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The primary objective of this study was to explore the extensive implications and complex molecular interactions arising from the confluence of excessive glucocorticoids and RANKL on the differentiation process of BMM into osteoclasts, profoundly impacting osteoporosis development. The methodology encompassed X-ray analysis and HE staining for evaluating bone loss in mice, while immunohistochemical staining was utilized to observe phosphorylated SHP2 (p-SHP2) expression. The assessment of several phosphorylated and total protein expression levels, including NF-κB, SHP2, SYK, JAK2, TAK1, NFATC1, c-fos, and Cathepsin K, was conducted via Western blotting. Additional experiments, involving CCK8 and monoclonal proliferation assays, were undertaken to determine BMM proliferation capacity. Immunofluorescence staining facilitated the quantification of TRAP fluorescence intensity. In vivo analysis revealed that glucocorticoid surplus triggers SHP2 signaling pathway activation, accelerating osteoporosis progression. Western blot results demonstrated that SHP2 inhibition could decrease the expression of specific proteins such as p-NF-κB and p-SHP2, with minimal effects on p-SYK levels. In vitro findings indicated that glucocorticoid and RANKL interaction activates the SHP2 pathway through NF-κB and SYK pathways, enhancing expressions of p-JAK2, p-TAK1, NFATC1, c-fos, and Cathepsin K, thereby promoting BMM to osteoclast transformation. Conclusion: Excessive glucocorticoids and RANKL interaction advance osteoclast differentiation from BMM by activating the SYK/SHP2/NF-κB signaling pathway, expediting osteoporosis progression.

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Background: Evidence indicates that the addition of ezetimibe to statin therapy reduces cardiovascular events. However, the impact of ezetimibe-statin combination therapy on coronary plaque regression, plaque stabilization, and diameter stenosis remains a matter of controversy. Methods: We performed electronic searches in PubMed, Web of Knowledge, and the Cochrane Central Register of Controlled Trials to identify eligible trials assessing the effects of ezetimibe-statin combination therapy versus statin monotherapy reporting at least one outcome among total atheroma volume (TAV), minimum fibrous cap thickness (FCT), lumen volume (LV), and lumen area (LA) derived from intravascular imaging modalities of intravascular ultrasound (IVUS) and optical coherence tomography (OCT). We used the random-effects model and performed trial sequential analysis (TSA) during this meta-analysis. Results: Eleven articles with a total of 926 individuals (460 in the dual-lipid-lowering therapy group and 466 in the statin monotherapy group) were included in the final meta-analysis. Compared to statin monotherapy, ezetimibe-statin combination therapy was associated with significantly decreased TAV [WMD = -3.17, 95% CI (-5.42 to -0.92), and p = 0.006], with no effect on the LV of the coronary artery [WMD = -0.52, 95% CI (-2.24 to 1.21), and p = 0.56], the LA of the coronary artery [WMD = 0.16, 95% CI (-0.10-0.42), and p = 0.22], or minimum FCT thickness [WMD = 19.11, 95%CI (-12.76-50.97)]. Conclusion: In patients with coronary artery disease, ezetimibe-statin combination therapy resulted in a significant regression in TAV compared to statin monotherapy, whereas no overall improvements of minimum FCT or lumenal stenosis were observed.

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In this study, based on the concrete damaged plasticity (CDP) model in the ABAQUS software, various plastic damage factor calculation methods were introduced to obtain CDP parameters suitable for reactive powder concrete (RPC) materials. Combined with the existing tests for the bending performance of steel-reinforced RPC beams, the CDP parameters of the RPC material were input into ABAQUS to establish a finite element model considering the bond and slip between the steel and RPC for numerical simulation. The load-deflection curve obtained by the simulation was compared with the measured curve in the experiment. The results indicated that on the basis of the experimentally measured RPC material eigenvalue parameters, combined with the appropriate RPC constitutive relationship and the calculation method of the plastic damage factor, the numerical simulation results considering the bond-slip were in good agreement with the experimental results with a deviation of less than 10%. Thus, it is recommended to select a gentle compressive stress-strain curve in the descending section, an approximate strengthening model of the tensile stress-strain curve, and to use the energy loss method and Sidoroff's energy equivalence principle to calculate the RPC plastic damage parameters.

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OBJECTIVE: This study aimed to explore the correlation between the SRY-related high-mobility-group box gene 4 (SOX4) 3' untranslated region (UTR) single nucleotide polymorphism (SNP) and osteoporosis susceptibility. METHODS: The study recruited 330 osteoporosis patients (the case group) and 330 non-osteoporosis patients (the control group) in Sichuan Chengdu First People's Hospital and Zibo Central Hospital from August 2016 to August 2019. Sanger sequencing was used to analyze the genotypes of SOX4 gene rs79958549, rs139085828, and rs201335371 loci. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction between the SOX4 gene rs79958549, rs139085828, and rs201335371 loci and the clinical characteristics of the subjects. RESULTS: The risk of osteoporosis in the carriers of A allele at SOX4 rs79958549 was 5.40 times that in the carriers of the G allele (95% CI 3.25-8.96, P < 0.01). The risk of osteoporosis in the carriers of the A allele at SOX4 rs139085828 was 1.68 times that in the carriers of the G allele (95% CI 1.45-1.85, P < 0.01). The risk of osteoporosis in the carriers of the T allele at SOX4 rs201335371 was 0.54 times that in the carriers of the C allele (95% CI 0.43-0.69, P < 0.01). The SOX4 gene rs79958549, rs139085828, and rs201335371 A-A-C haplotype (OR = 5.14, 95% CI 2.45-10.57, P < 0.01) were associated with increased risk of osteoporosis and G-G-T haplotype was significantly associated with decreased risk of osteoporosis (OR = 0.48, 95% CI 0.38-0.62, P < 0.01). The interaction among the factors of sex, smoking, drinking, rs79958549, rs201335371 was the best model for osteoporosis prediction, and the risk for osteoporosis in 'high-risk combination' was 2.74 times that of 'low-risk combination' (95% CI 1.01-7.43, P = 0.04). Multiple logistic regression analysis revealed that the risk factors for osteoporosis were BMD (OR = 5.85, 95% CI 2.88-8.94, P < 0.01), T score (OR = 8.54, 95% CI 5.66-10.49, P < 0.01), Z score (OR = 3.77, 95% CI 2.15-8.50, P < 0.01), rs79958549 SNP (OR = 6.92, 95% CI 3.58-8.93, P < 0.01), and rs139085828 SNP (OR = 2.36, 95% CI 1.85-4.27, P < 0.01). The protective factor for osteoporosis was rs201335371SNP (OR = 0.48, 95% CI 0.32-0.75, P < 0.01). CONCLUSION: The SOX4 gene SNPs rs79958549, rs139085828, and rs201335371 loci were significantly associated with osteoporosis risk.

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Objective: To study the association of the expression levels of long noncoding RNA Taurine-upregulated gene 1 (lncRNA TUG1) and TUG1 polymorphisms with knee osteoarthritis (KOA). Materials and Methods: A total of 255 KOA patients and 255 controls from May 2017 to December 2019 were selected for the study. Sanger sequencing was conducted to detect the genotypes of the TUG1 rs5749201, rs7284767, and rs886471 loci in all study subjects. Unconditional logistic regression analysis was used to calculate odds ratios and 95% confidence intervals, and the associations between the TUG1 rs574901, rs7284767 and rs886471 loci and KOA risk were analyzed. Multifactor dimensionality reduction was used to analyze the interactions among alleles at the three TUG1 loci examined. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of TUG1 lncRNA in plasma. Results: A total of 255 KOA patients and 255 control subjects completed the study. After adjusting for the factors of gender, age, body mass index, smoking history, drinking history, and family history, we found that the carriers of the A allele of the TUG1 rs5749201 locus were 1.36 times more likely to develop KOA than the carriers of the T allele (95% confidence interval [CI] = 1.05-1.75, p = 0.02); the G allele of the rs7284767 locus was a protective factor for KOA (odds ratio [OR] = 0.71, 95% CI = 0.54-0.92, p = 0.01); and the allelic variation at rs886471 G > T led to an increased risk of KOA by 2.34 times (95% CI = 1.53-3.57, p < 0.01). We also found that the GAG haplotype for the three loci was significantly associated with the increased risk of KOA (OR = 2.77, 95% CI = 1.67-4.57, p < 0.01). There was no correlation found between the TUG1 rs886471, rs5749201, and rs7284767 single nucleotide polymorphisms loci and the severity of KOA. The allelic variation at TUG1 rs5749201 T > A, rs886471 T > G were associated with decreased levels of TUG1 lncRNA in the plasma of the subjects, while the allelic variation at rs7284767 A > G was associated with increased levels of TUG1 lncRNA in plasma (p = 0.01, p < 0.01, p < 0.01). Conclusion: Plasma TUG1 lncRNA levels and loci at the TUG1 rs5749201, rs7284767, and rs886471 loci are associated with KOA risk.

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As a regulator of osteogenesis, microRNA-218 (miR-218) is reported to promote osteogenesis of mesenchymal stem cells (MSCs). However, the in vivo osteogenic effect of miR-218 remains elusive. In this study, miR-218 was confirmed to promote osteogenic differentiation of MSCs by stimulating the alkaline phosphatase activity, calcium nodule formation, and osteogenic marker gene expression. For in vivo study, the miR-218-overexpressing BMSCs were locally administrated into the fracture sites in a femur fracture mouse model. Based on the X-rays, micro-computed tomography, mechanical testing, histology, and immunohistochemistry examinations, miR-218 overexpression improved new bone formation and accelerated fracture healing. These findings suggest that miR-218 may be a promising therapeutic target for bone repair in future clinical applications.

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The atp6 and apt9 gene fragments associated with cytoplasmic male sterility (CMS) were cloned from the mitochondrial DNA of a ramie (Boehmeria nivea (L.) Gaud.) cytoplasmic male sterile line and its maintainer and restorer lines using PCR and degenerated primer strategy. The primers were designed according to the reserved sequences in the encoding region of mitochondrial genes atp6 and atp9 of some dicotyledons from GenBank. These fragments did not have complete encoding region but showed the homology of 94% and 85% with atp6 and atp9 genes from the referred dicotyledons in GenBank. The complete atp6 and atp9 genes including the complete open reading frames were cloned by means of amplifying the 3' and 5'end unknown sequences of these gene fragments using DNA Walking method. The atp6 gene showed no difference among ramie male sterile line, maintainer and restorer lines at mtDNA sequence, transcription and translation control and protein level. However, compared to the maintainer and restorer lines, the atp9 gene of the male sterile line was different and deletion in several bases at the 3' end of the encoding region. An abnormally high expression of atp9 gene in the male sterile line at the budding stage and full-bloom stage was analyzed by RT-PCR analysis. These results indicated that the variation in DNA sequence and/or abnormality in expression of atp9 gene in the male sterile line maybe closely related to ramie CMS.

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