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.

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.

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.

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.].

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.

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.

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.

A Real-World Study on the Effect of Imrecoxib for Patients with Axial Spondyloarthritis.

Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) have generally been viewed as first-line therapy for axial spondyloarthritis (axSpA). Imrecoxib is a selective COX-2 inhibitor developed independently in China. At present, only one single-center RCT trial has shown that imrecoxib is equally effective as celecoxib in treating axSpA. Based on real-world data, our study aims to explore the efficiency of imrecoxib and TNF inhibitor (TNFi) combined with imrecoxib in treating axSpA. Patients and Methods: A total of 163 patients with axSpA who had more than two follow-up records in 6 months and treated with imrecoxib/celecoxib/TNFi combined with imrecoxib/TNFi combined with celecoxib from the First Affiliated Hospital of Anhui Medical University SpA Real World Database (AHSpA) were selected for analysis of our study. The linear mixed model was used to compare efficacy indexes before and after treatment and between different groups, adjust baseline measurement value and follow-up time. The Kaplan-Meier survival analysis was used to identify the differences in cumulative clinical remission rates between groups with different treatment at the follow-up period. Results: Results showed that after treatment ASDAScrp was slightly improved in imrecoxib group and celecoxib group within 6 months (p < 0.05). CRP, ESR, BASDAI, ASDAScrp, BASFI, occiput to wall distance and finger floor distance all significantly improved in TNFi combined with imrecoxib group and TNFi combined with celecoxib group within 6 months (all p < 0.05). According to the Kaplan-Meier survival curve and Log rank test analysis, the clinical remission rate was not significantly different between different treatment during 24-month follow-up (all p > 0.05). Conclusion: ASDAScrp improved slightly within 6 months after treatment with imrecoxib, and TNFi combined with imrecoxib significantly improved multiple effect indexes in axSpA patients. The efficacy of imrecoxib and celecoxib in the treatment of axSpA is equivalent. Also, they have the same efficacy after being combined with TNFi.

Safety and Effectiveness of Roxadustat in Dialysis-Dependent Patients With Renal Anemia: A Hospital-Based Cohort Study.

Background Randomized controlled trials (RCTs) have shown the efficacy and safety of Roxadustat and conclude that it has the potential to change the treatment for anemia associated with chronic kidney disease. However, the experience of its use from clinical perspectives post-approval is lacking. Aim Using a clinical practice context, this study aims to compare Roxadustat's effectiveness and tolerability with Erythropoietin (EPO) in patients with renal anemia undergoing dialysis. Methods We examined the clinical records of patients with a diagnosis of renal anemia on dialysis who were prescribed Roxadustat or Erythropoietin at the department of nephrology of the First Affiliated Hospital of Gannan Medical University from January 2021 to December 2021. Eligible hemodialysis (HD) or peritoneal dialysis (PD) patients with renal anemia, aged >18 or <75 years, without infection, active bleeding, and malignancy were recruited. These patients received Roxadustat or EPO based on the preferential prescription choice made by the nephrologists of the department. We retrospectively attempted to determine the treatment response measured by the change in hemoglobin rate, from baseline up to six months. We also explored the impact of various factors on the treatment response and reported adverse events. Results A total of 106 patients have been included in the final analysis, with 53 patients in each group. The mean age of the study group was 49.9 ± 13.6 years with the main Hb level at the baseline of 8.1 g/dL ± 1.23 g/dl. The gain of hemoglobin from the baseline averaged over six months was 2.2 ± 2.11 g/dl in the Roxadustat group compared with 1.1 ± 1.67 g/dL in the EPO group (p=0.01). As compared to EPO,Roxadustat reduced the total cholesterol level by -0.59 ± 1.08 mmol/l versus -0.01 ± 1.28 mmol/l (p=0012) and the low-density lipoprotein (LDL) cholesterol by -0.48 ± 1.07 mmol/l versus -0.47 ± 1.05 (p=0.017) in the first three months. Associated factors with a non-response to treatment were age greater than 65 years (OR=6, 95% CI: 1.23-32.46, p=0.02), hypertension (OR=3.5, 95%CI: 0.89-13.25, p=0.060), and heart failure (OR=4.18, 95%CI:4.18 1.04-20.39, p=0.040). Although the proportion of hospitalization and infection was higher in the EPO group and the incidences of gastrointestinal symptoms (vomiting, nausea) and blood transfusions were higher in the Roxadustat group, there were no statistically significant differences. Conclusion Roxadustat improved hemoglobin compared to erythropoietin in patients undergoing dialysis with a safe profile but precautions should be taken for old patients with a cardiovascular medical history.

Synergy of sarcopenia and vitamin D deficiency in vertebral osteoporotic fractures in rheumatoid arthritis.

OBJECTIVES: To explore the synergistic effect of vitamin D deficiency and sarcopenia on vertebral osteoporostic fracture (VF) in patients with rheumatoid arthritis (RA). METHODS: A total of 188 patients with RA and 158 control subjects were enrolled. Bone mineral density (BMD) at the total hip, neck of femur, lumbar vertebra 1-4, and skeletal muscle mass was measured by dual energy X-ray absorptiometry (DXA) and biological electrical impedance, respectively. Serum 25(OH)D was tested by electrochemiluminescence. The prevalence of VF and osteoporosis (OP) were compared between RA and controls. The synergism of sarcopenia and vitamin D deficiency on VF in patients with RA was tested by χ2 test and logistic regression. RESULTS: The prevalence of OP at all measured sites and VF in RA patients were all higher than those in controls (P < 0.0001). The incidence of VF in RA either with sarcopenia or with vitamin D deficiency was higher than for those without sarcopenia or without vitamin D deficiency (χ2 = 5.069, P = 0.027, χ2 = 8.822, P = 0.001). Age, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28, health assessment questionnaire (HAQ), Sharp score, and body mass index (BMI) were significantly different between RA with sarcopenia or not (P < 0.05). Logistic regression analysis found that age (OR = 1.095, 95%, CI: 1.044-1.150, P < 0.0001) was a significant risk factor for VF in patients with RA, while high skeletal muscle mass (SMI) (OR = 0.513, 95% CI: 0.327-0.804, P = 0.004) was a protective factor for VF in RA patients. CONCLUSIONS: VF, sarcopenia, and vitamin D deficiency are common in patients with RA. Sarcopenia and vitamin D deficiency may be risk factors for the incidence of VF in RA patients. KEY POINTS: • RA patients had a higher incidence of OP and VF, also a high prevalence of sarcopenia and vitamin D deficiency. • Vitamin D deficiency and sarcopenia may might have a synergistic effect on VF in RA. • Aging and sarcopenia are risk factors for VF in RA patients, and sarcopenia were associated with disease activity and structural damage.

Effects of repeated transcranial magnetic stimulation in the dorsolateral prefrontal cortex versus motor cortex in patients with neuropathic pain after spinal cord injury: a study protocol.

INTRODUCTION: Neuropathic pain is one of the common complications of spinal cord injuries (SCI), which will slow down the recovery process and result in lower quality of life. Previous studies have shown that repeated transcranial magnetic stimulation (rTMS) of the motor cortex (M1) can reduce the average pain and the most severe pain of neuropathic pain after SCI. The dorsolateral prefrontal cortex (DLPFC) area is a common target of rTMS. Recently, a few studies found that rTMS of DLPFC may relieve the neuropathic pain of SCI. Compared with the M1 area, the efficacy of rTMS treatment in the DLPFC area in improving neuropathic pain and pain-related symptoms in patients with SCI is still unclear. Therefore, our study aims to evaluate the non-inferiority of rTMS in the DLPFC vs M1 in patients with neuropathic pain after SCI, in order to provide more options for rTMS in treating neuropathic pain after SCI. METHODS AND ANALYSIS: We will recruit 50 subjects with neuropathic pain after SCI. They will be randomly assigned to the DLPFC- rTMS and M1-rTMS groups and be treated with rTMS for 4 weeks. Except for the different stimulation sites, the rTMS treatment programmes of the two groups are the same: 10 Hz, 1250 pulses, 115% intensity threshold, once a day, five times a week for 4 weeks. VAS, simplified McGill Pain Questionnaire, Spinal Cord Injury Pain Date Set, Pittsburgh Sleep Quality Index and Hamilton Anxiety Scale will be evaluated at baseline, second week of treatment, fourth week of treatment and 4 weeks after the end of treatment. And VAS change will be calculated. ETHICS AND DISSEMINATION: The Ethics Committee of the Affiliated Hospital of Southwest Medical University has approved this trial, which is numbered KY2020041. Written informed consent will be provided to all participants after verification of the eligibility criteria. The results of the study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2000032362.

Sarcopenia May Be a Risk Factor for Osteoporosis in Chinese Patients with Rheumatoid Arthritis.

PURPOSE: Osteoporosis (OP) has been classically considered a co-morbidity of rheumatoid arthritis (RA). This investigation determined the clinical significance of sarcopenia in patients with RA combined with OP or whether sarcopenia influences RA when combined with OP. MATERIALS AND METHODS: Data pertaining to the duration of RA, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were collected from 549 RA cases and 158 healthy individuals. Disease activity score at 28 joints (DAS28), the body mass index (BMI), health assessment questionnaire (HAQ), bone mineral density (BMD), and Sharp score were compared between the 2 groups. RESULTS: The prevalence of OP (33.3% vs 12.7%, χ 2= 69.992, P < 0.0001) and sarcopenia (61.7% vs 9.0%, χ 2= 135.336, P < 0.01) was greater in patients with RA than in healthy controls. RA patients with sarcopenia had a higher incidence of OP at all measured sites than RA patients without sarcopenia (all P < 0.0001), and the incidence of OP was significantly higher than in patients with mild-to-moderate or severe RA without sarcopenia (P < 0.0001). Differences in age, gender, course of disease, CRP level, ESR, DAS28, BMI, HAQ, BMD, and Sharp score were statistically different between the RA with or without sarcopenia groups (P < 0.01). The incidence of OP and sarcopenia was higher in RA patients treated than not treated with glucocorticoids [GCs] (36.4% vs 29.3%, P < 0.05 and 66.1% vs 56.0%, respectively; P < 0.05). Logistic regression showed that the risk factors for OP in RA individuals were female (OR, 14.671; 95% CI, 6.877-31.300; P < 0.0001), age (OR, 1.100; 95% CI, 1.076-1.124; P < 0.0001), and sarcopenia (OR, 3.561; 95% CI, 2.214-5.726; P < 0.0001). CONCLUSION: OP and sarcopenia are common in RA patients. Sarcopenia may be a risk factor for OP occurrence in Chinese patients with RA.

Presence of subclinical inflammation in axial spondyloarthritis patients with NSAID/anti-TNF-α drug-induced clinical remission.

OBJECTIVE: To investigate the rate of subclinical inflammation in patients with axial spondyloarthritis (axSpA) with nonsteroidal anti-inflammatory drug (NSAID)/anti-tumor necrosis factor (TNF)-α drug-induced clinical remission and to explore factors influencing clinical and imaging remission. METHODS: One hundred twenty-five patients with axSpA followed up for at least 6 months were enrolled in this prospective study and randomly divided into two groups. Ninety patients were treated with anti-tumor necrosis factor (TNF)-α or anti-TNF-α combined with nonsteroidal anti-inflammatory drugs (NSAIDs) (anti-TNF-α treatment group), and thirty-five patients were treated with only NSAIDs (non anti-TNF-α treatment group). The improvements in the clinical remission rate, imaging remission rate, and disease parameters before and after the different treatments were compared. Risk factors for clinical and imaging remission were analyzed by multivariate logistic regression analysis. RESULTS: The clinical and imaging remission rate was increased after treatment especially in the anti-TNF-α group (P < 0.001). The remission rate of imaging in the group with clinical remission was higher than that in the group with clinical non-remission (P < 0.05). After treatment, the remission rates of imaging in the clinical remission and non-remission group were significantly higher than those before treatment (P < 0.0001). The results of multivariate logistic regression analysis showed that higher CRP was a risk factor for failure of clinical remission in axSpA (OR = 2.034, 95% CI:1.595 ~ 2.617, P < 0.001), while higher ASDAScrp was a risk factor for failure of imaging remission (OR = 1.306, 95% CI:1.026 ~ 1.688, P < 0.05). Anti-TNF-α treatment was a protective factor for both clinical (OR = 0.234, 95% CI:0.091 ~ 0.605, P < 0.05) and imaging remission (OR = 0.511, 95% CI:0.286 ~ 0.914, P < 0.05). CONCLUSION: Even after regular treatment, some clinical remission patients continued to have evidence of subclinical inflammation. Higher CRP and ASDAScrp are risk factors for clinical and imaging non-remission in axSpA respectively, Continuous NSAID treatment (more than 1 year) can effectively improve clinical and MRI inflammation in patients, but anti-TNF-α treatment is more beneficial for clinical and imaging remission. Key Points • Some patients achieving ASDAScrp remission status continue to have inflammation when assessed with objective imaging techniques. • MRI can sensitively measure bone marrow inflammation and may provide a more accurate assessment of remission. • Controlling inflammation, especially reducing CRP and ASDAScrp levels, is a key factor for achieving clinical and imaging remission in patients with axSpA.

The Potential Regulatory Mechanism of lncRNA 122K13.12 and lncRNA 326C3.7 in Ankylosing Spondylitis.

This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation [area under the ROC curve (AUC) = 0.739 (0.609-0.870) and p = 0.003], and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation [AUC = 0.870 (0.780-0.959) and p < 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737)]. In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.

Interactive effect of sarcopenia and falls on vertebral osteoporotic fracture in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) had higher incidences of sarcopenia, falls, osteoporosis, and vertebral osteoporotic fractures (VOPF). Sarcopenia was associated with longer disease duration, higher disease activity, and more severe RA. The interactive effect of sarcopenia and falls was associated with a higher risk of VOPF in patients with RA. PURPOSE: Whether sarcopenia and falls are a risk factor for vertebral fracture in RA patients has not been demonstrated. This study aimed to explore the incidence of vertebral osteoporotic fracture (VOPF) and its relationship with sarcopenia and falls in RA patients. METHODS: A total of 474 RA patients and 156 controls were enrolled in this study. Anteroposterior and lateral X-ray examinations of the vertebral column (T4-L4) were used for the semiquantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. Skeletal muscle mass was measured by direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA method). RESULTS: RA patients had an increased risk of sarcopenia (62.4% vs 9.0%, x2 = 47.478, P < 0.001), falls (30.2% vs 3.2%), osteoporosis (OP) (33.5% vs 12.8%, x2 = 134.276, P < 0.001), and VOPF (20.3% vs 3.8%, x2 = 47.478, P < 0.001) than controls. Patients with sarcopenia were more likely to have VOPF than RA without sarcopenia (24.0% vs 14.0%, x2 = 6.802, P = 0.009). RA with sarcopenia and prior falls had the highest incidences of VOPF (36.7%). Older age (OR = 1.056, P < 0.001, 95% CI 1.030-1.083), falls (OR = 2.043, P = 0.003, 95% CI 1.238-3.371), OP (OR = 1.819, P = 0.034, 95% CI 1.046-3.163), and usage of glucocorticoids (GCs) (OR = 1.862, P = 0.022, 95% CI 1.093-3.172) were risk factors for VOPF in RA patients, while a higher skeletal muscle index (SMI) was a protective factor (OR = 0.754, P = 0.038, 95% CI 0.578-0.984) for VOPF in RA patients. CONCLUSIONS: The interactive effect of sarcopenia and falls is associated with a higher risk of VOPF in patients with RA.

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.

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.

Effects of electromyography biofeedback for patients after knee surgery: A systematic review and meta-analysis.

There has been no systematic review evaluating the efficacy of electromyography (EMG) biofeedback after knee surgery recently. This meta-analysis aimed to determine whether EMG-biofeedback is effective for improving the range of motion (ROM), physical function, and pain relief in patients after knee. Randomized controlled trials (RCTs) assessing the effect of EMG-biofeedback after any knee surgery were retrieved from EMBASE, PubMed, Cochrane Library, Physiotherapy Evidence Database, ClinicalTrials.gov, ProQuest. This review identified 773 unique studies, and six RCTs were in the final meta-analysis. EMG-Biofeedback treatment has a significant difference compared to other rehabilitation therapy in knee ROM improving (SMD = -0.48, 95% CI = -0.82 to -0.14, p = 0.006, I2 = 37%). Moreover, there was no significant difference in pain (SMD = -0.33, 95% CI = -0.67 to0.02, p = 0.07, I2 = 41%) and physical function scores (MD = 1.83, 95% CI = -3.48 to7.14, p = 0.50, I2 = 0%). The results illustrate that EMG-biofeedback can improve knee ROM in patients after knee surgery. However, it is not superior to other rehabilitation methods for pain relief and physical function improvement.