RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

Mechanical forces in avian embryo development.

Research using avian embryos has led to major conceptual advances in developmental biology, virology, immunology, genetics and cell biology. The avian embryo has several significant advantages, including ready availability and ease of accessibility, rapid development with marked similarities to mammals and a high amenability to manipulation. As mechanical forces are increasingly recognised as key drivers of morphogenesis, this powerful model system is shedding new light on the mechanobiology of embryonic development. Here, we highlight progress in understanding how mechanical forces direct key morphogenetic processes in the early avian embryo. Recent advances in quantitative live imaging and modelling are elaborating upon traditional work using physical models and embryo manipulations to reveal cell dynamics and tissue forces in ever greater detail. The recent application of transgenic technologies further increases the strength of the avian model and is providing important insights about previously intractable developmental processes.

The cellular dynamics of neural tube formation.

The vertebrate brain and spinal cord arise from a common precursor, the neural tube, which forms very early during embryonic development. To shape the forming neural tube, changes in cellular architecture must be tightly co-ordinated in space and time. Live imaging of different animal models has provided valuable insights into the cellular dynamics driving neural tube formation. The most well-characterised morphogenetic processes underlying this transformation are convergent extension and apical constriction, which elongate and bend the neural plate. Recent work has focused on understanding how these two processes are spatiotemporally integrated from the tissue- to the subcellular scale. Various mechanisms of neural tube closure have also been visualised, yielding a growing understanding of how cellular movements, junctional remodelling and interactions with the extracellular matrix promote fusion and zippering of the neural tube. Additionally, live imaging has also now revealed a mechanical role for apoptosis in neural plate bending, and how cell intercalation forms the lumen of the secondary neural tube. Here, we highlight the latest research on the cellular dynamics underlying neural tube formation and provide some perspectives for the future.

Over-expression of SRD5A3 and its prognostic significance in breast cancer.

OBJECTIVE: The study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches. METHODS: We evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed. RESULTS: Bioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P < 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (all P < 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P = 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P < 0.001), age (P < 0.05), and histologic subtype (P < 0.001) but had no significant relationship with other clinical characteristics (all P > 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (all P < 0.05). CONCLUSIONS: SRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.

A Bibliometric Analysis Using CiteSpace of Publications from 1999 to 2018 on Patient Rehabilitation After Total Knee Arthroplasty.

BACKGROUND Following total knee arthroplasty (TKA), postoperative patient rehabilitation is important to achieve the optimal level of knee function and mobility. Clinical research in this field is growing, and bibliometric analysis of publication may provide direction for research clinicians and raise awareness of research trends, journal selection, and key topics. Therefore, this bibliometric study aimed to analyze the current status and trends during the past two decades, between 1999 and 2018, of publications on rehabilitation after total knee arthroplasty (TKA) and used CiteSpace. MATERIAL AND METHODS The global literature was searched between 2018 to 2019 for publications related to rehabilitation after TKA. Publication data were identified using relevant search terms and the Web of Science Core Collection database. CiteSpace (5.3.R11) software was used to analyze the journals, authors, institutions, countries, cited references, and keywords using standard bibliometric indicators. RESULTS A total of 1,292 publications were retrieved between 1999 to 2018, and the most active journals, countries, authors, and institutions in the field of TKA rehabilitation were identified. Key areas of research included postoperative analgesia, muscle inhibition, range of motion, inhibitors, knee flexion, pain control, self-reporting, spectral analysis, in vivo forces, and rotator cuff repair. The emerging research topics included epidural analgesia, physiotherapy, postoperative analgesia, recovery, and the use of ropivacaine local analgesia. CONCLUSIONS The findings from this bibliometric study provided insight into trends in clinical research publications in the field of rehabilitation following TKA for the past 20 years, including global trends in emerging areas of research.

Identification of gene expression profiles and key genes in subchondral bone of osteoarthritis using weighted gene coexpression network analysis.

Osteoarthritis (OA) significantly influences the quality life of people around the world. It is urgent to find an effective way to understand the genetic etiology of OA. We used weighted gene coexpression network analysis (WGCNA) to explore the key genes involved in the subchondral bone pathological process of OA. Fifty gene expression profiles of GSE51588 were downloaded from the Gene Expression Omnibus database. The OA-associated genes and gene ontologies were acquired from JuniorDoc. Weighted gene coexpression network analysis was used to find disease-related networks based on 21756 gene expression correlation coefficients, hub-genes with the highest connectivity in each module were selected, and the correlation between module eigengene and clinical traits was calculated. The genes in the traits-related gene coexpression modules were subject to functional annotation and pathway enrichment analysis using ClusterProfiler. A total of 73 gene modules were identified, of which, 12 modules were found with high connectivity with clinical traits. Five modules were found with enriched OA-associated genes. Moreover, 310 OA-associated genes were found, and 34 of them were among hub-genes in each module. Consequently, enrichment results indicated some key metabolic pathways, such as extracellular matrix (ECM)-receptor interaction (hsa04512), focal adhesion (hsa04510), the phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway (PI3K-AKT) (hsa04151), transforming growth factor beta pathway, and Wnt pathway. We intended to identify some core genes, collagen (COL)6A3, COL6A1, ITGA11, BAMBI, and HCK, which could influence downstream signaling pathways once they were activated. In this study, we identified important genes within key coexpression modules, which associate with a pathological process of subchondral bone in OA. Functional analysis results could provide important information to understand the mechanism of OA.

Accelerated chemical shift imaging of hyperpolarized (13) C metabolites.

PURPOSE: Chemical shift imaging (CSI) has long been considered the gold standard method for in vivo hyperpolarized (13) C metabolite imaging because of its high sensitivity. However, CSI requires a large number of excitations so it is desirable to reduce the number of RF excitations and the total acquisition time. METHODS: Centric phase encoding and three-dimensional compressed sensing methods were adopted into a CSI acquisition to improve efficiency and reduce the number of excitations required for imaging hyperpolarized metabolites. The new method was implemented on a GE MR750W scanner for routine real time metabolic imaging experiments. RESULTS: Imaging results from phantoms and in vivo animals using hyperpolarized (13) C tracers demonstrate that when the entire CSI dataset is treated as a single object, compressed sensing can be satisfactorily applied to spectroscopic CSI. Centric k-space trajectory data collection also greatly improves the acquisition efficiency. This combination of compressed sensing CSI and acquisition time reduction was used to perform a hyperpolarized (13) C dynamic study. CONCLUSION: Compressed sensing can be satisfactorily applied to conventional CSI in hyperpolarized (13) C metabolite MR imaging to reduce the number of RF excitations and accelerate the imaging speed to take advantage of conventional CSI in providing high sensitivity and a large spectral bandwidth. Magn Reson Med 76:1033-1038, 2016. © 2016 Wiley Periodicals, Inc.

Metabolism of hyperpolarized [1-(13)C]pyruvate through alternate pathways in rat liver.

The source of hyperpolarized (HP) [(13)C]bicarbonate in the liver during metabolism of HP [1-(13)C]pyruvate is uncertain and likely changes with physiology. Multiple processes including decarboxylation through pyruvate dehydrogenase or pyruvate carboxylase followed by subsequent decarboxylation via phosphoenolpyruvate carboxykinase (gluconeogenesis) could play a role. Here we tested which metabolic fate of pyruvate contributed to the appearance of HP [(13)C]bicarbonate during metabolism of HP [1-(13)C]pyruvate by the liver in rats after 21 h of fasting compared to rats with free access to food. The (13)C NMR of HP [(13)C]bicarbonate was observed in the liver of fed rats, but not in fasted rats where pyruvate carboxylation and gluconeogenesis was active. To further explore the relative fluxes through pyruvate carboxylase versus pyruvate dehydrogenase in the liver under typical conditions of hyperpolarization studies, separate parallel experiments were performed with rats given non-hyperpolarized [2,3-(13)C]pyruvate. (13)C NMR analysis of glutamate isolated from the liver of rats revealed that flux from injected pyruvate through pyruvate dehydrogenase was dominant under fed conditions whereas flux through pyruvate carboxylase dominated under fasted conditions. The NMR signal of HP [(13)C]bicarbonate does not parallel pyruvate carboxylase activity followed by subsequent decarboxylation reaction leading to glucose production. In the liver of healthy well-fed rats, the appearance of HP [(13)C]bicarbonate exclusively reflects decarboxylation of HP [1-(13)C]pyruvate via pyruvate dehydrogenase.

MRI and histopathologic study of a novel cholesterol-fed rabbit model of xanthogranuloma.

PURPOSE: To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination. MATERIALS AND METHODS: Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1 -weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2 -weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2* relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1 , T2 , and T2* values of lesions was performed. After imaging, brain specimens were examined using histological methods. RESULTS: In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6 mm(3) and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2* values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2* components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma. CONCLUSION: Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. J. Magn. Reson. Imaging 2016;44:673-682.

A general chemical shift decomposition method for hyperpolarized (13) C metabolite magnetic resonance imaging.

Metabolic imaging with hyperpolarized carbon-13 allows sequential steps of metabolism to be detected in vivo. Potential applications in cancer, brain, muscular, myocardial, and hepatic metabolism suggest that clinical applications could be readily developed. A primary concern in imaging hyperpolarized nuclei is the irreversible decay of the enhanced magnetization back to thermal equilibrium. Multiple methods for rapid imaging of hyperpolarized substrates and their products have been proposed with a multi-point Dixon method distinguishing itself as a robust protocol for imaging [1-(13) C]pyruvate. We describe here a generalized chemical shift decomposition method that incorporates a single-shot spiral imaging sequence plus a spectroscopic sequence to retain as much spin polarization as possible while allowing detection of metabolites that have a wide range of chemical shift values. The new method is demonstrated for hyperpolarized [1-(13) C]pyruvate, [1-(13) C]acetoacetate, and [2-(13) C]dihydroxyacetone. Copyright © 2016 John Wiley & Sons, Ltd.

Complete next-to-leading-order study on the yield and polarization of Υ(1S,2S,3S) at the Tevatron and LHC.

Based on the nonrelativistic QCD factorization scheme, we present the first complete next-to-leading-order study on the yield and polarization of Υ(1S,2S,3S) hadroproduction. By using the color-octet long-distance matrix elements obtained from fits of the experimental measurements on Υ yield and polarization at the Tevatron and LHC, our results can explain the measurements on the yield very well, and for the polarizations of Υ(1S,2S,3S), they are in (good, good, bad) agreement with recent CMS measurement, but still have some distance from the CDF measurement.

Association of sarcopenia and vitamin D deficiency with glucocorticoid-induced osteoporosis in Chinese patients with rheumatoid arthritis.

OBJECTIVES: The study aimed to explore the association of sarcopenia and vitamin D deficiency with glucocorticoid-induced osteoporosis (GIOP) in Chinese patients with rheumatoid arthritis (RA). METHOD: Skeletal muscle mass, serum 25(OH)D levels, and bone mineral density (BMD) were assessed. RESULTS: The prevalence of OP, sarcopenia, and vitamin D deficiency in RA patients was significantly higher than in controls (all P < 0.001). The percentage of GC use was 56.9%, and the prevalence of GIOP was 38.1% in 480 RA patients. The prevalence of OP in RA patients without sarcopenia was lower than that in RA patients with sarcopenia (P < 0.05). In RA patients with and without GC, the prevalence of OP in patients without sarcopenia was significantly lower than that in patients with sarcopenia (P < 0.001 and P < 0.05). Female sex (OR = 54.737; 95% CI: 7.103-421.809; P < 0.0001), age (OR = 1.078; 95% CI: 1.048-1.110; P < 0.0001), sarcopenia, and vitamin D deficiency (OR = 2.250; 95% CI: 1.246-64.065; P = 0.007) were risk factors for GIOP in RA patients. CONCLUSIONS: GIOP is associated with sarcopenia and vitamin D deficiency and is widespread among Chinese patients with RA. Key points ·Percentage of using GC and the prevalence of OP were all high in Chinese patients with RA. ·GIOP was widely existed in Chinese RA patients, which was associated with sarcoprnia and vitamin D deficiency.

A Lifeact-EGFP quail for studying actin dynamics in vivo.

Here, we report the generation of a transgenic Lifeact-EGFP quail line for the investigation of actin organization and dynamics during morphogenesis in vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis. Using high-resolution live imaging approaches, we present the dynamic behaviors and morphologies of cellular protrusions in different tissue contexts. Furthermore, through the integration of live imaging with computational segmentation, we visualize cells undergoing apical constriction and large-scale actin structures such as multicellular rosettes within the neuroepithelium. These findings not only enhance our understanding of tissue morphogenesis but also demonstrate the utility of the Lifeact-EGFP transgenic quail as a new model system for live in vivo investigations of the actin cytoskeleton.

Skeletal muscle index together with body mass index is associated with secondary osteoporosis in patients with rheumatoid arthritis.

OBJECTIVE: The objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA). METHODS: The bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1-4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI. RESULTS: A total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p < 0.0001), and the prevalence of OP (36.1%, 160/443) and sarcopenia (65.2%, 288/443) in the RA patients were higher than those in the controls (12.7%, 20/158, p < 0.0001; 9.0%, 14/156, p < 0.0001). Significant differences in the BMD, FMI, SMI, mineral content, body fat percentage and skeletal muscle mass were found among the RA patients in the different BMI groups (p < 0.05). In RA patients with BMI < 18.5 kg/m2, the prevalence of OP in the RA patients with sarcopenia was similar to that in those without sarcopenia (44.4% vs. 66. 7%, χ2 = 0. 574, p = 0.449). In the RA patients with a normal BMI or who were overweight or obese, prevalence of OP in the RA patients with sarcopenia was significantly higher than that in the RA patients without sarcopenia (42.8% vs. 21.7%, χ2 = 10.951, p = 0.001; 61.1% vs. 13.0%, χ2 = 26.270, p < 0.0001). In the RA patients without sarcopenia, the prevalence of OP in the RA patients in the different BMI groups was different (p = 0.039). In the RA patients with sarcopenia, there was no significant difference in the prevalence of OP among the RA patients in the different BMI groups (p = 0. 128). The linear correlation analysis showed that the SMI in RA patients was positively correlated with the BMD of each site measured and BMI and FMI (p < 0.0001). However, there was a negative linear correlation between SMI and disease duration (p = 0.048). The logistic regression analysis found that SMI (OR = 0.569, p = 0.002, 95% CI 0.399-0.810), BMI (OR = 0.884, p = 0.01, 95% CI 0.805-0.971) and gender (1 = female, 2 = male) (OR = 0.097, p < 0.0001, 95% CI 0.040-0.236) were protective factors for OP in RA, while age (OR = 1.098, p < 0.0001, 95% CI 1.071-1.125) was the risk factor. CONCLUSION: BMI and SMI are associated with the occurrence of OP in RA patients, and both SMI and BMI are important protective factors for OP secondary to RA.

Polarization for prompt J/ψ and ψ(2s) production at the Tevatron and LHC.

With nonrelativistic QCD factorization, we present the first complete next-to-leading order study on the polarization of prompt J/ψ hadroproduction by including feeddown from χ(c)((3)P(J)(1),(3)S(1)(8)) and ψ(2s) which turn out to be very important parts. By using the color-octet long-distance matrix elements obtained from a combined fit of the measurements at the Tevatron and LHC for J/ψ, ψ(2s) and χ(c), the prompt J/ψ polarization predictions are presented, and the results are in agreement with the CDF run I data (except two points), but in conflict with the CDF run II data, while they are close to the ALICE data (inclusive J/ψ). The measurements at the LHC are expected to clarify the situation.

Causal relationship between endometriosis with infertility and ankylosing spondylitis.

Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = - 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.

Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: Mendelian randomization study in European and East Asian populations.

Objective: Associations between diseases of the musculoskeletal system and connective tissue (MSCTD) and breast cancer (BC) have not been elucidated completely. The purpose of this study was to investigate the associations of MSCTD, rheumatoid arthritis (RA), Sjogren syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis (PM), osteoarthritis (OA) of hip or knee, and ankylosing spondylitis (AS) with BC in European populations and East Asian populations using Mendelian randomized (MR) analysis. Methods: The genetic instruments linked to MSCTD, RA, SS, SLE, SSc, DM, PM, OA, and AS were chosen from the EBI database of complete genome-wide association studies (GWAS) summary data and the FinnGen consortium. The associations of genetic variants with BC were extracted from the Breast Cancer Association Consortium (BCAC). Two Sample MR was performed using summary data from GWAS, principally using the inverse variant weighted (IVW) method. Heterogeneity, pleiotropy, and sensitivity analyses were performed to evaluate the robustness of the results by weighted median, MR Egger, simple mode, weighted mode, and leave-one-out analysis. Results: In the European population, causal relationships between RA and BC (OR=1.04, 95%CI: 1.01-1.07, P=0.023), AS and BC (OR=1.21, 95%CI: 1.06-1.36, P=0.013) were confirmed. IVW analysis showed DM (OR=0.98, 95%CI: 0.96-0.99, P=0.026) and PM (OR=0.98, 95%CI: 0.97-0.99, P=0.002) were associated with slightly decreased risks of estrogen receptor (ER)+ BC, and MSCTD was associated with an increased risk of ER- BC (OR=1.85, 95%CI: 1.27-2.44, P=0.039). There was no causal relationship between SLE, SS, SSc, OA, and BC, neither ER+ BC nor ER- BC. However, in the East Asian population, IVW analysis showed that RA (OR=0.94, 95%CI: 0.89-0.99, P=0.0096) and SLE (OR=0.95, 95%CI: 0.92-0.99, P=0.0058) was associated with decreased risks of BC. Conclusions: This study suggests that causal relationships between patients with MSCTD and BC in the European population are different from those in the East Asian population, patients with RA and AS in the European population have an increased risk of BC, patients with MSCTD have increased risk of ER- BC in the European population, while patients with RA and SLE in the East Asian population have decreased risk of BC.

Corrigendum: Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: mendelian randomization study in European and East Asian populations.

[This corrects the article DOI: 10.3389/fonc.2023.1170119.].

Detection of Transdermal Drug Delivery Efficiency by Shock Wave.

OBJECTIVE: This study aimed to observe the drug distribution ex-vivo after transdermal drug delivery (TDD) by Shock Wave (SW) and to explore the different effects of the two types of shock waves. MATERIALS AND METHODS: Nine female Sprague-Dawley (SD) rats were randomly divided into 3 groups: (i) control group; (ii) RESW group (0.35mJ/mm2, 2 Hz, 400 pulse); (iii) FESW group (0.16mJ/mm2, 2 Hz, 400 pulse). Micro positron emission tomography/computed tomography (PET/CT) was used to observe the distribution of [18]F-NaF. Furthermore, 12 SD rats were randomly divided into 4 groups: (i) control group; (ii) FESW group 1 (0.03mJ/mm2, 2 Hz, 400 pulse); (iii) FESW group 2 (0.16mJ/mm2, 2 Hz, 400 pulse); (iv) FESW group 3 (0.35mJ/mm2, 2 Hz, 400 pulse). High-performance liquid chromatography (HPLC) tested diclofenac sodium and glucose percutaneously TDD by FESW. Statistical significance was conducted by analysis of variance of repeated measurement. RESULTS: The micro PET/CT observed FESW could penetrate [18]F-NaF through the skin, while RESW could not. The second study found the higher the energy of the FESW, the more diclofenac sodium and glucose penetration. Repeated measures analysis of variance found a within-subject effect (diclofenac sodium, F = 4.77, p = 0.03), (glucose, F = 8.95, p = 0.006), significant differences between the control group, FESW group 1, and FESW group 2 (p < 0.05). CONCLUSION: The study found that FESW can penetrate [18]F-NaF, sugar and diclofenac sodium into the rat body. FESW has a good indication of drug penetration, which provides new biological evidence for route administration.

Screening Key lncRNAs of Ankylosing Spondylitis Using Bioinformatics Analysis.

Background: Long non-coding RNAs (lncRNAs) are important regulators in ankylosing spondylitis (AS). Few studies have examined the lncRNA-RNA binding protein (RBP) interaction in AS. This study performed bioinformatics analysis and clinical verification to identify key lncRNAs and propose their RBP interaction. Methods: Three GEO datasets of AS were analyzed by differential expression analysis. The differentially expressed lncRNAs between the AS and control groups were screened out, and the intersecting lncRNAs were regarded as target lncRNAs. Functional was performed to identify target lncRNAs by enrichment analysis, co-expressed RNA analysis, and lncRNA-RBP interaction analysis. Finally, this study analyzed the differential expression level and clinical value of lncRNAs between the AS and control groups. Results: Linc00304, linc00926, and MIAT were differentially expressed and upregulated. Enrichment analysis indicated that the key KEGG terms were the T-cell receptor signaling pathway and B-cell receptor signaling pathway. The key molecular function term was protein binding, and the key biological process term was adaptive immune response. In qRT-PCR results, 44 samples were validated. linc00304 expression was positively correlated with bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). linc00926 expression was only positively correlated with ESR, whereas MIAT expression was positively correlated with BASFI, ESR, and CRP. Logistic regression revealed that linc00304, ESR, and CRP were the independent risk factors for BASDAI activation. The area under the curve (AUC) of serum linc00304 level in the diagnosis of AS was 0.687 (cutoff value: 0.413, specificity: 0.423, sensitivity: 0.900). AUC of linc00926 was 0.664 (cutoff value: 0.299, sensitivity: 0.882, specificity: 0.417). AUC of MIAT was 0.623 (cutoff value: 0.432, specificity: 0.443, sensitivity: 0.890) (all P <0.05). Conclusion: Overall, this study uncovered three novel lncRNAs, which were upregulated in AS, and proposed a new lncRNA-RBP-mRNA interaction that might regulate adaptive immune response.