Unilateral interlaminar fenestration on the convex side provides a reliable access for intrathecal administration of nusinersen in spinal muscular atrophy: a retrospective study.

BACKGROUND: As the first gene therapy for spinal muscular atrophy (SMA), nusinersen is supposed to be administrated via intrathecal injection regularly for a lifetime. However, for SMA patients with severe spinal deformities, bony fusion following posterior spinal instrumentation sets great obstacles for the application of nusinersen. Therefore, efforts have been devoted to the exploration of appropriate approach for nusinersen administration. This study aims to evaluate the safety and reliability of unilateral interlaminar fenestration on the convex side during spinal fusion surgery for intrathecal nusinersen injection in SMA. RESULTS: SMA patients receiving posterior spinal fusion and interlaminar fenestration in Peking Union Medical College Hospital from January 2020 to October 2021 were retrospectively analyzed. 13 patients were included. Of the 13 patients, 10 were classified into SMA type II and 3 into SMA type III. Distal fusion to pelvis was undertaken in 11 patients; while L5 was selected as the lowest instrumented vertebra in the other 2 patients. All patients received interlaminar fenestration on the convex side only with an area of about 15 mm × 20 mm. Fenestration at L2-L3 level was performed in 6 patients; while L3-L4 level was selected for windowing in the remaining 7 patients. 9 of the 13 patients received lumbar puncture and intrathecal nusinersen administration during the 1-year follow-up, with an accumulative total of 50 times. All injections were performed successfully under ultrasound guidance, with no one transferred to radiographic assistance. No severe complications occurred after injection. CONCLUSIONS: In SMA with severe scoliosis planning to receive posterior spinal fusion, unilateral lumbar interlaminar fenestration on the convex side provides a feasible and reliable access for intrathecal nusinersen administration after surgery.

Proteomic Comparison of Paraspinal Muscle Imbalance Between Idiopathic Scoliosis and Congenital Scoliosis.

OBJECTIVE: This study aims to compare the proteomic profiles of paraspinal muscle imbalance between idiopathic scoliosis (IS) and congenital scoliosis (CS). METHODS: Bilateral paraspinal muscles of 5 pairs of matched IS and CS patients were collected. Proteome patterns of paraspinal muscles were established. Differentially expressed proteins (DEPs) in paraspinal muscles between the convexity and the concavity were screened out. DEPs shared by both IS and CS and IS-specific DEPs were identified. Bioinformatic analyses of DEPs were performed. RESULTS: Among 105 DEPs identified in IS, 30 displayed predominant expression on the convexity, whereas other 75 exhibited predominant expression on the concavity. DEPs in IS were mainly enriched in calcium ion binding and DNA binding in gene ontology (GO) term and glycolysis/gluconeogenesis and purine metabolism in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Among 48 DEPs identified in CS, 25 were predominantly expressed on the convexity and 23 on the concavity. DEPs in CS were mainly enriched in receptor activity and immune response in GO term and glycolysis/gluconeogenesis and cellular senescence in KEGG pathway. Comparison of DEPs between IS and CS identified only 8 proteins shared by both types of scoliosis. Among the 97 IS-specific DEPs, 28 were predominantly expressed on the convexity and 69 on the concavity. IS-specific genes were enriched in calcium ion binding and protein glycosylation in GO term and glycolysis/gluconeogenesis and hypertrophic cardiomyopathy in KEGG pathway. CONCLUSION: IS and CS exhibit proteomic imbalance in bilateral paraspinal muscles but share few similarities. Paraspinal muscle imbalance in IS might not be the consequence of spinal deformities.

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.

Comparison of blood loss between tranexamic acid-soaked absorbable Gelfoam and topical retrograde injection via drainage catheter plus clamping in cervical laminoplasty surgery.

BACKGROUND: To compare the safety and efficacy of tranexamic acid (TXA)-soaked absorbable Gelfoam and the retrograde injection of TXA through a drain with drain-clamping in degenerative cervical laminoplasty patients. METHODS: Patients were assigned into either TXA retrograde injection (TXA-RI), TXA-soaked absorbable Gelfoam (TXA-Gel), or control groups. The demographics, operative measurements, volume and length of drainage, length of hospital stay, complete blood cell count, coagulopathy, postoperative complications, and blood transfusion were recorded. RESULTS: We enrolled 133 patients, with 44, 44, and 45 in the TXA-RI, TXA-Gel, and control groups, respectively. The baseline characteristics did not differ significantly among the three groups. The TXA-RI group exhibited a lower volume and length of postoperative drainage compared to the TXA-Gel and control groups (126.60 ± 31.27 vs. 156.60 ± 38.63 and 275.45 ± 75.27 mL; 49.45 ± 9.70 vs 58.70 ± 10.46 and 89.31 ± 8.50 hours, all P < 0.01). The TXA-RI group also had significantly shorter hospital stays compared to the control group (5.31 ± 1.18 vs 7.50 ± 1.25 days, P < 0.05) and higher hemoglobin and hematocrit levels (12.58 ± 1.67 vs 11.28 ± 1.76 g/dL; 36.62 ± 3.66% vs 33.82 ± 3.57%, both P < 0.05) at hospital discharge. In the TXA-RI and TXA-Gel groups, the D-dimmer (DD) and fibrinogen (FIB) were significantly lower than those in the control group after surgery (P < 0.05). None of the patients required blood transfusion. No complications, including thromboembolic events, were reported. CONCLUSION: Topical retrograde injection of TXA through a drain with drain-clamping at the conclusion of unilateral posterior cervical expansive open-door laminoplasty may effectively reduce postoperative blood loss and the length of hospital stays without increasing postoperative complications.

Phosphoglycerate kinase 1 silencing by a novel microRNA microRNA-4523 protects human osteoblasts from dexamethasone through activation of Nrf2 signaling cascade.

Nuclear-factor-E2-related factor 2 (Nrf2) cascade activation can ameliorate dexamethasone (DEX)-induced oxidative injury and death in human osteoblasts. Phosphoglycerate kinase 1 (PGK1) depletion is shown to efficiently activate Nrf2 signaling by inducing methylglyoxal modification of Kelch-like ECH-associated protein 1 (Keap1). We here identified a novel PGK1-targeting microRNA: microRNA-4523 (miR-4523). RNA fluorescent in situ hybridization, RNA pull-down, and Argonaute-2 RNA immunoprecipitation results confirmed a direct binding between miR-4523 and PGK1 mRNA in primary human osteoblasts and hFOB1.19 osteoblastic cells. Forced overexpression of miR-4523, using a lentiviral construct, robustly decreased PGK1 3'-UTR (untranslated region) luciferase activity and downregulated its expression in human osteoblasts and hFOB1.19 cells. Furthermore, miR-4523 overexpression activated the Nrf2 signaling cascade, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization, and its nuclear translocation as well as transcription activation of Nrf2-dependent genes (NQO1, GCLC, and HO1) in human osteoblasts. By expressing a UTR-null PGK1 construct, miR-4523 overexpression-induced Nrf2 cascade activation was however largely inhibited. Importantly, DEX-induced reactive oxygen species production, oxidative injury, and cell apoptosis were significantly attenuated by miR-4523 overexpression in human osteoblasts and hFOB1.19 cells. Such actions by miR-4523 were abolished by Nrf2 shRNA or knockout, but mimicked by PGK1 knockout (using CRISPR/Cas9 method). In PGK1 knockout human osteoblasts, miR-4523 overexpression failed to further increase Nrf2 cascade activation and offer osteoblast cytoprotection against DEX. Significantly, miR-4523 is downregulated in human necrotic femoral head tissues of DEX-taking patients. Together, PGK1 silencing by miR-4523 protected human osteoblasts from DEX through activation of the Nrf2 signaling cascade.

DCAF1-targeting microRNA-3175 activates Nrf2 signaling and inhibits dexamethasone-induced oxidative injury in human osteoblasts.

Activation of nuclear-factor-E2-related factor 2 (Nrf2) signaling can protect human osteoblasts from dexamethasone-induced oxidative injury. DDB1 and CUL4 associated factor 1 (DCAF1) is a novel ubiquitin E3 ligase for Nrf2 protein degradation. We identified a novel DCAF1-targeting miRNA, miR-3175. RNA pull-down, Argonaute 2 RNA-immunoprecipitation, and RNA fluorescent in situ hybridization results confirmed a direct binding between miR-3175 and DCAF1 mRNA in primary human osteoblasts. DCAF1 3'-untranslated region luciferase activity and its expression were significantly decreased after miR-3175 overexpression but were augmented with miR-3175 inhibition in human osteoblasts and hFOB1.19 osteoblastic cells. miR-3175 overexpression activated Nrf2 signaling, causing Nrf2 protein stabilization, antioxidant response (ARE) activity increase, and transcription activation of Nrf2-dependent genes in human osteoblasts and hFOB1.19 cells. Furthermore, dexamethasone-induced oxidative injury and apoptosis were largely attenuated by miR-3175 overexpression in human osteoblasts and hFOB1.19 cells. Importantly, shRNA-induced silencing or CRISPR/Cas9-mediated Nrf2 knockout abolished miR-3175 overexpression-induced osteoblast cytoprotection against dexamethasone. Conversely, DFAC1 knockout, by the CRISPR/Cas9 method, activated the Nrf2 cascade and inhibited dexamethasone-induced cytotoxicity in hFOB1.19 cells. Importantly, miR-3175 expression was decreased in necrotic femoral head tissues of dexamethasone-taking patients, where DCAF1 mRNA was upregulated. Together, silencing DCAF1 by miR-3175 activated Nrf2 signaling to inhibit dexamethasone-induced oxidative injury and apoptosis in human osteoblasts.

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.

Surgical Scoliosis Correction in Chiari-I Malformation with Syringomyelia Versus Idiopathic Syringomyelia.

BACKGROUND: Both patients with Chiari-I malformation (CIM) with syringomyelia and those with idiopathic syringomyelia (ISm) have a syrinx and can have scoliosis as well. However, there is no literature regarding differences between CIM and ISm in terms of radiographic outcomes and surgical complications after posterior fusion, to our knowledge. The aim of the present study was to compare radiographic features, clinical outcomes, and surgical complications after posterior spinal fusion between patients with CIM-associated scoliosis and those with ISm-associated scoliosis. METHODS: One hundred and twenty patients with syringomyelia-associated scoliosis were retrospectively analyzed. Twenty-one patients with scoliosis secondary to CIM were enrolled and matched by sex, age, and the Cobb angle of the scoliotic curve with 21 patients with scoliosis secondary to ISm. All patients underwent 1-stage posterior fusion surgery. Coronal and sagittal radiographic parameters were evaluated before surgery, immediately after surgery, and at the final follow-up (at least 2 years). We also collected data regarding syringeal features, neurological deficits, intraoperative neuromonitoring, and complications. RESULTS: Sex, age, preoperative coronal/sagittal scoliosis parameters, and neurological deficits were similar between the matched CIM and ISm groups. On average, the CIM group had a longer syrinx (12.3 ± 3.6 versus 8.9 ± 4.5 vertebral levels, p = 0.010) than the ISm group. The CIM and ISm groups showed similar correction rates for primary curves (70.9% ± 10.6% versus 69.5% ± 16.3%, p = 0.739). There were no significant differences in coronal/sagittal correction, intraoperative neuromonitoring abnormalities, surgical complications, or Scoliosis Research Society-22 questionnaire scores between the 2 groups. CONCLUSIONS: Despite matched demographic and scoliotic coronal parameters, patients with CIM had longer syrinxes compared with patients with ISm. One-stage posterior fusion achieved comparable clinical and radiographic outcomes for both CIM- and ISm-associated scoliosis without significant differences in neurological complications. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Circular RNA HIPK3 downregulation mediates hydrogen peroxide-induced cytotoxicity in human osteoblasts.

Hydrogen peroxide (H2O2) induces oxidative injury to human osteoblasts. The expression and potential function of circular RNA HIPK3 (circHIPK3) in H2O2-treated human osteoblasts were tested. We show that H2O2 significantly downregulated circHIPK3 in OB-6 cells and primary human osteoblasts. Furthermore, circHIPK3 levels were decreased in the necrotic femoral head tissues of dexamethasone-treated patients. In OB-6 osteoblastic cells and primary human osteoblasts, forced overexpression of circHIPK3 by a lentiviral construct alleviated H2O2-induced viability reduction, cell death and apoptosis. Contrarily, circHIPK3 silencing by targeted shRNA potentiated H2O2-induced cytotoxicity in OB-6 cells and primary human osteoblasts. Moreover, circHIPK3 downregulation by H2O2 induced miR-124 accumulation in OB-6 cells and primary human osteoblasts. On the contrary, miR-124 inhibition by transfection of the miR-124 inhibitor protected human osteoblasts from H2O2. Importantly, forced overexpression of miR-124 by transfection of the miR-124 mimic induced significant cytotoxicity in OB-6 cells and primary human osteoblasts. H2O2 downregulated miR-124's targets, cyclin dependent kinase 6 and Rho-Associated Protein Kinase 1, in human osteoblasts. In conclusion circHIPK3 downregulation mediates H2O2-induced cytotoxicity in human osteoblasts.

Topical Injection of Tranexamic Acid via a Drain Plus Drain-Clamping to Reduce Blood Loss in Degenerative Lumbar Scoliosis Surgery.

OBJECTIVE: The aim of the present study was to investigate whether an innovative way of administering tranexamic acid (TXA), that is, injecting it retrogradely through the drain and clamping it for 1 h, can reduce postoperative bleeding after degenerative lumbar scoliosis surgery. METHODS: Sixty degenerative lumbar scoliosis patients who underwent posterior lumbar decompression with fusion of three or more levels were retrospectively enrolled and categorized into three groups (TXA, Gelfoam, and control groups). The demographic distribution, operative parameters, length and amount of Hemovac drainage, blood transfusion rate, length of stay, laboratory results (complete blood count and coagulogram), and the postoperative complications were collected and analyzed. RESULTS: The age of patients in the Gelfoam group was significantly younger than in the TXA and control groups (59.75 ± 6.95 vs 66.10 ± 8.80, P = 0.016 and 59.75 ± 6.95 vs 67.90 ± 5.33, P = 0.000, respectively). There were no significant differences in sex, body mass index, comorbid medical status, and operation level between each of the two groups. The three groups did not differ significantly in estimated blood loss during surgery, the mean red blood cell transfusion requirement during hospitalization, and the entire perioperative allogenic blood transfusion rate. The postoperative total blood loss and total drainage were lower in the TXA group than in the control group (1027.14 ± 466.56 vs 1390.07 ± 314.85 mL, P = 0.006; 322.20 ± 187.32 vs 605.50 ± 184.70 mL, P = 0.000, respectively). The length of drainage retention in the TXA group was significantly shorter than in the Gelfoam and control groups (46.10 ± 9.00 vs 68.00 ± 12.31 h, P = 0.000 and 46.10 ± 9.00 vs 76.40 ± 10.97 h, P = 0.000, respectively). The TXA and Gelfoam groups also had significantly shorter hospital stays than the control group (7.50 ± 0.95 vs 9.80 ± 2.44 days, P = 0.000, and 7.90 ± 1.16 vs 9.80 ± 2.44 days, P = 0.003, respectively). At discharge, the mean hemoglobin and hematocrit level were significantly higher in the TXA group compared with the control group (11.77 ± 1.78 g/dL vs 10.67 ± 0.94 g/dL, P = 0.002; 34.82 ± 3.57% vs 31.79 ± 3.85%, P = 0.014). No significant difference was identified with respect to prothrombin time, activated partial thromboplastin time, and D-dimmer among groups (P > 0.05). The three groups were comparable in wound problem incidences. Symptomatic deep vein thrombosis and pulmonary embolism were not observed in this study. CONCLUSION: Topical injection of TXA retrogradely via a drain at the end of a degenerative lumbar scoliosis operation and clamping the drain for an hour can effectively decrease the postoperative blood loss and the length of hospitalization without increasing the complication rate.

Comparison of Radiological Features and Clinical Characteristics in Scoliosis Patients With Chiari I Malformation and Idiopathic Syringomyelia: A Matched Study.

STUDY DESIGN: Retrospective study. OBJECTIVE: To compare syrinx characteristics, scoliotic parameters, and neurological deficits between Chiari I malformation (CIM) and idiopathic syringomyelia (IS) in the scoliotic population. SUMMARY OF BACKGROUND DATA: CIM and IS are common in neuromuscular scoliosis patients; however, differences in syrinx characteristics, scoliotic parameters, and neurological deficits between CIM and IS are unclear. METHODS: Thirty-six patients with scoliosis secondary to CIM were enrolled retrospectively and matched with 36 IS patients for sex, age, scoliosis classification, and Cobb angle. Information on radiographic features of scoliosis and syrinx and neurological deficits was systematically collected. RESULTS: Sex, age, and coronal, and sagittal scoliosis parameters did not differ between the CIM and IS groups. The CIM group had a longer syrinx (12.9 ±â€Š4.0 vertebral levels vs. 8.7 ±â€Š5.5 vertebral levels, P < 0.001), a higher cranial extent (3.6 ±â€Š2.2 vs. 5.2 ±â€Š3.5, P = 0.027), and a lower caudal extent (15.6 ±â€Š2.9 vs. 13.0 ±â€Š4.6, P = 0.006) than the IS group, despite no differences in syrinx/cord (S/C) ratio or syrinx classification. No differences in neurological deficits were identified between the CIM and IS patients. CONCLUSION: With demographic and scoliotic coronal parameters matched, the CIM patients had a longer syrinx, located at a higher cranial and lower caudal level, compared with the IS group. No significant differences in syrinx S/C ratio, sagittal features of scoliosis, or neurological deficits were detected between the two groups. LEVEL OF EVIDENCE: 3.

PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone.

Activation of nuclear-factor-E2-related factor 2 (Nrf2) cascade can alleviate dexamethasone (DEX)-induced oxidative injury and death of human osteoblasts. A recent study has shown that phosphoglycerate kinase 1 (PGK1) inhibition/depletion will lead to Kelch-like ECH-associated protein 1 (Keap1) methylglyoxal modification, thereby activating Nrf2 signaling cascade. Here, in OB-6 osteoblastic cells and primary human osteoblasts, PGK1 silencing, by targeted shRNA, induced Nrf2 signaling cascade activation, causing Nrf2 protein stabilization and nuclear translocation, as well as increased expression of ARE-dependent genes (HO1, NQO1, and GCLC). Functional studies demonstrated that PGK1 shRNA largely attenuated DEX-induced oxidative injury and following death of OB-6 cells and primary osteoblasts. Furthermore, PGK1 knockout, by the CRISPR/Cas9 method, similarly induced Nrf2 signaling activation and protected osteoblasts from DEX. Importantly, PGK1 depletion-induced osteoblast cytoprotection against DEX was almost abolished by Nrf2 shRNA. In addition, Keap1 shRNA mimicked and nullified PGK1 shRNA-induced anti-DEX osteoblast cytoprotection. At last we show that PGK1 expression is downregulated in human necrotic femoral head tissues of DEX-taking patients, correlating with HO1 depletion. Collectively, these results show that PGK1 depletion protects human osteoblasts from DEX via activation of Keap1-Nrf2 signaling cascade.

Revision Surgery after Percutaneous Endoscopic Transforaminal Discectomy Compared with Primary Open Surgery for Symptomatic Lumbar Degenerative Disease.

OBJECTIVE: To evaluate the clinical outcome of reoperation after percutaneous endoscopic lumbar discectomy (PELD) as compared with primary spinal decompression and fusion. METHODS: A retrospective study from December 2014 to December 2017 was conducted at Peking Union Medical College Hospital and comprised 39 patients with symptomatic lumbar degenerative disease (LDD): 13 post-PELD who underwent reoperation (revision surgery group) and 26 who received primary spinal decompression and fusion (primary open surgery group). The two groups were compared regarding: operative time, blood loss, transfusion, hospitalization, postoperative visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, Japanese Orthopedic Association (JOA) improvement rate, and postoperative complications. The Mann-Whitney U-test was applied to analyze continuous parameters, and the χ2 -test for categorical parameters. Fisher's exact test was used for small data subsets. RESULTS: There was no statistically significant difference between the two groups in mean age (52.7 years vs 52.9 years), gender ratio (6 men-to-7 women vs 12 men-to-14 women), body mass index, medical history, preoperative diagnosis, or surgical spine level (P > 0.05). The mean operative time of the revision surgery group was significantly longer than that of the primary open surgery group (160.0 min vs 130.2 min, P < 0.05). The revision surgery group also had a significantly higher mean estimated blood loss, postoperative drainage, and length of hospital stay (P < 0.05). However, no significant differences were found between the two groups in terms of hemoglobin and hematocrit values, preoperatively and postoperatively. The rate of transitional neurological irritation was higher in the revision surgery group (61.5% vs 3.8%; P < 0.05), as was intraoperative durotomy and cerebrospinal fluid leakage (30.8% vs 3.8%, P < 0.05). At 1 month, the VAS and ODI scores of the primary open surgery group were significantly better than those of the revision surgery group, while the improvement in JOA scores was similar. After 6 and 12 months' follow-up, the VAS and ODI scores and the rates of JOA improvement were comparable. CONCLUSION: Patients with LDD who received primary spinal decompression and fusion experienced lower rates of perioperative complications and shorter hospitalization compared with patients who underwent revision surgery after PELD, but the clinical outcomes at the last follow-up of both groups were satisfactory.

Gossypol Promotes Wnt/ß-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis.

Osteoporosis is one of the most frequent diseases related with age. Previously, we have reported a novel potential drug, gossypol, for the treatment of osteoporosis through its regulation of Wnt/ß-catenin signaling. This study aims to identify the detailed mechanism of gossypol in human osteoporosis. Mice injected with gossypol were subjected for RNA-seq analysis and the transcription level of WIF1 was shown to be decreased dramatically in gossypol-treated mice, which was further confirmed by qRT-PCR and western blot analysis. Luciferase reporter assay showed gossypol inhibited the activity of WIF1 and the methylation of WIF1 was significantly upregulated, evidenced by ChIP assay. Cell viability assays demonstrated that gossypol promoted cell proliferation while cotreatment with WIF1 expressing plasmid reversed the effect in a dose- and time-dependent manner. Similarly, cell apoptotic assays and TUNEL assays showed gossypol suppressed cell apoptosis, which was revised by WIF1 overexpression. The mouse model suggested gossypol injection ameliorated osteoporosis, while coinjection of AAV5-WIF1 eliminated the protection effects of gossypol, as evidenced by H&E staining, serum osteocalcin level, serum OPG level, serum RANKL level, bone density, ultimate strength, and postyield displacement. This study is a supplement to the former publication, which reinforced the protection effect of gossypol in human osteoporosis.

LncRNA-SULT1C2A regulates Foxo4 in congenital scoliosis by targeting rno-miR-466c-5p through PI3K-ATK signalling.

Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non-coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)-induced CS. Bioinformatics analysis and quantitative real-time PCR (qRT-PCR) indicated that SULT1C2A expression was down-regulated in VAD group, accompanied by increased expression of rno-miR-466c-5p but decreased expression of Foxo4 and somitogenesis-related genes such as Pax1, Nkx3-2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno-miR-466c-5p expression by direct binding, and rno-miR-466c-5p inhibited Foxo4 expression by binding to its 3' untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno-miR-466c-5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT-PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS. Thus, SULT1C2A may be a potential target for treating CS.

Modified PUMC classification for adolescent idiopathic scoliosis.

BACKGROUND: The original Peking Union Medical College (PUMC) classification of adolescent idiopathic scoliosis (AIS) is one system to combine each type with corresponding surgical fusion guidance, presenting comparable interobserver reliability, and reproducibility with Lenke classification. However, during its application in previous over 10 years, we found 2 main problems of this classification, which required modification. PURPOSE: (1) To evaluate the interobserver and intraobserver reliability, (2) to assess the effects of the added fusion criteria of proximal thoracic (PT) curve on improving postoperative shoulder balance of the modified PUMC classification of AIS. STUDY DESIGN/SETTING: Retrospective analysis of our AIS cohort and prospective validation of its effectiveness. PATIENT SAMPLE: Fifty sets of preoperative radiographs of AIS patients were randomly chosen from our AIS database. Furthermore, 46 consecutive AIS cases with PT curve were enrolled who underwent surgeries in our center from July 2007 to July 2013, with at least 2-year follow-up. OUTCOME MEASURES: The classification results of 50 sets of preoperative radiographs by 5 surgeons. The shoulder balance was evaluated using radiographic shoulder height. METHODS: Five surgeons independently evaluated and classified presurgical radiographs of 50 AIS patients based on the modified PUMC classification. Inter- and intraobserver reliabilities were calculated. Furthermore, the post-op shoulder balance was investigated in 46 consecutive cases of AIS with PT curve who were treated strictly based on the modified PUMC classification. RESULTS: The Kappa coefficients of inter- and intraobserver reliability of the overall modified PUMC classification are 0.889 and 0.865, respectively. The Kappa coefficients of inter- and intraobserver reliability for the type II are 0.791 and 0.746, respectively. In addition, the shoulder balance rate of the 46 AIS patients with PT curve at the final follow-up was 95.7%. CONCLUSIONS: Modified PUMC classification presents incremental improvement compared to our original published version, with high interobserver and intraobserver reliability and better performance of postoperative shoulder balance. Furthermore, the modified PUMC classification provides corresponding surgical fusion guidance for each subtype. Multicenter prospective studies with larger samples are still needed to further improve this system.

Preliminary Study of a New Growing Rod System in Immature Swine Model.

BACKGROUND: Growing rod techniques have been demonstrated to be a valuable treatment in early-onset scoliosis; however, repeated surgeries and general anesthesia cannot be avoided. METHODS: This study included 12 immature swine that were randomly assigned to receive either a novel growing rod system (experimental group) or a traditional growing rod system (control group). Lengthening was undertaken at 4-week intervals, for a total observation period of 12 weeks. Radiography, computed tomography, and motion analysis of the spine were conducted to evaluate rod extension, growth and nonfusion of the spine, and fixation. RESULTS: One swine (control group) was excluded from the analysis because of a deep wound infection at 1 week after the initial operation. No complications were observed in the remaining 11 swine. In the experimental group, the average lengthening operation lasted 12.1 ± 3.1 minutes, and average incision length was 1.1 ± 0.2 cm; both values were significantly less compared with the control group (P < 0.001). No significant between-group differences in mean trunk length, body mass, or thickness of cephalad-instrumented or caudad-instrumented vertebrae and intervertebral disks were present before the initial operation or at the final assessment (12 weeks after operation; P > 0.05). Spinal growth and motion of instrumented spinal segments were conserved. CONCLUSIONS: The novel growing rod system is safe and effective in immature swine, preserving spine growth potential and involving less surgical trauma.

SPOCD1 promotes cell proliferation and inhibits cell apoptosis in human osteosarcoma.

Osteosarcoma is the most common type of malignant bone tumors that typically affects adolescents and children. The spen paralogue and orthologue C­terminal domain containing 1 (SPOCD1) is a newly identified molecule that has been indicated to discriminate progressive from non­progressive bladder cancers. However, the role of SPOCD1 in human solid tumors remains largely unknown. In the present study, SPOCD1 was upregulated in clinical osteosarcoma tissues compared with adjacent non­cancerous tissues. Furthermore, SPOCD1 was upregulated in osteosarcoma cell lines and expression was particularly increased in highly invasive cells MG63 and SAOS2. Further investigation revealed that downregulation of SPOCD1 inhibited the MG63 and SAOS2 osteosarcoma cell colony formation and proliferation capacity. In addition, cell apoptosis was promoted by knockdown of SPOCD1 in MG63 and SAOS2 cells. These effects were confirmed by measuring the Ki67 and PCNA expression. In addition, SPOCD1 positively regulated the expression of vascular endothelial growth factor A (VEGF­A). Knockdown of VEGF­A blunted SPOCD1 downregulation­mediated inhibition of cell proliferation and induction of cell apoptosis. These results suggested that SPOCD1 may act as a pro­oncogenic factor in osteosarcoma. Inhibition of VEGF may aid in treating osteosarcoma in clinic.

Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis.

Osteoporosis is among the most common forms of age-related diseases, especially for females, which has been a grave public health problem. Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatment of osteoporosis. Treatments of ovariectomy-induced osteoporosis mice with gossypol significantly increased serum osteocalcin and osteoprotegerin (OPG) levels; meanwhile they decreased serum RANKL levels. Microcomputed tomography (microCT) analysis showed that treatment of gossypol improved bone density and strength and decreased bone postyield displacement for both medullar and cortical bones. In vitro experiments also showed that gossypol increased cell viability in a time- and dose-dependent manner. Furthermore, incubation of the osteoblast MC3T3-E1 cells with gossypol inhibited cell apoptosis through intrinsic apoptotic pathway as evidenced by the Annexin V/PI assay, TUNEL assay, biochemical analysis, and western blot assays. Moreover, the classical Wnt/ß-catenin signaling pathway was found to be regulated by gossypol treatments. Inhibition of Wnt/ß-catenin signaling reversed the prevention effects of gossypol in osteoporosis. Our findings provided novel clues for the treatment of osteoporosis in clinic.