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VBT is a novel alternative to spinal fusion surgery to treat skeletally immature AIS and was approved to correct idiopathic scoliosis in August 2019 by US Federal Drug Administration (FDA). To systemically review the preliminary outcomes of vertebral body tethering (VBT) in treating adolescent idiopathic scoliosis.The electronic databases PubMed, EMBASE, and Web of Science were queried up to January 2022 for articles regarding VBT. Basic characteristics of patients, changes of radiographic parameters in coronal and sagittal planes, and clinical outcomes of surgical treatment of VBT including complication and revision rates were summarized.Twenty five studies met the inclusion criteria. Most studies (23/25) included patients with only skeletal immaturity. The average % correction of the main/tethered curve at final follow-up, and % correction of thoracic kyphosis at final follow-up were reported to be 15.6-106.5% and - 31.8 to 20.0%, respectively. The most common complications for VBT were tether breakage (n = 145;21.3%), pulmonary complications (n = 49; 6.9%), and overcorrection (n = 30; 4.2%). The revision rate was 13.1%.VBT could effectively and safely correct spinal deformity in skeletally immature patients with AIS and preserve the motion and growth of the spine. However, VBT has a relatively high complication and revision rates. Therefore, surgeons should cautiously consider VBT for treating AIS. Future research efforts are needed to lower the complication and revision rates. Whatever, VBT is still in its infancy and may have a promising future as a non-fusion solution for AIS.

Innovative therapeutic strategies are urgently needed for Alzheimer’s disease (AD) due to the increasing size of the aging population and the lack of effective drug treatment. Here, we report the therapeutic effects of extracellular vesicles (EVs) secreted by microglia, including macrosomes and small EVs, on AD-associated pathology. Macrosomes strongly inhibited β-amyloid (Aβ) aggregation and rescued cells from Aβ misfolding–induced cytotoxicity. Furthermore, macrosome administration reduced Aβ plaques and ameliorated cognitive impairment in mice with AD. In contrast, small EVs slightly promoted Aβ aggregation and did not improve AD pathology. Proteomic analysis of small EVs and macrosomes revealed that macrosomes harbor several important neuroprotective proteins that inhibit Aβ misfolding. In particular, the small integral membrane protein 10–like protein 2B in macrosomes has been shown to inhibit Aβ aggregation. Our observations provide an alternative therapeutic strategy for the treatment of AD over conventional ineffective drug treatments.

N4-acetylcytidine (ac4C) is an epitranscriptomic modification of mRNA that is catalyzed by N-acetyltransferase 10 (NAT10), a critical factor known to influence mRNA stability. However, its role in development has not been investigated. In this study, we used CRISPR/Cas9 and RNAi technology to knock out and knock down nat10, the zebrafish ortholog of human NAT10, and evaluated their effects on development, behavior, and transcriptome. Our findings indicate that nat10 deficiency in zebrafish embryos results in increased embryo mortality and developmental abnormalities. Additionally, behavioral and histological evaluations revealed that nat10 knockdown led to increased anxiety-like behavior and severe vision impairment. Transcriptome profiling and RT-PCR results showed that nat10 knockdown significantly downregulated the expression of retinal transcripts that are enriched in response to light stimuli, photoreceptors, and visual perception. Furthermore, dot-blot and RIP-PCR analyses confirmed a significant reduction in ac4C levels in total RNA and opsin mRNA in nat10 knockdown zebrafish. Our results highlight the essential role of ac4C in embryonic development, especially in visual development. This zebrafish model could be helpful for studying ac4C modification in neurodevelopmental disorders.

We used NHANES data to explore the association between dietary quality estimated by the HEI-2015 and osteoporosis in middle-aged and elderly US adults. We found that higher dietary quality is significantly associated with a reduced risk of osteoporosis among middle-aged and elderly Americans. Introduction Through this research, we assess whether increasing the overall dietary quality reduces the risk of osteoporosis. Methods For our analyses, we combined data collected from four NHANES 2-year cycles (2007-2008, 2009-2010, 2013-2014, and 2017-2018), including 10,033 participants. Associations between osteoporosis and HEI-2015 total/component scores among middle-aged and elderly adults were examined using logistic regression models. Osteoporosis was defined as femur neck BMD values equal to or less than 2.5 standard deviations (SDs) below the mean of the young adult reference group, and dietary intake data were obtained from two NHANES 24-h recall interviews. Results After multivariable adjustment, middle-aged and elderly populations with quintile 4 (OR: 0.54, 95% CI 0.34, 0.84; P = 0.007) and quintile 5 HEI-2015 total scores (OR: 0.43, 95% CI 0.26, 0.70; P = 0.001) were associated with reduced odds of osteoporosis compared with quintile 1. Higher intake of total vegetables, greens and beans, total fruits, whole fruits, and whole grains was associated with decreased odds of osteoporosis among elderly adults. Surprisingly, saturated fat intake can also protect against osteoporosis. Conclusion Higher dietary quality estimated from HEI-2015 total and component food scores was significantly associated with a reduced risk of osteoporosis among the middle-aged and elderly Americans participating in NHANES included in this study.

Background. Up to now, an accurate nomogram to predict the lung metastasis probability in Ewing sarcoma (ES) at initial diagnosis is lacking. Our objective was to construct and validate a nomogram for the prediction of lung metastasis in ES patients. Methods. A total of 1157 patients with ES from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. The predictors of lung metastasis were identified via the least absolute shrinkage and selection operator (LASSO) and multivariate logistic analysis. The discrimination and calibration of the nomogram were validated by receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was used to evaluate the clinical usefulness and net benefits of the prediction model. Results. Factors including age, tumor size, primary site, tumor extension, and other site metastasis were identified as the ultimate predictors for the nomogram. The calibration curves for the training and validation cohorts both revealed good agreement, and the Hosmer&ndash, Lemeshow test identified that the model was well fitted (p &gt, 0.05). In addition, the area under the ROC curve (AUC) values in the training and validation cohorts were 0.732 (95% confidence interval, CI: 0.607&ndash, 0.808) and 0.741 (95% CI: 0.602&ndash, 0.856), respectively, indicating good predictive discrimination. The DCA showed that when the predictive metastasis probability was between 1% and 90%, the nomogram could provide clinical usefulness and net benefit. Conclusion. The nomogram constructed and validated by us could provide a convenient and effective tool for clinicians that can improve prediction of the probability of lung metastasis in patients with ES at initial diagnosis.

In the present investigation, the growth kinetics of interfacial reaction layer products between cubic boron nitride (CBN) and Cu-Sn-Ti filler metal has been thoroughly investigated. Detailed morphological and compositional features of respective compounds have been demonstrated for a wide brazing temperature ranging from 1153 K to 1223 K. It is found that within 30 minutes brazing holding time, the reaction layer growth is largely determined by the population of TiN via effective Ti diffusion with an activation energy of 223.51 kJ/mol, leading to parabolic growth patterns. It is further revealed that TiN grows both in axial and length dimensions, which eventually extends to the forefront and covers the reaction layer.

Some studies have suggested an association between serum copper and bone density. Few studies have explored the association between copper intake and osteoporosis and bone mineral density (BMD). Our research aims to assess the associations of copper intake with the risk of osteoporosis in United States adults using the National Health and Nutritional Examination Surveys (NHANES). A total of 8224 individuals were included in our study. Osteoporosis was defined that BMD values surpass 2.5 standard deviations (SD) below the mean of the young adult reference group. Copper intake from diets and supplements was estimated by using two 24-h recall surveys. After adjustment for all the covariates of interest, the odds ratios (ORs) (95% confidence interval (CI)) between the risk of osteoporosis and total copper intake across quartiles 3 and 4 compared with quartile 1 were 0.48 (0.31–0.74) (P

Mounting clinical evidence has revealed that the vitamin D receptor (VDR) is associated with cholestatic liver injury, although the functions of VDR in this condition remain largely unexplored. Here, we investigated the effects of VDR activation on bile duct ligation (BDL) mice, and the underlying mechanisms were further investigated. A low-calcemic VDR agonist, paricalcitol (PAL, 200 ng/kg), was intraperitoneally injected into BDL mice every other day for 5 days or 28 days. Liver histology, liver function indicators, cholangiocyte proliferation, fibrosis scores, and inflammation were evaluated. Mice treated with PAL were rescued from the decreased survival rate induced by BDL and liver damage was reduced. Mechanistically, PAL promoted cholangiocyte proliferation, which was likely conducive to proliferating bile duct maturation and increased branching of bile ducts. PAL treatment also increased the expression of Yes-associated protein (YAP) and its target protein epithelial cell adhesion molecule (EpCam) and decreased the level of inactive cytoplasmic phosphorylated YAP. YAP knockdown abrogated PAL-induced primary bile duct epithelial cell proliferation, confirmed with YAP inhibitor administration. In addition, BDL-induced liver fibrosis and inflammatory cell infiltration were reduced by PAL treatment at both day 5 and day 28 post-BDL. In conclusion, VDR activation mitigates cholestatic liver injury by promoting adaptive bile duct remodeling through cholangiocytic YAP upregulation. Because PAL is an approved clinical drug, it may be useful for treatment of cholestatic liver disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

In the present study, we offer an in-depth analysis over the microstructure, thickness and product composition of the interfacial reaction layer generated upon CBN/Cu-Sn-Ti active filler metal at 1223 K. Current findings demonstrate that adequate wettability and satisfactory bonding have been achieved via chemical reactions between Ti and N, B. More importantly, we report, for the first time, the formation of a three-layer juxtaposition of reaction products, namely, TiN, TiB2 and TiB, along the diffusion path of Ti. Meanwhile, we determine the average layer thickness to be 1.24 μm. Through deep etching, we unambiguously present morphologies of the newly formed TiN and TiB2, which are columnar and bulky, respectively, and constitute the formation of a high strength metallurgical interfacial bonding layer, and is crucial towards gaining enhanced grinding performance. Finally, we propose a possible reaction sequence and mechanism that govern the nucleation and growth of corresponding crystals.

Background Cases of obturator nerve impingement (ONI) caused by osteophytes resulting from bone hyperplasia on the sacroiliac articular surface have never been reported. This paper presents such a case in a patient in whom severe lower limb pain was caused by osteophyte compression of the sacroiliac joint on the obturator nerve. Case summary A 65-year-old Asian man presented with severe pain and numbness in his left lower limb, which became aggravated during walking and showed intermittent claudication. The physical examination revealed that the muscle strength of the left lower limb had decreased and that the passive knee flexion test result was positive. Computed tomography (CT) and 3D reconstruction showed a large osteophyte located in the anterior lower part of the left sacroiliac joint. The results of electrophysiological examination showed peripheral neuropathy. A CT-guided obturator nerve block significantly reduced the severity of pain in this patient. According to the above findings, ONI caused by the osteophyte in the sacroiliac joint was diagnosed. This patient underwent an operation to remove the bone spur and symptomatic treatment. After therapy, the patient's pain and numbness were significantly relieved. The last follow-up was performed 6 mo after the operation, and the patient recovered well without other complications, returned to work, and resumed his normal lifestyle. Conclusion Osteophytes of the sacroiliac joint can cause ONI, which leads to symptoms including severe radiative pain in the lower limb in patients. The diagnosis and differentiation of this disease should attract the attention of clinicians. Surgical excision of osteophytes should be considered when conservative treatment is not effective.

Colorectal carcinoma is a complex disease accounting for adenoma tumors and an aggressive phenotype, and the third leading cause of cancer death. In the past decades, miRNAs have been associated with molecular pathways of cancer and other diseases. The dysregulated miRNAs play an inhibitory or promoting role in tumorigenesis. Therefore, restoration of tumor-suppressed microRNAs (miRNA) may offer novel therapeutic approaches for cancer treatment. Nevertheless, the poor bioavailability of miRNA due to their rapid enzymatic degradation is a critical barrier in cancer gene therapy. To overcome this dilemma, we designed disulfide cross-linking micelles (DCM) nanocarrier for delivery of miR-145 to colon cancer cells and investigated its therapeutic efficacy in vitro and in vivo. Results indicated that the presence of DCM nanocarrier loaded with miR-145 enhanced selective delivery of miR-145 and facilitated cellular uptake, significantly up-regulating miR-145 expression in HCT-116 cell lines. Consequently, the cell proliferation was inhibited by arresting cell cycle at the G1 phase. Further, apoptosis of HCT-116 cells treated with miR-145 complex nanoparticles may be via downregulation of oncogenes MYC and FSCN1, predicting regulatory targets for miR-145. These results pave the way for further investigations into the potential of miR-145 complex nanocarrier for cancer gene therapy.

Effects of different holding time on CBN/Cu-Sn-Ti composites have been thoroughly documented. It is revealed that adequate wetting can only take place at 30 minutes and beyond. The thickness of reaction layer is governed by Ti diffusion, and follows a parabolic growth rate until Ti is fully consumed at the compensation of interfacial reactions. Concurrently, more stable Cu3Sn1 has been generated due to the decomposition of unstable Cu41Sn11, which leads to an enhanced wear performance.

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The objective of this study was to investigate the effects of co-exposure of iron and microplastics (MPs) on the cognitive function of aged humans and animals. It was already known that individual iron or MPs exposure can initiate potential neurotoxicity. However, the combined effect of MPs and iron remained to be elucidated. In this study, the toxicity of iron, MPs, co-treatment of MPsiron, and the underlying mechanisms were evaluated in vivo. Our findings suggest that 5 µm MPs could enter the aging mice brain and accumulate in cortex and hippocampus. In addition, MPs and iron have a good binding ability, therefore, co-exposure of MPsiron cause significant iron overload and cognitive deficits as compared to control and individual treatments of iron and MPs. Moreover, the lipid peroxidation and inflammation, which are involved in ferroptosis, get significantly elevated by co-exposure of iron and MPs. Taken together, our results provide compelling evidence that co-exposure of iron and MPs could aggravate the cognitive impairment via disturbing brain iron homeostasis and inducing ferroptosis in cognitive-related brain areas, what's more, the results warn that MPs may act as vectors of pollutants (mostly heavy metals) increasing the health burden on body.

STUDY DESIGN Retrospective analysis. OBJECTIVE The aim of this study was to develop and validate a nomogram for the prediction of lung metastasis in patients with malignant primary spinal tumors. SUMMARY OF BACKGROUND DATA In patients with malignant primary spinal tumors, lung metastasis is usually found by computed tomography (CT) and is considered to be an essential factor affecting the prognosis and survival. METHODS We retrospectively collected 580 malignant primary osseous spinal neoplasms patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic analysis were used to identify independent factors. These prognostic factors were included in the nomograms. The nomograms were validated based on its calibration, discrimination, and clinical utility. The overall survival of the patients was analyzed using the Kaplan-Meier method and the survival differences were tested by the log-rank test. RESULTS We randomly divided all these patients (n = 580) into a training cohort (n = 408) and a validation cohort (n = 172). The results showed that the risk of lung metastasis was independently influenced by histologic type, use of surgery, clinical T stage, clinical N stage, and tumor extension (all P

Objective To perform a meta-analysis exploring the correlation between cervical lordosis (CL) and sagittal spine alignment in patients with adolescent idiopathic scoliosis (AIS) after surgery for determining a surgical strategy. Methods We searched 3 electronic databases for studies discussing the correlation between CL and spine sagittal alignment in patients with AIS. Studies reported from the inception of the database to June 2019 were retrieved without any language restrictions. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. In addition, we conducted subgroup analyses in different curve type subgroups with at least 2 studies. Results Ten relevant studies involving 539 patients were evaluated in this meta-analysis. The Pearson correlation (r) for CL and the T1 slope was –0.69; (95% CI, –0.79 to –0.54). The fixed-effects summary correlation between CL and thoracic kyphosis in patients was moderate (r = –0.40; 95% CI, –0.48 to –0.31). In addition, the fixed-effects summary correlations between CL and lumbar lordosis (r = 0.19; 95% CI, 0.07–0.30), pelvic incidence (r = –0.08; 95% CI, –0.20 to 0.04), pelvic tilt (r = –0.06; 95% CI, –0.18 to 0.06), and sacral slope (r = –0.06; 95% CI, –0.18 to 0.06) in patients were weak. Conclusions There is a strong negative correlation between CL and the T1 slope in patients with AIS. Given the lack of robust clinical evidence, these findings warrant verification by large prospective registries and randomized trials with long follow-up periods.

Background Long non-coding RNAs are important regulators in cancer cell tumorigenesis. We have demonstrated in a prior study that lncRNA FTX is dysregulated in gastric cancer (GC). In this study, we aim to report gastric cancer-related lncRNA FTX as a main regulator in GC development and progression. Methods In vitro and in vivo assays of FTX alterations have been performed to reveal a complex integrated phenotype affecting cell growth, migration, and invasion. lncRNA FTX expression levels in gastric cancer cells and normal cells were measured by RT-PCR. Luciferase reporter assays, Western blotting, and many immune, microscopy technologies were utilized to investigate the expressions of FTX- related proteins and RNAs. The functional role of FTX in cell growth, migration, and invasion were observed in vitro and in vivo. Results We explored the underlying mechanisms of FTX in GC development, and the microRNAs' relationship with FTX. We found that FTX promoted cell proliferation, migration, and invasion, as well as tumor growth, and this effect could latterly be attenuated by miR-144. ZFX attenuated the effects of FTX/miR-144 axis by sponging with miR-144. Conclusion In summary, the above results support a model in which the FTX/miR-144/ZFX act as important effectors in GC tumorigenesis and progression, indicating new therapeutic methods in GC.

Cubic boron nitride (CBN)/Cu-Sn-Ti composites as potential superabrasive products are prepared. It is found that as the temperature increases, porosity keeps decreasing from 1123 K to 1223 K but becomes virtually constant afterward, which is inversely coupled to the reaction layer thickness variation. Weight loss arrives at the minimum value at 1223 K. Deep etching over the interfacial region reveals that TiN and TiB2 compounds have been generated, and their roles in determining wear properties are postulated.

The aim of this study was to construct and validate nomograms for predicting lung metastasis and lung metastasis subgroup overall survival in malignant primary osseous neoplasms. Least absolute shrinkage and selection operator, logistic and Cox analyses were used to identify risk factors for lung metastasis in malignant primary osseous neoplasms and prognostic factors for overall survival in the lung metastasis subgroup. Further, nomograms were established and validated. A total of 3184 patients were collected. Variables including age, histology type, American Joint Committee on Cancer T and N stage, other site metastasis, tumor extension and surgery were extracted for the nomograms. The authors found that nomograms could provide an effective approach for clinicians to identify patients with a high risk of lung metastasis in malignant primary osseous neoplasms and perform a personalized overall survival evaluation for the lung metastasis subgroup.

Cubic boron nitride (CBN) grains are brazed by Cu-Sn-Ti filler metal in vacuum at 1223 K. Wetting behaviors, reaction layer features, and elemental distribution characteristics have been systematically investigated through scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). The results show that when the TiH2 content is 5 wt pct, virtually no sharp-edged, partially coated, and uncoated CBN grains can be observed, indicating that adequate wetting could be achieved. Moreover, a continuous reaction layer with uniform thickness (1.30 μm) consisting of TiN, TiB2, and TiB is obtained, which indicates that large numbers of TiN, TiB2, and TiB compounds could have been formed at the interface. However, when the TiH2 content exceeds 5 wt pct, the thickness of the reaction layer is no longer significantly expanding and excessive Ti present in the matrix will lower the volume percentage of Cu3Sn1 phase, which will reduce the bonding strength of the brazing samples. Wear tests indicate that the minimum weight loss also occurs at 5 wt pct TiH2.

Superior mesenteric artery (SMA) syndrome is a well-recognized, rare complication of undergoing surgical correction of a spinal deformity. The objective of this study was to summarize the best available evidence on SMA syndrome treatment after scoliosis surgery. To identify differences, special attention was paid to scoliosis pathology, intervention and SMA syndrome presentation.A systematic review of the literature was performed on SMA syndrome following scoliosis surgery. The Web of Science, PubMed, Wanfang (Chinese) and EMBASE databases were systematically searched for articles from January 1971 to October 2020. The main subjects discussed are scoliosis pathology, intervention and SMA syndrome presentation.A total of 32 articles with 52 cases were included in our report. The mean age of patients with SMA syndrome following scoliosis surgery was 14.7 ± 2.9 years and the majority (n = 42, 80.8%) were girls. The most frequently reported scoliosis type was adolescent idiopathic scoliosis (n = 34, 65.4%). The mean postoperative days (POD) (interval between the surgical treatment and the onset of symptoms) was 9.6 ± 9.5 days. Different treatment methods were analyzed in 46 patients. We noted a trend toward a higher percentage of patients with POD48 hr in the group with surgical treatment than in the conservative treatment group (P = 0.002).In summary, in this systematic review, for the first time, we found that the time of onset of postoperative symptoms can be used as an important reference index for surgical intervention. We also believe that recommendations about the treatment of SMA syndrome following scoliosis surgery should include this finding. Given the lack of robust clinical evidence, these findings warrant verification in a prospective multicenter screening trial.

Nanocarriers with integrated advantage, such as excellent stealth property, active targeting function, and rapid intracellular drug release, are significant for cancer treatment. Herein, a biodegradable zwitterionic triblock copolymer containing disulfide-linked poly-ε-caprolactone and polycarboxybetaine methacrylate (PCB-SS-PCL-SS-PCB) was first synthesized and then partly modified with galactosamine (GAL) for constructing polymeric micelle drug carrier with multifunctionality. Polymeric micelles showed ultralow protein absorption in serum and obvious reduction-responsiveness in the presence of glutathione, provided by the zwitterionic polymer shell and the disulfide bond, respectively. Furthermore, active targeting of the carrier to hepatic carcinoma cells was achieved via GAL ligands on PCB shells due to their specific binding to asialoglycoprotein receptors on the cell surface. As expected, in vivo competition studies demonstrated that doxorubicin- (DOX-) loaded GAL-modified micelles have better anticancer effect in hepatic tumor-bearing mice than free DOX and nontargetable micelles. As a result, this novel multifunctional carrier provides a valuable strategy to design promising anticancer drug delivery systems for liver cancer treatment.

Some studies have reported that the electromagnetic navigation (EN) technique is better than the free-hand (FH) method. Nevertheless, there are few clinical trials. In recent years, several clinical trials have been conducted, providing sufficient information to compare the two methods. We compared the FH and EN techniques (SURESHOT, Smith and Nephew, Inc., Memphis, TN) in terms of the distal locking time, exposure time, first success rate, healing time and operative time. We comprehensively searched the Medline, Embase, and Cochrane library databases according to predetermined inclusion and exclusion criteria, and then we extracted data for specific variables from these reports. The risk of bias was assessed. Stata 13.0 was used for analysis. Nine studies involving 579 patients were pooled in this study. The meta-analysis showed that EN was associated with a shorter distal locking time (P = 0.001) and exposure time (P = 0.001) than FH performed by surgeons who are not proficient in using the FH technique. No significant differences were found in the first success rate (P = 0.231), healing time (P = 0.09) or operative time (P = 0.510). The EN technique has the advantages of a shorter distal locking time and smaller amount of ionizing radiation exposure compared with the FH technique.

Background: There are several risk factors for proximal junctional kyphosis (PJK) in adolescent idiopathic scoliosis (AIS) surgery. Decreased rod contouring angle (RCA) has been proposed as a risk factor for PJK, but the role of difference between proximal junctional angle (PJA) and RCA (PJA-RCA) has not been fully investigated. The aim of this study was to assess the role of PJA-RCA for the development of postoperative PJK in AIS. Methods: We performed a retrospective analysis of 96 AIS patients who underwent posterior segmental spinal instrumentation and fusion between the years 2012 and 2018 (minimum 1.5-year and average 2-year follow-up) at a single institution. Each patient was measured on preoperative, postoperative and final follow-up long-cassette standing radiographs. The PJA-RCA was regarded as a new definition that reflects the match degree between proximal rod contouring and vertebra curvature, and radiographic parameters were compared between PJK and non-PJK group. Results : Among the 96 patients with a mean age of 14.00 years (± 0.82), the overall incidence of PJK was 22%. PJK group showed a significantly greater preoperative SVA (P = 0.032) and larger correction of SVA (P = 0.007) than non-PJK group. At the last follow-up, PJK patients had significantly greater LL (P = 0.046). Patients in the PJK group had significantly greater preoperative PJA-RCA than the non-PJK group (4.07±3.30 vs. 1.42±4.28, P = 0.024). However, RCA was not significantly different between two groups (3.88 ± 4.34 vs. 2.86 ± 3.36, P = 0.405). In addition, Pearson correlation coefficient showed a significant correlation between the change of SVA and the last follow-up PJA (r = -0.208, P = 0.042). Preoperative PJA-RCA and postoperative PJA-RCA demonstrated similar results which showed a strong correlation with the last follow-up PJA (r = 0.528 and r = 0.532 respectively, P < 0.000). Conclusions: As a new reflex of improper rod contouring, large PJA-RCA is a risk factor for PJK in AIS, and PJK might be a compensation mechanism rather than complication when spine is shifted and overcorrected. Keywords: adolescent idiopathic scoliosis, proximal junctional kyphosis, proximal junctional angle, rod contouring angle.

Aim Osteoarthritis (OA) is the most common joint disorder and a leading cause of disability. While early proactive management is crucial in alleviating symptoms in OA patients, currently available therapeutic approaches are yet to achieve an ideal level of efficacy. The path to the development of a potent treatment begins with the thorough understanding of the pathophysiology of OA. The present study aims to explore the mechanism by which SGK1 is involved in OA progression. Methods Firstly, the potential target gene of SGK1 was screened and SGK1 expression was determined in OA through bioinformatics analysis. Mouse OA model was then established and chondrocytes were extracted, after which inflammation was induced with lipopolysaccharide (LPS). Following LPS treatment, the chondrocytes were transfected with synthesized plasmids to explore the impact of SGK1, CREB1, and ABCA1 on apoptosis, proliferation and inflammation in OA. ChIP-PCR and dual-luciferase reporter gene assay were conducted to determine the binding relation between SGK1 and CREB1 as well as between CREB1 and ABCA1. Results OA mice presented with high expression of SGK1. Interestingly, we found that SGK1 inhibited CREB1 expression in chondrocytes, thereby inducing inflammation and suppressing chondrocyte proliferation. CREB1 was found to have a positive correlation with ABCA1 expression, while down-regulation of CREB1 resulted in the inhibition of cell proliferation and aggravated inflammation, which could be reversed by overexpressed ABCA1. Conclusion Taken altogether, silencing of SGK1 alleviated OA through epigenetic regulation of CREB1 and ABCA1 expression. These findings may provide novel insight into SGK1-based strategy for OA treatment.

The successful launch of the Chinese Beidou (Compass) Navigation Satellite System (hereafter refers to as BDS) makes it the third operational navigation satellite system capable of offering regional services after GPS and GLONASS in the end of 2012. Yet considering the dominant role of GPS in global GNSS market, it's a great challenge to maximize the utilization of other systems and cultivate competitive domestic navigation industries for all latecomers in the GNSS community. This paper analyzes the current strategy of BDS industrialization by a detailed review of current policy documents from both central and local government, examines the progress of BDS industrialization based on statistical data and expert interviews, and summarized the current strategy of BDS industrialization as indigenous in key domains and compatible in commercialization. Then a stakeholder analysis is conducted to analyze the consideration behind current strategy. This paper also comes up with several policy recommendations for Chinese decision makers' reference to improve BDS related policies in the future from a latecomer's perspective based on detailed comparison analysis of BDS's advantages and disadvantages.

Inflammatory bowel disease (IBD) is a risk factor in colon cancer. Endoplasmic reticulum (ER) stress is associated with IBD and cancer. In the current study an azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced mouse colonic tumor model was established to analyze the expression of ER stress chaperone molecules. Female C57BL/6 mice were intraperitoneally injected with 12 mg/kg AOM. On the 7th day following AOM injection, mice were treated with 1% DSS supplemented to the drinking water for 7 days, then followed by 14 days of normal drinking water. The cycle of 7 days DSS plus 14 days normal water was repeated twice and colonic tumors were evaluated for their number and size. Mice in the control group were injected with saline and received normal drinking water for the course of the experiment. mRNA levels of cytokines, inositol-requiring enzyme (IRE)1α and 1β, their downstream targets X-box binding protein (XBP)1u, XBP1s and mucin (MUC) 2 and interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α were detected by reverse transcription-quantitative polymerase chain reaction. IRE1α, IRE1β and MUC2 protein expression was evaluated by immunohistochemistry, and IRE1α and IRE1β levels were further assessed by western blot analysis. It was observed that tumors developed in the distal colon of mice treated with AOM/DSS. IL-6, IL-8 and TNF-α mRNA levels were significantly increased in mice of the tumor group compared with mice of the control group. There were no significant differences in IRE1α mRNA and protein expression between the two groups and XBP1s mRNA levels were increased in the tumor compared with the control group. IRE1β and MUC2 mRNA levels were significantly decreased in the tumor compared with the control group (decreased by 42 and 30%, respectively). IRE1β and MUC2 proteins were predominately expressed in colonic epithelial cells and expression was decreased in the tumor compared with the control group. In conclusion, the downregulation of IRE1β and MUC2 may reduce the ability of colon tissues to resist inflammation, thus promoting the occurrence and development of colonic tumors.

Background:The 12-hydroxy-14-dehydroandrographolide (DP) is a predominant component of the traditional herbal medicine Andrographis paniculata (Burm. f.) Nees (Acanthaceae). Recent studies have shown that DP exhibits potent anti-cancer effects against oral and colon cancer cells.Objective:This investigation examined the potential effects of DP against osteosarcoma cell.Methods:A cell analyzer was used to measure cell viability. The cell growth and proliferation were performed by Flow cytometry and BrdU incorporation assay. The cell migration and invasion were determined by wound healing and transwell assay. The expression of EMT related proteins was examined by Western blot analysis.Results:In this study, we found that DP treatment repressed osteosarcoma (OS) cell growth in a dose-dependent manner. DP treatment significantly inhibited OS cell proliferation by arresting the cell cycle at G2/M phase. In addition, DP treatment effectively inhibited the migration and invasion abilities of OS cells through wound healing and Transwell tests. Mechanistic studies revealed that DP treatment effectively rescued the epithelialmesenchymal transition (EMT), while forced expression of SATB2 in OS cells markedly reversed the pharmacological effect of DP on EMT.Conclusion:Our data demonstrated that DP repressed OS cell growth through inhibition of proliferation and cell cycle arrest; DP also inhibited metastatic capability of OS cells through a reversal of EMT by targeting SATB2. These findings demonstrate DP’s potential as a therapeutic drug for OS treatment.

We investigated the effects of isoalantolactone on cell growth inhibition and underlying cell death mechanisms in SKOV3 human ovarian cancer cells. The effects of isoalantolactone on cell proliferation and cell cycle were examined by EdU incorporation assay and DNA content assay. Western blotting was performed to determine the protein expression effects of isoalantolactone on cell cycle‑related proteins, autophagic regulators and PEA‑15. Autophagic vacuoles were observed by acridine orange staining. PEA‑15 knockdown by siRNA was used to confirm that PEA‑15 was involved in isoalantolactone‑induced autophagy of SKOV3 cells. Isoalantolactone inhibited the viability and proliferation of SKOV3 cells in a dose‑ and time‑dependent fashion. Isoalantolactone induced cell cycle arrest at G2/M phase and decreased the expression of cell cycle‑related proteins cyclin B1 and CDK1 in SKOV3 cells. Accordingly, isoalantolactone also induced SKOV3 cell autophagy via accumulation of autophagic vacuoles in the cytoplasm, increased Beclin1 protein expression, and increased LC3 cleavage. Furthermore, we observed that isoalantolactone‑induced autophagy was through increased PEA‑15 expression and the phosphorylation of ERK, whereas less change was observed to autophagy on SKOV3 cells through PEA‑15 knockdown by siRNA. Isoalantolactone‑induced autophagic cell death was further confirmed by pretreatment with the autophagy inhibitor 3‑methyladenine (3‑MA). In conclusion, isoalantolactone induced cell cycle arrest and autophagy and inhibited cell proliferation of SKOV3 cells via the upregulated PEA‑15 expression and the phosphorylation of ERK.

The gene expression profile chip of salt-resistant wheat mutant RH8706-49 under salt stress was investigated. The overall length of the cDNA sequence of the probe was obtained using electronic cloning and RT-PCR. An unknown gene induced by salt was obtained, cloned, and named TaDi19 (Triticum aestivum drought-induced protein). No related report or research on the protein is available. qPCR analysis showed that gene expression was induced by many stresses, such as salt. Arabidopsis thaliana was genetically transferred using the overexpressing gene, which increased its salt tolerance. After salt stress, the transgenic plant demonstrated better physiological indicators (higher Ca2+ and lower Na+) than those of the wild-type plant. Results of non-invasive micro-test technology indicate that TaDi19-overexpressing A. thaliana significantly effluxed Na+ after salt treatment, whereas the wild-type plant influxed Na+. Chelating extracellular Ca2+ resulted in insignificant differences in salt tolerance between overexpressing and wild-type A. thaliana. Subcellular localization showed that the gene encoding protein was mainly located in the cell membrane and nucleus. TaDi19 was overexpressed in wild-type A. thaliana, and the transgenic lines were more salt-tolerant than the control A. thaliana. Thus, the wheat gene TaDi19 could increase the salt tolerance of A. thaliana.

Overexpression of interleukin (IL)-35 has been found in a variety of malignancies, but the expression status in gastric cancer has yet to be elucidated clearly. In the present study, positive expression of EBI3 and p35 was 63.3% and 70.0% of cases, respectively. EBI3 expression was strongly related with larger tumor size and invasion depth (P

Zinc finger protein 280B (ZNF280B) mediates pro-survival and pro-growth functions in prostate cancer. However, in gastric cancer, its clinical significance remains poorly characterized. In the present study, the expression levels of ZNF280B in 60 patients with gastric cancer were examined using immunohistochemistry. The association between ZNF280B expression and clinicopathological features was assessed. Positive ZNF280B staining was demonstrated for 38 (63.3%) samples out of 60 gastric cancer cases in immunohistochemical analysis. ZNF280B expression was significantly associated with tumor size (P=0.017) and TNM stage (P=0.001). Furthermore, the proliferation index in the positive ZNF280B expression group was significantly higher (38.8±6.2) compared with that of the negative ZNF280B expression group (16.9±8.9; P

Circular RNAs (circRNAs) have proved to play an important role in gastric cancer. In this study, we found that circ_0056618 took part in gastric cancer cell proliferation and survival. The real-time polymerase chain reaction result showed that circ_0056618 was overexpressed in tumor tissues or cells compared with adjacent normal tissues or normal cells and had a negative relationship to gastric cancer patients' survival time. Meanwhile, the inhibition of circ_0056618 suppressed the proliferation and metastasis of gastric cancer cells. Further bioinformatical analysis indicated that circ_0056618 sponged miR-206 to regulate CXCR4 according to the prediction of TargetScan and miRanda. Dual-luciferase reporter assay and Western blot analysis revealed the underlying relationship of circ_0056618, miR-206, and CXCR4. Hence, circ_0056618 negatively regulated miR-206 expression promoting CXCR4 expression. Altogether, circ_0056618 is a potential gastric cancer prognostic marker, as well as a potential therapeutic target to inhibit gastric cancer metastasis.