Proximal junctional kyphosis in Lenke 5C adolescent idiopathic scoliosis after selective posterior thoracolumbar/lumbar fusion: risk factors and predictive index.

BACKGROUND: Although several studies have reported that selective posterior thoracolumbar/lumbar (TL/L) fusion can yield satisfactory results in Lenke 5C adolescent idiopathic scoliosis (AIS), the proximal junctional kyphosis (PJK) is still a common complication that occurs after surgery. The purpose of this study is to analyse the risk factors for postoperative proximal junctional kyphosis in Lenke 5C patients who underwent selective posterior TL/L fusion and explore whether PJK can be predicted. METHODS: A total of 83 AIS patients with Lenke 5C curves who met the inclusion criteria were analysed. All patients were divided into two groups based on the occurrence of postoperative PJK. Univariate and multivariate analyses were used to identify independent factors significantly associated with PJK, and an PJK index was proposed and verified. RESULTS: PJK was observed in 27 of 83 (32.5%) patients in the study. Preoperative thoracic kyphosis (TK) and the immediate postoperative proximal junctional angle (PJA) were the primary factors identified by the binary logistic regression analysis. The PJK index was defined as 1.1× preoperative TK + 2.3× immediate postoperative PJA. The receiver operating characteristics curve indicated that the occurrence rate of PJK was 85% and non-occurrence rate was 82% when the PJK index was greater than 42. CONCLUSION: Large preoperative TK and a large immediate postoperative PJA play important roles in the development of PJK in Lenke 5C patients treated with selective posterior thoracolumbar/lumbar fusion. The PJK index can be used to predict the occurrence of PJK with high accuracy. To prevent the occurrence of PJK, we should pay attention to the TLK, and preserving more posterior proximal intervertebral elements at the upper instrumented vertebral level would be an important part of corrective surgery; however, moderate correction of the lumbar curve is recommended.

Clinical survey of a pedigree with hereditary multiple exostoses and identification of EXT­2 gene deletion mutation.

The aim of the present study was to report a clinical survey of hereditary multiple exostoses (HME) in a large Chinese pedigree, and the identification of a novel deletion mutation of exostosin glycosyltransferase 2 (EXT­2) gene. A patient with multiple exostoses with huge cartilage­capped tumors in scapula, knees and ankles received surgery in Department of Orthopedics (Shanghai Changhai Hospital). A total of 20 family members were recruited to the study, with seven members (five male; two female) diagnosed as HME. The family members of the patients with HME were examined, clinical data and peripheral blood samples were collected, and their DNA was sequenced. The incidence of HME in this family pedigree was 35%. Exostoses were most frequently in the tibiae with occurrence in six patients, followed by ribs, femurs, radii, fibulae, scapulae and humeri. DNA sequencing of peripheral blood revealed a novel deletion mutation, c.824­826delGCA, in exon 5 of the EXT­2 gene, which was observed in all the patients with HME, but not in the healthy family members. Several characteristics of HME in the pedigree were observed, such as susceptibility of male gender, decreased average age of onset and height and increased severity of clinical symptoms with generations.

Click-based amplification: designed to facilitate various target labelling modes with ultralow background amplification.

We here describe a fluorescent signal amplification method termed "Click-based amplification" that can be well integrated with various click-labelling modes, including chemical labelling, genetic incorporation and covalent inhibitor probe mediated target labelling. Picolyl azide (pAz) was used as a functional group of a streptavidin-based amplifier to enhance the efficiency of click chemistry. Click-based amplification provided 3.0-12.7 fold amplification on fixed HeLa cells with different click-labelling modes. Click-based amplification has proven to be superior to tyramide signal amplification (TSA) in view of its low nonspecific amplification and high signal-to-noise ratio. Moreover, in terms of the challenging signal amplification of tissue specimens, Click-based amplification successfully achieved remarkable fluorescence enhancement on intestinal tissue slices of afatinib-N3 treated mice, which provided direct evidence of the presence of afatinib-N3 in the intestinal tissues and helped in revealing the off-target toxicity of afatinib. Collectively, these results illustrate that Click-based amplification could serve as a promising method for bioimaging studies.

Involvement of circRNA_0007059 in the regulation of postmenopausal osteoporosis by promoting the microRNA-378/BMP-2 axis.

Increasing evidence suggests that postmenopausal osteoporosis (PMO), a severe disturbance, imposes heavy physical, psychosocial, and financial burdens and dramatically influences the quality of life of postmenopausal women. Circular RNAs (circRNAs) and microRNAs (miRs) play important roles in the occurrence and development of PMO. However, the roles of circRNAs and miRs in osteoporosis regulation still need to be further investigated. circRNAs with different expression levels in patients with PMO were screened via RNA-seq and bioinformatics analysis. We found that circ_0007059 was upregulated in patients with PMO and during osteoclastogenesis of human bone marrow stromal cells (hBMSCs). Next, we investigated the effect of circ_0007059 overexpression during osteoclastogenesis of hBMSCs. circ_0007059 overexpression attenuated hBMSC differentiation into osteoclasts in vitro. This was demonstrated by downregulated bone morphogenetic protein 2 (BMP-2) expression, upregulated osteoclast-specific gene expression, and TRAP staining. circ_0007059 was demonstrated to directly target miR-378, which in turn targeted BMP-2 via bioinformatics analysis and the dual-luciferase reporter assay. Transfection of the miR-378 mimic reversed the effect of circ_0007059 on the osteoclastogenesis of hBMSCs. These results suggest that circ_0007059 plays an important role in osteoclastogenesis via the miR-378/BMP-2 signaling pathway. Targeting the circ_0007059/miR-378/BMP-2 axis is possibly a novel idea in osteoporosis treatment.

Click-ExM enables expansion microscopy for all biomolecules.

Expansion microscopy (ExM) allows super-resolution imaging on conventional fluorescence microscopes, but has been limited to proteins and nucleic acids. Here we develop click-ExM, which integrates click labeling into ExM to enable a 'one-stop-shop' method for nanoscale imaging of various types of biomolecule. By click labeling with biotin and staining with fluorescently labeled streptavidin, a large range of biomolecules can be imaged by the standard ExM procedure normally used for proteins. Using 18 clickable labels, we demonstrate click-ExM on lipids, glycans, proteins, DNA, RNA and small molecules. We demonstrate that click-ExM is applicable in cell culture systems and for tissue imaging. We further show that click-ExM is compatible with signal-amplification techniques and two-color imaging. Click-ExM thus provides a convenient and versatile method for super-resolution imaging, which may be routinely used for cell and tissue samples.

Postoperative neck tilt in Lenke 1 and 2 AIS patients after correction surgery: a novel predictive index.

BACKGROUND: Postoperative neck tilt (PNT) is a phenomenon in adolescent idiopathic scoliosis (AIS) patients which is distinct form shoulder imbalance. There were scarce studies performed to explore the risk factors for PNT in Lenke 1 and 2 AIS patients, and whether it can be predicted after surgery remains unknown. The objective of this study is to explore the prevalence and risk factors for PNT, and introduce an index for prediction of PNT in Lenke 1 and 2 AIS patients after correction surgery. METHODS: Medical records of Lenke 1 and 2 AIS patients who received correction surgery were reviewed from February 2013 to February 2015. Posteroanterior films were evaluated before surgery and at 2 years' follow-up. Patients were divided into two groups according to whether PNT occurred at the 2 years' follow-up. Risk factors of PNT were analyzed, and PNT Index was proposed and verified. RESULTS: One hundred two Lenke 1 and 2 AIS patients were recruited in this study. The prevalence of PNT after correction was 40.2%. According to the postoperative CAT (Cervical Axis Tilt), patients were divided into two group: PNT group (CAT≧5°, n = 41) and non-PNT group (CAT< 5°, n = 61). Postoperative T1 tilt, preoperative proximal thoracic curve (PTC), postoperative PTC and postoperative coronal balance (CB) were significantly different between two groups. Logistic regression showed that postoperative PTC and postoperative CB were the primary risk factors for PNT, which could be predicted by the regression equation: PNT Index = 1.1 x postoperative PTC (degrees) - 0.9 x postoperative CB (millimeters). On the basis of ROC curve, if PNT Index was more than 10, the occurrence rate of PNT was 86%. On the contrary, the rate of no PNT phenomenon was 80%. CONCLUSION: Postoperative PTC and postoperative CB were the important factors for PNT in Lenke 1 and 2 AIS patients. Sufficient correction of PTC and moderate correction of CB should be recommended when operating on Lenke1 and 2 AIS patients.

Immediate postoperative coronal imbalance in Lenke 5 and Lenke 6 adolescent idiopathic scoliosis: Is it predictable?

PURPOSE: Immediate postoperative coronal imbalance (IPCIB) is a common reason for worse postoperative appearance in adolescent idiopathic scoliosis (AIS) patients and rarely improves on its own at follow-up, thereby greatly influencing the patients' health-related quality of life. However, no studies have been performed to detect the primary risk factors for IPCIB and it remains unclear whether the condition can be predicted preoperatively. The purpose of this study is to detect the primary risk factors for IPCIB in Lenke 5 and Lenke 6 AIS patients and to explore whether IPCIB can be predicted preoperatively. METHODS: Medical records of Lenke 5 and Lenke 6 AIS patients who underwent correction surgery in our hospital from June 2017 to October 2018 were analyzed. Anteroposterior films were evaluated before and after surgery. Patients were divided into two groups, i.e., occurrence and non-occurrence of IPCIB. The risk factors for IPCIB were analyzed, and an IPCIB index was proposed and verified. RESULTS: Thirty-seven Lenke 5/Lenke 6 AIS patients with IPCIB and 48 patients without IPCIB were recruited. Univariate analysis showed that there were significant differences between the two groups in the number of unfused vertebrae, preoperative thoracic Cobb angle, preoperative lumbar Cobb angle, preoperative translation of lumbar apex, preoperative coronal balance, preoperative L5 tilt, preoperative bending L5 tilt, postoperative translation of thoracic apex, postoperative lumbar Cobb angle, postoperative translation of lumbar apex, postoperative radiographic shoulder height, and postoperative L5 tilt. Logistic regression analysis showed that the preoperative bending L5 tilt, postoperative translation of the thoracic apex, and postoperative lumbar Cobb angle were the primary risk factors for IPCIB. The IPCIB index was defined as 1.3 * preoperative bending L5 tilt + 1.5 * postoperative translation of thoracic apex - 0.8 * postoperative lumbar Cobb angle. The receiver operating characteristics curve indicated that the occurrence rate of IPCIB was 88% and the non-occurrence rate was 90% when the IPCIB index was greater than 16. CONCLUSION: The preoperative bending L5 tilt, postoperative translation of the thoracic apex, and the postoperative lumbar Cobb angle were the primary risk factors for IPCIB in Lenke 5 and Lenke 6 AIS patients. The IPCIB index can be used to predict the occurrence of IPCIB with high accuracy. Our results indicate that the thoracic curve should be adequately corrected during surgery; however, moderate correction of the lumbar curve is recommended. These slides can be retrieved under Electronic Supplementary Material.

Validation of Simplified Chinese Version of the Pain Self-Efficacy Questionnaire (SC-PSEQ) and SC-PSEQ-2 for Patients With Nonspecific Low Back Pain in Mainland China.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to develop the simplified Chinese version of Pain Self-efficacy Questionnaire (PSEQ) (SC-PESQ) and PSEQ-2 (SC-PSEQ-2), and evaluate the psychometric properties of the two questionnaires in patients with nonspecific low back pain. SUMMARY OF BACKGROUND DATA: PSEQ has been cross-culturally adapted into many languages with excellent reliability and validity. Recently, the short form of PSEQ-2 was developed and exhibited satisfactory psychometric properties. However, PSEQ and PSEQ-2 has not been translated or validated in mainland China. METHODS: The original version of PSEQ and PSEQ-2 was linguistically translated and adapted to formulate the simplified Chinese version, which was then administrated by 219 patients with low back pain, along with a set of self-report health-related instruments. Statistical analysis was performed to evaluate the psychometric properties of the SC-PESQ and SC-PSEQ-2. RESULTS: Two hundred nineteen patients with nonspecific low back pain were enlisted into the analysis. The SC-PSEQ and SC-PSEQ-2 had been determined excellent internal consistency (Cronbach alpha, 0.95 and 0.83), test-retest reliability (overall ICC, 0.91 and 0.88), and sound construct validity, which were supported by moderately strong association with the criterion measures, respectively. In addition, exploratory and confirmatory factor analysis have found and confirmed one-factor solution in SC-PSEQ as hypothesized. CONCLUSION: The SC-PESQ and SC-PSEQ-2 showed satisfactory psychometric properties in Chinese population with low back pain, and could be safely utilized to evaluating the self-efficacy in clinical and research setting. LEVEL OF EVIDENCE: 4.

Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study.

BACKGROUND: Osteosarcoma is the most common primary sarcoma of the bone. Lung osteosarcoma metastases at diagnosis have a significantly poor prognosis, even when surgery plus chemotherapy are performed. Our goal was to analyze clinical and sarcoma characteristics that could help identify factors related to an increased rate of lung metastasis and to identify different modes of treatment and its correlation with survival. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all osteosarcoma patients diagnosed from 2010 to 2015. Patient characteristics such as age, sex, ethnicity, marital status, tumor location, histologic grade, surgery, chemotherapy, radiation therapy, SEER cause-specific death classification, survival, and lung metastasis were collected. These factors were analyzed using Univariate and multivariate regression models in survival analyses. RESULTS: A total of 1057 osteosarcoma patients diagnosed from 2010 to 2015 were included, of which 176 were patients with lung metastasis. Substantial disparities in the rate of lung metastasis existed when osteosarcoma patients were stratified according to tumor location (P = 0.0002) and tumor size (P < .001). Using a Multivariate Cox regression model, being older than 30 years (vs. younger than 30, HR = 2.171, 95% CI = 1.623-2.905, P < .0001), having a tumor >5-10 cm (vs. <5 cm, HR = 2.046, 95% CI = 1.153-3.632, P = 0.0014) and >10 cm (vs. <5 cm, HR = 3.610, 95% CI = 2.066-6.310, P < .0001) were related to an increased HR for all-cause death. The HR decreased in patients with surgery (vs. no surgery, HR = 0.189, 95% CI = 0.138-0.260, P < 0.0001) and osteosarcoma. As for osteosarcoma patients with lung metastases, Multivariate Cox regressions revealed that an increased HR was associated with being older than 30 years (vs. younger than 30 years, HR = 2.142, 95% CI = 1.273-3.605, P = .0041) and married (vs. no marriage, HR = 2.418, 95% CI = 1.400-4.176, P= .0015), while a decreased HR was related to having had surgery (vs. no surgery, HR = 0.282, 95% CI = 0.171-0.464, P < .0001) and chemotherapy (vs. no chemotherapy, HR = 0.107, 95% CI = 0.050-0.229, P < .0001). CONCLUSIONS: Advanced age (older than 30 years) and large tumors were related to a higher risk of lung metastases in osteosarcoma patients. Therefore, patients who were diagnosed at advanced age or had large tumors should receive comprehensive chest CT scans. Surgery and chemotherapy can significantly improve the survival of metastatic patients, while radiotherapy did not improve survival in these patients.

Selecting the LSTV as the Lower Instrumented Vertebra in the Treatment of Lenke Types 1A and 2A Adolescent Idiopathic Scoliosis: A Minimal 3-year Follow-up.

STUDY DESIGN: Retrospective study. OBJECTIVE: The purpose of this study was to verify the last substantially touched vertebra (LSTV) as the ideal lower instrumented vertebra (LIV) and to identify predictive factors of adding-on in patients with Lenke type 1A and 2A curve patterns when LSTV was chosen as the LIV. SUMMARY OF BACKGROUND DATA: Although several studies have indicated that the use of the LSTV as the LIV can obtain favorable outcomes in Lenke 1A and 2A curves, the factors identifying patients with Lenke 1A and 2A curve patterns who should undergo a fusion extending beyond the LSTV have not been identified. METHODS: A total of 120 patients with Lenke 1 and 2 curves after posterior instrumentation and fusion to the LSTV were evaluated. All patients had a minimum 3-year follow-up. Patients were grouped based on the occurrence of the distal adding-on phenomenon: an adding-on group and a no adding-on group. We analyzed the significant independent factors associated with adding-on via univariate analysis and then via stepwise logistic regression analysis. RESULTS: Distal adding-on was observed in 16 patients (13.33%). Binary logistic regression analysis showed that the Risser sign (OR = 0.592, P = 0.033), preoperative distance between the LIV and the center sacral vertical line (CSVL) (LIV-CSVL) (OR = 1.286, P = 0.002), and postoperative thoracic kyphosis (T5-T12) (OR = 0.784, P = 0.002) were primary factors for distal adding-on. CONCLUSION: Selecting the LSTV as the LIV simplifies the selection of the LIV and is an effective operation strategy in patients with Lenke 1A and 2A curve types. Patients with lower Risser sign, larger preoperative LIV-CSVL, and postoperative thoracic hypokyphosis are more likely to develop distal adding-on at 3-year follow-up. LEVEL OF EVIDENCE: 4.

Syntheses of [1,2,4]triazolo[1,5-a]benzazoles enabled by the transition-metal-free oxidative N-N bond formation.

A transition-metal-free oxidative N-N bond formation strategy was developed to generate various structurally interesting [1,2,4]triazolo[1,5-a]benzazoles efficiently. The mechanism of the key oxidative N-N bond formation was investigated by using an intramolecular competition reaction. Notably, the first single crystal structure was also obtained to confirm the structure of 2-aryl[1,2,4]triazolo[1,5-a]benzimidazole.

Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome.

Pseudouridine (Ψ) is the most abundant post-transcriptional RNA modification, yet little is known about its prevalence, mechanism and function in mRNA. Here, we performed quantitative MS analysis and show that Ψ is much more prevalent (Ψ/U ratio ∼0.2-0.6%) in mammalian mRNA than previously believed. We developed N3-CMC-enriched pseudouridine sequencing (CeU-Seq), a selective chemical labeling and pulldown method, to identify 2,084 Ψ sites within 1,929 human transcripts, of which four (in ribosomal RNA and EEF1A1 mRNA) are biochemically verified. We show that hPUS1, a known Ψ synthase, acts on human mRNA; under stress, CeU-Seq demonstrates inducible and stress-specific mRNA pseudouridylation. Applying CeU-Seq to the mouse transcriptome revealed conserved and tissue-specific pseudouridylation. Collectively, our approaches allow comprehensive analysis of transcriptome-wide pseudouridylation and provide tools for functional studies of Ψ-mediated epigenetic regulation.

Synthesis of high-quality water-soluble near-infrared-emitting CdTe quantum dots capped with 3-mercaptobutyric acid.

Highly fluorescent CdTe quantum dots (QDs) with emission in red to near-infrared (NIR) wavelength were successfully prepared by using 3-mercaptobutyric acid (3MBA) as capping agent. The maximum of quantum yield (QY) could reach up to 82% for QDs with emission peak at 686 nm and FWHM of 66 nm at optimal conditions. The QY of these QDs could maintain above 65% in the 650-750 nm region and QDs with emission over 800 nm were still strong fluorescent (28-41%). These optical properties of CdTe quantum dots are among the best results prepared by the state-of-the-art methods, suggesting their promising applications in bio-imaging. The success of 3MBA as excellent capping agent in this method was attributed to the balanced chain length and methyl side chain in comparison to a series of linear and branched mercapto acids, namely thioglycolic acid, thiolactic acid, 3-mercaptopropionic acid, 4-mercaptobutyric acid, 5-mercaptovaleric acid, 4-mercaptovaleric acid and 3-mercapto-2-methylbutyric acid.