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MicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.

BackgroundIntervertebral disc degeneration (IDD) can induce profound global socioeconomic burdens. Recent studies have suggested that circular RNAs might have crucial functions in the progression of IDD. The purpose of this study was to identify a specific circular RNA and to investigate its regulatory mechanism in IDD.MethodsCircGLCE was selected after microarray analyses and was further analysed by RT-qPCR and FISH. After silencing CircGLCE, its function was assessed with RT-qPCR, immunofluorescence analysis and flow cytometry. Based on Sanger sequencing, miR-587 was identified as a direct target of CircGLCE, and it was further examined with RNA pulldown assays, RT-qPCR, dual luciferase assays and FISH. After silencing CircGLCE or miR-587, western blotting, immunofluorescence analysis, and flow cytometry were conducted. STAP1 was assessed by RT-qPCR and luciferase assay, and experiments with silenced and overexpressed miR-587 were performed. A rescue experiment was also included. In an IDD rat model, the in vivo effects of overexpressing CircGLCE on IDD were analysed with imaging techniques, TUNEL staining, FISH, western blotting, H&E staining and immunohistochemistry.ResultsCircGLCE was found to stably exist in the cytoplasm of nucleus pulposus (NP) cells. It was downregulated in IDD. Knockdown of CircGLCE promoted apoptosis and induced the expression of matrix-degrading enzymes in NP cells. CircGLCE served as a miR-587 sponge in NP cells. Inhibiting miR-587 counteracted the IDD-enhancing effect caused by silencing CircGLCE. STAP1 served as the miRNA target that mediated the functions of miR-587. Overexpressing CircGLCE alleviated IDD in vivo.ConclusionsCircGLCE attenuates IDD by regulating the apoptosis of NP cells and by regulating ECM degradation through the targeting of miR-587/STAP1. CircGLCE may be a potential therapeutic target for IDD treatments.

It is obvious that epigenetic processes influence the evolution of intervertebral disc degeneration (IDD). However, its molecular mechanisms are poorly understood. Therefore, we tested the hypothesis that IGFBP5, a potential regulator of IDD, modulates IDD via the ERK signalling pathway. We showed that IGFBP5 mRNA was significantly down‐regulated in degenerative nucleus pulposus (NP) tissues. IGFBP5 was shown to significantly promote NP cell proliferation and inhibit apoptosis in vitro, which was confirmed by MTT, flow cytometry and colony formation assays. Furthermore, IGFBP5 was shown to exert its effects by inhibiting the ERK signalling pathway. The effects induced by IGFBP5 overexpression on NP cells were similar to those induced by treatment with an ERK pathway inhibitor (PD98059). Moreover, qRT‐PCR and Western blot analyses were performed to examine the levels of apoptosis‐related factors, including Bax, caspase‐3 and Bcl2. The silencing of IGFBP5 up‐regulated the levels of Bax and caspase‐3 and down‐regulated the level of Bcl2, thereby contributing to the development of human IDD. Furthermore, these results were confirmed in vivo using an IDD rat model, which showed that the induction of Igfbp5 mRNA expression abrogated the effects of IGFBP5 silencing on intervertebral discs. Overall, our findings elucidate the role of IGFBP5 in the pathogenesis of IDD and provide a potential novel therapeutic target for IDD.

The interaction among different sizes of cracks in materials is one of the key factors leading to the damage of brittle materials. Based on the Kachanov method, the expressions for the stress intensity factors of two collinear cracks with unequal length were obtained and the interaction effect was analyzed. A compression test of a cement mortar specimen containing two cracks and numerical analysis usingRFPA2Dwere performed. The results indicate that the crack interaction can almost be neglected when the crack distance reaches the length of the large crack; the two respective collinear cracks in the specimen grow and do not affect each other when the crack distance reaches the large crack length. The results of compression test and numerical analysis are both in agreement with the theoretical result.

Study design Retrospective radiographical clinical study. Objective To investigate the incidence and risk factors of coronal imbalance (CI) after three-column osteotomy (3-CO) in patients with thoracolumbar congenital kyphoscoliosis (CKS). Summary of background data The incidence and risk factors of postoperative CI have been reported in adolescent idiopathic and degenerative lumbar scoliosis. However, limited data exists for patients with CKS after 3-CO. Methods We reviewed a consecutive series of patients with CKS who underwent posterior-only 3-CO. Coronal curve patterns were classified according to absolute C7 translation values into: Type A, C7 translation is less than 30 mm; Type B, C7 translation more than or equal to 30 mm and C7 plumb line (C7PL) shifted to the concave side of the main curve; and Type C, C7 translation more than or equal to 30 mm and C7PL shifted to the convex side. CI was defined as C7 translation on either side more than or equal to 30 mm. According to C7 translation at the latest follow-up, patients was subdivided into an imbalanced group and a balanced group. Results One-hundred-thirty patients (mean age, 17.7 ± 5.2 yr) were recruited. The mean follow-up was 41.3 ± 18.5 months. Twenty-six patients (20%) were identified as having CI at the latest follow-up. Compared with the balanced group, the imbalanced group had a larger proportion of preoperative Type C pattern, higher main curve correction, and greater lowest instrumented vertebra (LIV) tilt before and after surgery. Multiple logistic regression showed that risk factors for CI were preoperative type C pattern, preoperative LIV tilt more than or equal to 23.5° and immediate postoperative LIV tilt more than or equal to 12.3°. Conclusion The incidence of CI in patients with CKS after 3-CO was 20%. A preoperative type C pattern, preoperative LIV tilt more than or equal to 23.5°, and immediate postoperative LIV tilt more than or equal to 12.3° were found to be associated with CI at the latest follow-up. Level of evidence 3.

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population., Graphical abstract, Zhou et al. isolate 54 potent neutralizing antibodies from convalescent COVID-19 patients, revealing diverse immunoglobulin gene usage and convergent epitope targeting of neutralizing antibody responses to SARS-CoV-2. Vaccines that effectively present the RBD receptor binding site will likely elicit neutralizing antibody responses in a large fraction of the population.

Bone cancer pain (BCP) was associated with microRNA dysregulation. In this study, we intended to clarify the potential role of miR-135-5p in a BCP mouse model, which was established by tumor cell implantation (TCI) in the medullary cavity of the mouse femur. The BCP related behaviors were tested, including the paw withdrawal mechanical threshold (PWMT) and number of spontaneous flinches (NSF). The miRNA expression profiles in astrocytes of the sham and tumor groups were compared, and miRNA microarray and quantitative real-time PCR (qRT-PCR) assays confirmed that the amount of expression of miR-135-5p was significantly decreased in astrocytes of the tumor group. Gain- and loss-of-function studies showed that miR-135-5p could inhibit astrocytes activation and inflammation cytokines (TNF-α and IL-1β) expression. The relation between miR-135-5p and JAK2 was detected by bioinformatic analysis and dual luciferase reporter gene assay. By conducting in vitro experiments, it was shown that the miR-135-5P mimics lowered the level of JAK2/STAT3 proteins and inflammatory factors in astrocytes. Moreover, in vivo analysis on BCP mice model indicated that the miR-135-5p agonist could sufficiently increase PWMT and decrease NSF. Meanwhile, reduced activation of astrocytes in the spinal cord, as well as decreased expression of JAK2/STAT3 and inflammatory mediators, were found after miR-135-5p agonist treatment. Collectively, the results showed that miR-135-5p could potentially reduce BCP in mice through inhibiting astrocyte-mediated neuroinflammation and blocking of the JAK2/STAT3 signaling pathway, indicating that the upregulation of miR-135-5P could be a therapeutic focus in BCP treatment.

A retrospective study.To investigate the incidence, risk factors, and evolution of proximal junctional kyphosis (PJK) in young children who underwent posterior hemivertebra resection and short fusion.PJK is an undesired, but common complication following posterior spinal fusion. However, there is a paucity of data on PJK in young children after posterior hemivertebra resection and short fusion.This study included 189 children who had undergone posterior hemivertebra resection and short fusion (≤4 vertebra) from January 2008 and May 2015 at a single institution. Medical records were reviewed and radiographic assessments were made preoperatively and throughout the follow-up period. Risk factors for PJK were evaluated by correlation analysis and logistic regression analysis.The mean age at surgery was 4.5 years (range, 3-10 yr) and the average follow-up was 48.4 months (range, 24-87 mo). Twenty-two (11.6%) patients experienced PJK. PJK was identified within 6 months after surgery in 21 cases (95%), and the most common type was ligamentous failure. In comparison with the non-PJK group, the PJK group had greater preoperative segmental kyphosis (26.9° vs. 16.7°, P 0.01), longer fusion levels (3.4 vs. 2.5, P 0.01), and larger postoperative sagittal vertical axis (SVA; 18.9 vs. 8.6 mm, P 0.01). Preoperative segmental kyphosis30°(odds ratio, 4.426), and postoperative SVA of more than 20 mm (odds ratio, 3.580) were identified as independent risk factors for PJK. In PJK group, the average proximal junctional angle increased from 4.9° to 18.5° at 6 months postoperatively, but significantly decreased to 14.8° at final follow-up. Eleven patient received brace treatment, and no patients required revision surgery.Despite the incidence of PJK in 11.6% of young children undergoing posterior hemivertebra resection and short fusion, no significant deterioration of proximal junctional angle were found till the last follow-up. Its risk factors include preoperative segmental kyphosis, a larger postoperative SVA and ligamentous failure. Early detection and active management may be helpful for minimizing the progression of PJK.3.

OBJECTIVEThis study aimed to evaluate the correction results of traditional dual growing rods (DGRs) on axial rotation using CT scans and to further explore the relationships between axial and torso deformities in patients with early-onset scoliosis (EOS).METHODSPatients with EOS who were treated with traditional DGRs between January 2006 and December 2014 were retrospectively reviewed. Plain radiographs were used to assess the degree of coronal and sagittal deformity. The apical vertebral rotation (AVR) and rib hump (RH) were measured on CT scans at the apical vertebra. Pearson or Spearman rank correlation analyses were used to analyze the associations between spinal and torso deformities.RESULTSA total of 27 patients (10 boys and 17 girls, average age 6.5 ± 1.7 years) were enrolled in this study. The average number of lengthenings per patient was 5.0 ± 1.9, with a mean follow-up duration of 52.9 ± 18.2 months. The apical vertebral translation, apical vertebral body–rib ratio (AVB-R), AVR, and RH parameters were significantly decreased after the initial surgery (p < 0.05) but showed notable progression at the latest follow-up evaluation (p < 0.05). The preoperative AVR and its correction after index surgery were significantly correlated with the preoperative values as well as with the corrections of the major Cobb angle, AVB-R, and RH. During the follow-up period, significant correlations were found between the deterioration of AVR and the AVB-R and also between the deterioration of AVR and the RH from the initial surgery to the latest follow-up.CONCLUSIONSSignificant AVR correction can be achieved by DGR techniques after the initial surgery. However, this technique weakly prevents the deterioration of AVR during the follow-up period.

STUDY DESIGN A retrospective matched-cohort comparative study. OBJECTIVE The aim of this study was to compare the surgical results after the use of duet screw based satellite rods and bilateral satellite rods (S-RC) versus a standard two-rod construct (2-RC) across osteotomy sites in a matched cohort with Scheuermann kyphosis (SK). SUMMARY OF BACKGROUND DATA Multiple Ponte osteotomies are frequently employed to correct SK via a posterior-only approach, with a 2-RC across the osteotomy sites. Whereas, correction rate and junction problems remain as the major concerns. METHODS This study reviewed a consecutive series of patients with SK who had undergone posterior-only correction with multilevel Ponte osteotomy between 2009 and 2014 and had been followed over 24 months. Twenty-two patients receiving placement with an S-RC with the use of duet screws were identified and closely matched with 22 patients with a 2-RC in terms of age, apex, and magnitude of kyphosis. Comparisons were made with regards to deformity magnitude, correction results, complications, and clinical outcomes between the two groups. RESULTS No significant difference was found between groups in preoperative patient's factors (age, gender, apex, magnitude of kyphosis, and SRS-22 scores) and surgical factors (blood loss, operation time, osteotomy levels, and fused levels). Compared with the 2-RC group, the S-RC group had higher correction rate (55.4% ± 7.5% vs. 46.2% ± 5.1%, P

A retrospective study.To evaluate radiographic and cosmetic outcomes after posterior-only cervicothoracic hemivertebra resection and instrumentation.Cervicothoracic hemivertebra is a rare congenital deformity. It locates between the mobile cervical spine and the fixed thoracic spine, leading to rapid curve progression, shoulder imbalance, fixed torticollis, and facial asymmetry.This study reviewed a consecutive series of 18 patients with cervicothoracic hemivertebra. All received posterior-only hemivertebra resection and instrumentation and had a minimum follow up of 2 years. Assessments on radiographic and cosmetic outcomes were based on changes in measurements of scoliosis, shoulder balance, neck tilt, head shift, and sagittal profiles.There were 24 hemivertebrae, consisting of 16 fully segmented and 8 semisegmented. Mean age at surgery was 9.5 ± 3.1 years, and mean follow up was 32 ± 10 months. Mean fusion segments were 4.8 ± 0.6 segments. Operation time averaged 208 ± 33 minutes, with an average blood loss of 384 ± 40 mL. Local scoliosis was corrected from 39 ± 5° to 16 ± 4° (P 0.001). The distal curve had a spontaneous correction of 41 ± 18%. With regards to shoulder balance, both T1 tilt and clavicle angle were significantly improved, with a correction rate of 55 ± 22% and 47 ± 32%, respectively. Accordingly, neck tilt was improved from 20 ± 7° to 11 ± 7°, and head shift from 22 ± 9 mm to 13 ± 8 mm. A remarkable pedicle screw malpositioning rate (20%) was observed, but no neurovascular injuries. One case developed with Horner syndrome, and another one had transient radicular pain on the right arm after surgery.For patients with congenital cervicothoracic scoliosis, posterior-only hemivertebra resection with instrumentation allows for excellent scoliosis correction and cosmetic improvement. Great care should be taken to reduce the rate of pedicle screw malpositioning.4.

In most aptamer based stimulus response mesoporous silica nanoparticles (MSN) systems, the aptamer is modified on the MSN via electrostatic interaction, however leakage might exist after a certain time in the system and hence the stability is not good. In this study, the pores of MSN were capped by aptamer through click chemistry reaction for the first time and the system was then employed to develop a fluorescence biosensor. Specifically, the aptamer of the target (thrombin in this study) was hybridized with its complementary DNA (which was initially modified with alkyne at the terminal) to form a double strand DNA (dsDNA) firstly, and then this dsDNA was modified on N3 modified MSN via Cu(I) catalyzed alkyne-azide cycloaddition reaction. The guest molecules (fluorescein) were blocked in the pores of the MSN with high efficiency and nearly no leakage was detected. Upon the introduction of thrombin, thrombin specifically recognized its aptamer, so aptamer released from the MSN; and the single strand DNA(ssDNA) left could not cap the pores of the MSN efficiently and hence caused the releasing of fluorescein into the solution. The enhanced fluorescence intensity of the system has a good linear relationship with the thrombin concentration in the range of 50-1000ngmL-1 with a detection limit of 28.46ngmL-1. The proposed biosensor has been successfully applied to detect thrombin in serum samples with high selectivity. The same strategy can be applied to develop biosensors for different targets by changing the adopted aptamer.

OBJECTIVEAlthough the vertical expandable prosthetic titanium rib (VEPTR) and growing rod instrumentation (GRI) encourage spinal growth via regular lengthening, they can create different results because of their different fixation patterns and mechanisms in correcting scoliosis. Previous studies have focused comparisons on coronal plane deformity with minimal attention to the sagittal profile. In this retrospective study, the authors aimed to compare the evolution of the sagittal spinal profile in early-onset scoliosis (EOS) treated with VEPTR versus GRI.METHODSThe data for 11 patients with VEPTR and 22 with GRI were reviewed. All patients had more than 2 years’ follow-up with more than 2 lengthening procedures. Radiographic measurements were performed before and after the index surgery and at the latest follow-up. The complications in both groups were recorded.RESULTSPatients in both groups had similar diagnoses, age at the index surgery, and number of lengthening procedures. The changes in the major coronal Cobb angle and T1–S1 spinal height were not significantly different between the 2 groups. Compared with the GRI group, the VEPTR group had less correction in thoracic kyphosis (23% ± 12% vs 44% ± 16%, p < 0.001) after the index surgery and experienced a greater correction loss in thoracic kyphosis (46% ± 18% vs 11% ± 8%, p < 0.001) at the latest follow-up. Although the increase in the proximal junctional angle was not significantly different (VEPTR: 7° ± 4° vs GRI: 8° ± 5°, p = 0.569), the incidence of proximal junctional kyphosis was relatively lower in the VEPTR group (VEPTR: 18.2% vs GRI: 22.7%). No significant changes in the spinopelvic parameters were observed, while the sagittal vertical axis showed a tendency toward a neutral position in both groups. The overall complication rate was higher in the VEPTR group than in the GRI group (72.7% vs 54.5%).CONCLUSIONSThe VEPTR had coronal correction and spinal growth results similar to those with GRI. In the sagittal plane, however, the VEPTR was not comparable to the GRI in controlling thoracic kyphosis. Thus, for hyperkyphotic EOS patients, GRI is recommended over VEPTR.

The disorders of cartilage homeostasis and chondrocyte apoptosis are major events in the pathogenesis of osteoarthritis (OA). Herein, we aim to assess the chondroprotective effect and underlying mechanisms of a novel chemically modified curcumin, CMC2.24, in modulating extracellular matrix (ECM) homeostasis and inhibiting chondrocyte apoptosis. Rats underwent the anterior cruciate ligament transection, and medial menisci resection was treated by intra-articular injection with CMC2.24. In an in vitro study, rat chondrocytes were pretreated with CMC2.24 before stimulation with sodium nitroprusside (SNP). Results from in vivo studies demonstrated that the intra-articular administration of CMC2.24 ameliorated osteoarthritic cartilage destruction by promoting collagen 2a1 production and inhibited cartilage degradation and apoptosis by suppressing hypoxia-inducible factor-2a (Hif-2α), matrix metalloproteinase-3, runt-related transcription factor 2, cleaved caspase-3, and vascular endothelial growth factor and the phosphorylation of IκBα and NF-κB p65. The in vitro results revealed that CMC2.24 exhibited a strong inhibitory effect on SNP-induced chondrocyte catabolism and apoptosis. The SNP-enhanced expression of Hif-2α, a catabolic and apoptotic factor, decreased in a dose-dependent manner after CMC2.24 treatment. CMC2.24 pretreatment effectively inhibited SNP-induced IκBα and NF-κB p65 phosphorylation in rat chondrocytes, whereas pretreatment with the NF-κB antagonist BMS-345541 significantly enhanced the effects of CMC2.24. Overall, these results demonstrated that CMC2.24 attenuates OA progression by modulating ECM homeostasis and chondrocyte apoptosis by suppressing the NF-κB/Hif-2α axis, thus providing a new perspective for therapeutic strategies in OA. KEY MESSAGES: • Intra-articular injection of CMC2.24 ameliorated osteoarthritic cartilage destruction. • CMC2.24 promoted cell viability and decreased SNP-induced apoptotic gene expression. • SNP-induced activation of Hif-2α is inhibited by CMC2.24. • CMC2.24 inhibits NF-κB/Hif-2α axis activation to modulate ECM homeostasis and inhibit chondrocyte apoptosis.

The innate immune system drives inflammatory joint damage in osteoarthritis (OA) and regulates cartilage repair. Berberine chloride (BBR) is an isoquinoline alkaloid that shows immunomodulatory activity in a variety of cell lines. However, the immunomodulatory mechanisms of BBR in chondrocytes during OA are largely unknown. Herein, we assessed the ability of BBR to mediate chondroprotection through its effects on innate immunity. We found that BBR up-regulated the expression of surfactant protein D (SP-D) in OA cartilage, a key regulator of inflammation and innate immunity both in the airways and extrapulmonary tissues, including joint cartilage. To further explore these findings, we used recombinant adeno-associated virus (rAAV)-mediated knockdown of SP-D. Silencing was assessed in rat model of surgically-induced OA in the presence or absence of BBR treatment, 10 weeks post-surgery. We observed a clear improvement in histological scores of BBR-treated animals compared to those treated with BBR and the rAAV-SP-D vector. In addition, animals co-treated with BBR + recombinant human SP-D (rhSP-D) exhibited significantly lower histological scores than those treated with BBR alone. BBR treatment led to significantly reduced immune cell infiltration mediated through TLR4, F4/80, CD68 and CD34, whilst SP-D silencing reversed this improvement. In contrast, rhSP-D treatment enhanced the protective phenotype. We further explored how BBR influences SP-D and other OA-associated genes in vitro. We observed an up-regulation of SP-D and a marked decline in TRAF6, TLR4, MD-2 and MyD88 expression, as well as NF-κB p65 and IκBα phosphorylation in chondrocytes treated with sodium nitroprusside. siRNAs specific for SP-D were able to partially reverse this phenotype, whilst both rhSP-D and the TLR4 inhibitor TAK-242 enhanced the effects. Together, these results are consistent with a model wherein SP-D has therapeutic potential for OA treatment. Concomitantly, BBR modulates immune responses and decreases cartilage degradation. These findings suggest that BBR achieves this function through releasing SP-D from MD2/SP-D complexes and through the inhibition of TLR4/NF-κB signaling.

STUDY DESIGN Retrospective study. OBJECTIVE The current study aimed to evaluate the effectiveness of the hybrid growing rod (GR) technique for the treatment of young children with congenital scoliosis (CS). SUMMARY OF BACKGROUND DATA Congenital vertebral anomalies within long-spanned kyphoscoliosis were difficult to be managed by either definitive spinal fusion or standard GR technique. Hybrid technique of one-stage posterior osteotomy with short fusion and GR distraction was proposed in previous studies. There is, however, paucity of data regarding its effectiveness. METHODS Thirteen patients (mean age, 5.4 ± 2.0 yr) who had undergone hybrid GR treatment were retrospectively reviewed, including 8 patients treated with single GR and 5 patients with dual GR. All of their radiographic data were measured, and surgical complications were recorded. RESULTS On average, the current cohort had 4.1 ± 1.7 lengthening procedures. After the index surgery, the major curve improved remarkably from 86.4° ± 11.9° to 37.3° ± 12.4° (P

OBJECTIVEThis study aimed to quantify the response of the cervical spine to the surgical correction of Scheuermann’s kyphosis (SK) and to postoperative proximal junctional kyphosis (PJK).METHODSFifty-nine patients (mean age 14.6 ± 2.3 years) were enrolled in the study: 35 patients in a thoracic SK (T-SK) group and 24 in a thoracolumbar SK (TL-SK) group. The mean follow-up period was 47.2 ± 17.6 months. Radiographic data, PJK-related complications, and patient-reported outcomes were compared between groups.RESULTSThe global kyphosis significantly decreased postoperatively, and similar correction rates were observed between the two groups (mean 47.1% ± 8.6% [T-SK] vs 45.8% ± 9.4% [TL-SK], p = 0.585). The cervical lordosis (CL) in the T-SK group notably decreased from 21.4° ± 13.3° to 13.1° ± 12.4° after surgery and was maintained at 14.9° ± 10.7° at the latest follow-up, whereas in the TL-SK group, CL considerably increased from 7.2° ± 10.7° to 11.7° ± 11.1° after surgery and to 13.8° ± 8.9° at the latest follow-up. PJK was identified in 16 patients (27.1%). Its incidence in the TL-SK group was notably higher than it was in the T-SK group (41.6% [n = 10] vs 17.1% [n = 6], p = 0.037). Compared with non-PJK patients, PJK patients had greater CL and lower pain scores on the Scoliosis Research Society–22 questionnaire (p < 0.05).CONCLUSIONSHyperkyphosis correction eventually resulted in reciprocal changes in the cervical spine, with CL notably decreased in the T-SK group but significantly increased in the TL-SK group. Patients developing PJK have increased CL, which seems to have a negative effect on patients’ health-related quality of life.

Background Spinal cord injury (SCI) leads to severe motor and sensory dysfunctions. Neural stem cells (NSCs) transplantation therapy plays a positive role in functional recovery after SCI, but the effectiveness of this therapy is limited by inadequate differentiation ability of transplanted NSCs. Mammalian achaete-scute homologue-1 (Mash-1) has been reported to improve differentiation of NSCs. Thus, this study modified NSCs with Mash-1 to repair SCI. Methods NSCs isolated from rat embryo hippocampus were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-Mash-1). After establishing a SCI rat model, the rats were transplanted with Mash-1 modified NSCs, the histopathological changes of rat spinal cord were detected by hematoxylin-eosin (HE) staining, and the locomotor activity of rats was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. The NSCs cultured in vitro or extracted from SCI rat spinal cord were identified by immunofluorescence (IF). Mash-1, β3-Tubulin, and NeuN expressions in those cells were determined by Western blotting and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Results NSCs isolated from rat embryo hippocampus were Nestin- and NeuN-positive. NSC transplantation modified by Mash-1 increased BBB score of SCI rats and promoted recovery in lesion site of SCI rats. Mash-1 overexpression also promoted β3-Tubulin and NeuN expressions in NSCs cultured in vitro or extracted from spinal cord of SCI rats. Conclusion Mash-1 overexpression promoted NSC differentiation into neurons, and further improved locomotor functional recovery of SCI rats.

Previous studies have reported various predictors for curve progression in braced adolescent idiopathic scoliosis (AIS) patients. However, the reported predictors might be insufficient for patients with early AIS. The aim was to investigate whether the initial vertebra-disc ratio (VDR) could serve as an effective predictor for curve progression in early thoracic AIS (premenarchal and Risser 0) undergoing brace treatment.This study reviewed a consecutive series of early thoracic AIS girls with thoracic curve. All patients had accepted brace treatment and had regular follow-up. According to the bracing outcomes, patients were divided into two groups: Group P (progressed, curve progressed over six degrees or indicated for surgery) and Group NP (non-progressed).Totally 203 girls were included. There were 73 and 130 patients in Groups P and NP, respectively. The patients in Group P had greater initial VDR (1.9 ± 0.5 vs. 0.8 ± 0.4, P 0.01) than Group NP. During the follow-up, it showed continuous higher values in Group P than Group NP. The logistic regression analysis revealed that initial VDR had an effective value for predicting curve progression in the braced early AIS girls. The ideal cut-off point of initial VDR was 1.5 for the prediction of curve progression.The initial VDR could serve as an effective predictor for curve progression in braced early AIS girls. Evaluation of this new parameter should be carefully performed at the bracing initiation.

This study provides the discovery and validation of intervertebral disc degeneration (IDD) specific mRNA transcriptome profiles generated by NGS. We identified that insulin-like growth factor binding protein 5 (IGFBP5) was downregulated in human degenerative nucleus pulposus tissues and that its level was associated with the disc degeneration grade. In addition, the inhibitory effects of downregulated IGFBP5 are, in part, mediated through the ERK signaling pathway. Using in vivo and in vitro studies, functional characterization of the role of IGFBP5 revealed that the loss of its expression is an event in IDD pathogenesis. Therefore, strategies to maintain the expression or to prevent the repression of IGFBP5 have the potential to become a possible therapeutic and/or preventive approach for degenerative disc disease.

OBJECTIVEAs scoliosis in arthrogryposis multiplex congenita (AMC) is unusual and the number of cases reviewed in previous studies is also relatively small, no previous study exists that has directly compared the results of spinal deformity correction between AMC and adolescent idiopathic scoliosis (AIS) patients. The aim of this study was to compare the radiographic and clinical outcomes of surgical correction of spinal deformity associated with AMC versus AIS.METHODSTwenty-four adolescents with AMC were matched with 48 AIS patients in terms of Cobb angle of main curve, curve pattern, sex, age at surgery, Risser grade, and length of follow-up. Patients in both groups underwent posterior-only spinal correction and fusion procedures. The surgical outcomes and complications were analyzed and compared between the 2 groups.RESULTSIn comparison to the AIS group, the AMC group had a significantly longer mean operation time (5.6 vs 4.4 hours, p = 0.002), more blood loss (1620 ± 250 ml vs 840 ± 260 ml, p < 0.001), and more fusion levels (14.1 ± 2.3 levels vs 12.4 ± 2.5 levels, p = 0.007) as well as a lower correction rate (44.3% ± 11.1% vs 70.8% ± 12.4%, p < 0.001) and a higher rate of loss of correction (5.0% ± 3.1% vs 2.1% ± 1.9%, p < 0.001). Nine patients in the AMC group had preoperative pelvic obliquity, which was corrected from a mean of 14.2° ± 8.4° to a mean of 4.3° ± 3.2° (p < 0.001) after the surgery. The thoracic lordosis and sagittal vertical axis were significantly improved in the AMC group. Notably, however, the AMC group was found to have higher rates of screw malpositioning (15.9% vs 9.5%, p = 0.002) and complications (8/24 [33.3%] vs 4/48 [8.3%], p = 0.016) as compared to the AIS group.CONCLUSIONSCorrection of AMC-associated scoliosis tends to require a longer operating time and involve more fusion levels but results in less correction, more blood loss, and more complications, in comparison with AIS. In addition, more attention should be paid to pelvic obliquity and sagittal hyperlordosis in AMC patients.

Background Clinical and radiographic degenerative spondylolisthesis (CARDS) classification defines a distinct subset of patients with kyphotic angulation at the involved segment (type D). Research using CARDS classification to investigate motion characteristics at involved segments or patient-related outcomes (PROs) following surgical intervention is sparse. We investigated the relationship between CARDS type D spondylolisthesis and dynamic instability and PROs in type D versus non–type D spondylolisthesis. Methods We reviewed consecutive patients who received transforaminal lumbar interbody fusion for L4-5 spondylolisthesis between 2009 and 2015. Patients were assigned into type D and non–type D groups. Translational motion was determined by upright lumbar lateral radiography with supine sagittal magnetic resonance imaging or flexion and extension radiography. Demographics, radiographic parameters, and PROs were evaluated. Results Type D and non–type D groups comprised 34 and 163 patients, respectively. Compared with non–type D, type D group was characterized by lordotic angulation loss and higher degree of olisthesis on upright radiographs and demonstrated higher translational motion on upright lumbar lateral radiography with supine sagittal magnetic resonance imaging analysis. After surgery, mean reduction rate was significantly higher in type D group; type D had less slippage, but differences in slip angle and disc height were not significant. Preoperative Oswestry Disability Index and visual analog scale for back pain scores were higher in type D group. Type D spondylolisthesis and dynamic instability were associated with achieving minimal clinically important differences in PROs. Conclusions CARDS type D spondylolisthesis is a distinct subset associated with dynamic instability and worse PROs. Higher improvement in PROs can be achieved in CARDS type D spondylolisthesis after surgery.

Surface stiffness is considered a key parameter for designing high-performance implantable materials and artificial extracellular matrices because of its substantial effects on cell behavior. How to transform biomolecule recognition events, particularly chiral recognition, into stiffness change on material surfaces is biologically essential but very challenging for chemists. Here, we report a chirality-triggered stiffness transition on a smart polymer film, which consists of flexible polyethylenimine (PEI) main chains grafted with dipeptide units capable of discriminating chiral monosaccharides. The polymer film became substantially softer after interacting with L-ribose and became more rigid after interacting with D-ribose (the basic building block of DNA and RNA). This chiral effect provides a new method for determining the enantiomeric purity of an L/D-ribose mixture and facilitates the chiral separation of deoxyribose racemates as well as the separation of diverse mono-, di-, and oligosaccharides. These are three puzzle problems in carbohydrate chemistry. Furthermore, taking advantage of the significant differences in the surface stiffness, the proliferation of fibroblast cells on the polymeric surfaces can also be regulated by chiral biomolecules.

Study design This is a cross-sectional study. Objective To investigate the feasibility and safety of a novel iliosacral screw placement for sacrum-pelvis in adult pelvis by computed tomography (CT) reconstruction. Summary of background data The optimal technique of spino-pelvic fixation is still being developed and redefined. However, neither the relevant anatomic parameters nor the potential spinal canal involvement for a novel iliosacral screw placement have been clearly analyzed. Methods A total of 60 adults with normal pelvis, with the age ranging from 24 to 79 years old, were included in this study. Based on three-dimensional (3D) CT reconstruction of each pelvis, virtual iliosacral screw channel was identified bilaterally, the trajectory of which was characterized with the optimal width and length from the ilium to the sacrum. The virtual iliosacral screw channel that holding the greatest width and length of osseous channel was measured by rotating the 3D pelvis. Measurements of the determined channel on either side included iliosacral-screw-related and connector-related parameters. Results There was a virtual iliosacral screw channel passing through the ilium, the iliosacral joint and then into the sacrum on either side of each pelvis. The caudal angle, convergent angle, and maximal length were 16.3 ± 3.0°, 61.3 ± 5.9°, 97.0 ± 5.6 mm in male, respectively. In female, they were 16.4 ± 3.9°, 63.0 ± 5.5° and 96.2 ± 6.0 mm, respectively. The ideal direction of the connector was from posteromedial to anterolateral. The cephalad angle, divergent angle, and embedding depth of the connector were 28.0 ± 5.7°, 28.7 ± 5.9° and 19.0 ± 2.9 mm in male, respectively. In female, they were 26.7 ± 6.1°, 27.0 ± 5.5° and 16.4 ± 2.6 mm, respectively. Conclusion It is safe and feasible to place the iliosacral screw when performing this novel instrumentation. Preoperative CT imaging and 3D reconstructions may help to determine the correct entry point and the trajectory of iliosacral screw. Level of evidence 5.

STUDY DESIGN A retrospective study. OBJECTIVE To determine the incidence and risk factors of coronal decompensation after posterior-only thoracolumbar hemivertebra (HV) resection and short fusion in patients younger than 5-years old. SUMMARY OF BACKGROUND DATA Postoperative coronal decompensation may occur in operated patients during the follow up. However, there is a paucity of valid data regarding this complication in very young patients with thoracolumbar HV. METHODS This study reviewed a consecutive series of patients (younger than 5 years) who had undergone posterior-only hemivertebrectomy and short fusion from January 2006 to December 2014. They had a minimum follow-up of 24 months. According to the coronal compensation behavior, they were divided into two groups: Group P (progressed, curve decompensated beyond twenty degrees) and Group NP (nonprogressed, curve well compensated). RESULTS There were 179 patients included in this study. Mean age at surgery was 38 ± 11 months. Mean follow-up was 41 ± 11 months. Postoperative coronal decompensation was identified in 18 patients (rate, 10.1%) who constituted Group P. The remaining 161 patients had a well-compensated pattern. In contrast to Group NP, the patients in Group P had greater preoperative lowest instrumented vertebra (LIV) translation (18.5 mm ± 6.4 mm vs. 10.5 mm ± 4.9 mm, P

A retrospective study.To determine the incidence and risk factors of proximal junctional kyphosis (PJK) in young children who underwent posterior instrumented spinal fusion.PJK is a well-recognized postoperative complication in adults and adolescents. However, there is a paucity of valid data with regard to PJK in young children with congenital scoliosis (CS) who were treated with posterior correction surgery.This study reviewed the charts and radiographs of a consecutive series of young children with CS who underwent posterior instrumentation and fusion (≥4 levels) from January 2008 to May 2013. The patients were followed up for more than 24 months. Radiographic measurements were made preoperatively and throughout the follow-up period. From sagittal images, the following values were obtained: proximal junctional angle, sagittal vertical axis, pelvic incidence, thoracic kyphosis, lumbar lordosis, and segmental kyphosis.Totally 113 children were recruited in this study. The average age at surgery was 6.6 years, and the average follow-up period was 48.8 months. PJK occurred in 21 of the 113 patients and were mostly classified as ligamentous failure. In comparison with the non-PJK group, the PJK group showed greater preoperative Thoracic kyphosis (TK) (45.9° vs. 37.3°, P = 0.027), longer fusion levels (6.6 vs. 5.4, P 0.01), and greater segmental kyphosis (SK) change (30.1° vs. 11.2°, P = 0.002). Both a change in SK greater than 30° and a preoperative TK greater than 40° were independent risk factors associated with PJK. In the PJK group, the average PJA increased by 12.4° at 3 months postoperatively and followed by slight improvement till the final follow-up.This study demonstrates a high rate of PJK in young children after correction surgery for CS. PJK mainly occurs within 3 months postoperatively and its risk factors include preoperative hyperkyphosis, over-correction of kyphosis, and ligamentous failure.4.

BACKGROUND Growing rods (GRs) pose a higher risk of kyphosis gain while improving coronal deformity with intermittent distractions in early-onset scoliosis (EOS), but in turn, increased kyphosis may also affect GR correction outcomes. However, there is a paucity of data regarding the effect of GRs on the sagittal spinal profiles in hyperkyphotic EOS. Thus, we aim to demonstrate how hyperkyphotic EOS responds to GRs treatment. METHODS Forty patients treated with GRs for EOS were included and categorized into a normal kyphosis (N) group [20 degrees≤thoracic kyphosis (TK)≤50 degrees] or hyperkyphosis group (K) group (TK≥50 degrees). Radiographic measurements were performed before and after the index surgery and at the last follow-up. The complications were identified and classified using the surgical complications grading system. RESULTS The N group included 13 patients with dual GRs and 6 patients with a single GR. The K group consisted of 17 patients with dual GRs and 4 patients with a single GR. The mean age at surgery in the N and K groups was 6.2±1.8 and 6.4±2.1 years, respectively. The N and K groups, respectively, had an average number of lengthenings of 4.2±2.0 and 4.3±2.3, with an average follow-up of 4.7±1.9 and 4.6±2.1 years, respectively. In the K group, TK was markedly reduced after the index surgery and slightly increased during follow-up, whereas changes in TK in the N group were not significant. The complication rate in the K group was significantly higher than in the N group (81.0% vs. 47.4%, P=0.046). The most common implant-related and alignment-related complication in both groups was rod fracture (17.5%) and proximal junctional kyphosis (22.5%), respectively. The complication events in the N group were 5 with grade I and 5 with grade IIA, whereas in the K group there were 8 with grade I and 11 with grade IIA. CONCLUSIONS GRs can effectively correct hyperkyphotic EOS, with the sagittal profile being successfully restored to normal range. However, hyperkyphotic EOS tends to experience more complications such as rod fracture and PJK. LEVEL OF EVIDENCE Level III.

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS., The authors perform a genome-wide association study of adolescent idiopathic scoliosis patients of Han Chinese descent, and identify 3 new loci for disease susceptibility.

The preservation of spinal growth and prevention of pulmonary compromise in early onset scoliosis (EOS) pose particularly challenging problems for clinician and patients. Maintaining spinal and thoracic growth is critical for expansion of the thoracic cavity and the prevention of thoracic insufficiency syndrome. Nowadays, growing rod technique has been proven to be the optimal surgical treatment for this population, regardless of distraction-based or auto-growing instrumentation constructs.

Use of pedicle screws has been popularized in the treatment of pediatric spinal deformity. Despite many studies regarding the effect of pedicle screws on the immature spine, there is no study concerning the impact of addition of crosslink to pedicle-screw-based instrumentation on the development of the spinal canal in young children. This study aims to determine the influence of the screw–rod-crosslink complex on the development of the spinal canal. This study reviewed 34 patients with congenital scoliosis (14 boys and 20 girls) who were treated with posterior-only hemivertebrectomy and pedicle-screw-based short-segment instrumentation before the age of 5 years. The mean age at surgery in this cohort was 37 ± 11 months (range 21–57 months). They were followed up for at least 24 months. Of these patients, 10 underwent only pedicle screw instrumentation without crosslink, and 24 with additional crosslink placement. The vertebrae were divided into three regions as follows: (1) S-CL (screw-crosslink) region, in which the vertebrae were inserted with bilateral pedicle screws and two rods connected with the crosslink; (2) S (screw) region, in which the vertebrae were inserted with bilateral pedicle screws but without crosslink; (3) NS (no screws) region, which comprised vertebrae cephalad or caudal to the instrumented region. The area, anteroposterior and transverse diameters of the spinal canal were measured at all vertebrae on the postoperative and last follow-up computed tomography axial images. The instrumentation-related parameters were also measured, including the distance between the bilateral screws and the screw base angles. The changes in the above measurements were compared between each region to evaluate the instrumentation’s effect on the spinal canal growth. The mean follow-up was 37 ± 13 months (range 24–68 months) and the mean age at the last follow-up was 74 ± 20 months (range 46–119 months). In each region, the spinal canal dimensions significantly increased during the follow-up period. There was no significant difference in the spinal canal growth rate between the S and NS regions or between the S-CL and NS regions. Besides, a comparison of the S-CL and S regions regarding the changes in the measurements of the instrumentation construct revealed no significant differences. Pedicle-screw-based instrumentation does not cause retardation of the development of the spinal canal in young children. Moreover, use of the crosslink added to the screw–rod instrumentation also demonstrates no negative effect on the growth of the spinal canal. Thus, the addition of the crosslink to short screw-based instrumentation is recommended as an alternative to increase fixation stability in growing patients, even in very young pediatric population.

Background Only 2%-3% of patients with acute ischemic stroke receive thrombolysis. The aim of this study was to identify the reasons for exclusion from thrombolysis in patients admitted within the therapeutic time window. Methods Patient data in the hospital stroke registry between January 2012 and September 2013 were retrospectively examined. All cases with a diagnosis of ischemic stroke were screened, and those admitted to the neurology wards within 4.5 hours of symptom onset were analyzed. The reasons for exclusion from thrombolysis were examined. Logistic regression analysis was used to find independent predictors of thrombolysis treatment. Results Of the 1579 cases of ischemic stroke, 234 patients were admitted to the neurology ward within 4.5 hours of symptom onset. A total of 57 patients received thrombolysis. The thrombolysis rate was 3.6% of all ischemic stroke patients. Of the 177 patients who were excluded from thrombolysis, 36.2% (n = 64) had stroke of insufficient severity to warrant thrombolysis, and 24.9% (n = 44) were older than 80 years. Logistic regression analysis showed that the interval between symptom onset and admission (odds ratio 20.24, 95% confidence interval 3.75-109.24) and history of ischemic stroke (odds ratio .11, 95% confidence interval .04-.34) affected the likelihood of thrombolysis. Conclusions Mild stroke and advanced age were the major reasons for exclusion from thrombolysis in patients admitted within 4.5 hours of symptom onset. Patients who were admitted early and those without a history of ischemic stroke were more likely to receive thrombolysis.

Methods 20 SD patients with thoracic kyphosis aged 10 to 18 years were included in this study. 30 healthy volunteers were recruited to serve as controls. Computed tomography 3D reconstruction of the total sternum in supine position was performed. The length, width, thickness of manubrium and mesosternum was measured respectively. Meanwhile, the angle (a) between the axis of manubrium and that of mesosternum were also measured. The size of sternum and angle a were compared between SD patients and normal controls using the Studenst test.