 2 (Runx2; osteoblast markers) and other autophagy-related genes were revealed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The changes of autophagy in osteoblasts were detected by immunofluorescence staining. The following experiments were performed in osteoblasts of OVX rats through transfected with silencing DRAM to detecting cell proliferation, cell cycle, and apoptosis by Cell Counting Kit-8 assays and flow cytometry. RESULTS: The result of ELISA showed a significantly elevated of OCN and CTX in OVX rats as well a high fat content compared with sham-operated rats. The expression of Runx2 in bone of proximal tibia was higher by qRT-PCR and western blot analysis. The immunofluorescence staining and transmission electron microscope observe revealed that pcDNA3-DRAM could promote the autophagy in OVX rats. Besides that, overexpression of DRAM inhibited cell proliferation, promoted apoptosis, and enhanced autophagy in osteoblasts. The results of Oil Red-O staining indicated that overexpression of DRAM enhanced lipid accumulation in osteoporosis rats. CONCLUSIONS: The autophagy level of OVX rats was weakened, but overexpressed DRAM could increase the autophagy level of osteoblast, suppress proliferation, and induce apoptosis of osteoblast.

Adding Patella Resurfacing After Circumpatellar Electrocautery Did Not Improve the Clinical Outcome in Bilateral Total Knee Arthroplasty in Chinese Population: A Prospective Randomized Study.

BACKGROUND: In total knee arthroplasty (TKA), handling of the patella surface is still quite controversial. We carried out a prospective randomized study to compare circumpatellar electrocautery plus patella resurfacing vs circumpatellar electrocautery only in the single-staged bilateral TKA in Chinese population. METHODS: One hundred five patients diagnosed with late-staged osteoarthritis who received single-staged bilateral TKA were screened and 53 patients were included. All patients received the same posterior cruciate-stabilizing total knee prostheses. Patients were randomized to receive circumpatellar electrocautery plus patellar resurfacing or circumpatellar electrocautery only for the first TKA, and the second knee received the opposite treatment. All patients were followed for a minimum of 2 years. RESULTS: No differences were found with regard to Knee Society Score, Feller score, anterior knee pain, and revision rates. Fifty-two percent of patients had no preference with regard to pain and function, 27% of patients preferred the resurfacing plus circumpatellar electrocautery knee while 21% of the patients preferred the circumpatellar electrocautery only knee. The Insall-Salvati index and the patella tilt were a little smaller in the resurfacing group. One patient (2.1%) in the circumpatellar electrocautery group underwent a patella resurfacing revision for severe anterior knee pain and patella subluxation. CONCLUSION: Equivalent clinical results for circumpatellar electrocautery plus resurfacing and circumpatellar electrocautery alone of the patella in TKA were demonstrated in selective Chinese population with thick enough patella.

MicroRNA-23a-3p inhibitor decreases osteonecrosis incidence in a rat model.

The mechanism of steroid-associated femoral head necrosis remains unclear. The present study investigated the role of microRNA-23a-3p (miR-23a-3p) in the incidence of osteonecrosis in a rat model. An miR-23a-3p mimic, an inhibitor and a negative control were transfected into bone mesenchymal stem cells using a lentiviral vector, and then injected into the steroid-induced femoral head necrosis model. Osteonecrosis incidence was assessed by micro computed tomography and histopathology. Low-density lipoprotein receptor-related protein 5 (LRP-5) expression was assessed by immunohistochemistry. The results demonstrated the incidence of osteonecrosis decreased in the miR-23a-3p inhibitor group compared with the miR-23a-3p mimic group (18.2% vs. 75%; P<0.05). The ratio of bone volume/total volume and trabecular thickness were significantly increased in the miR-23a-3p inhibitor group compared with the miR-23a mimic group. The expression level of LRP-5 was higher in the miR-23a-3p inhibitor group. The present study indicated that miR may provide a novel and alternative approach for understanding the mechanism underlying steroid-associated necrosis of the femoral head.

Lenke 5C Curves in Adolescent Idiopathic Scoliosis: Anterior vs Posterior Selective Fusion.

BACKGROUND: The optimal treatment of Lenke 5C curves in adolescent idiopathic scoliosis is still unclear. OBJECTIVE: To compare the outcomes and the spontaneous correction behavior between anterior and posterior selective fusion techniques in a large case series. METHODS: Demographic and surgical data for patients with Lenke 5C curves treated with anterior or posterior fusion were collected from July 2002 to September 2011. Clinical assessment and radiographic parameters were compared preoperatively and postoperatively and at a minimum of 2 years of follow-up. RESULTS: Fifty-three Lenke 5C adolescent idiopathic scoliosis cases with an average follow-up of 4 years (range, 2-9.6 years) were included. The clinical scores were similar between the 2 groups. Postoperative major thoracic curvature changes were similar. The minor thoracic curve demonstrated a higher spontaneous correction rate in the posterior group. At follow-up, the minor thoracic curve showed a greater loss of correction in the posterior group, and finally both groups were comparable. Surgical time, intraoperative blood loss, and complications were comparable. A total of 5 patients had a final thoracic curve larger than the preoperative degrees. CONCLUSION: Selective fusion of the major thoracolumbar/lumbar curve in Lenke 5C adolescent idiopathic scoliosis can be achieved by anterior and posterior techniques. The spontaneous correction of the unfused thoracic curve was comparable after an average of 4 years follow-up.