Prevalence of osteoporosis in patients awaiting unicompartmental knee arthroplasty: a cross-sectional study.

Objectives: Osteoporosis may contribute to failure of unicompartmental knee arthroplasty (UKA), yet the prevalence of osteoporosis in the population awaiting UKA has not been adequately studied. The objectives of this study were to report the prevalence of osteoporosis in people awaiting UKA and the rate of anti-osteoporosis treatment, and to explore factors associated with osteoporosis prevalence in people awaiting UKA. Methods: Participants awaiting UKA from January 2019 to May 2023 were consecutively enrolled. Participants ' age, gender, BMI, knee K-L score, VAS score, history of previous DXA testing, history of anti-osteoporosis treatment, and possible underlying risk factors were recorded. All participants were given a dual-energy x-ray absorptiometry (DXA) test after the visit. The diagnosis of osteoporosis was made according to the World Health Organization criteria. Compare the prevalence of osteoporosis between people waiting for UKA and the general population. Risk factors associated with osteoporosis were analyzed using multiple linear regression and binary logistic regression models. Results: A total of 340 participants were included in the study, 259 in female and 81 in male, with a mean age of 63.53 years (range: 41-84 years), and all participants completed UKA and had DXA prior to UKA. The prevalence of osteoporosis was 40.88% (44.79% in female and 28.40% in male). The prevalence of osteoporosis was higher in female than in male (p<0.001). The prevalence of osteoporosis in the population waiting for UKA was significantly higher than that in the general population (p < 0.001). DXA testing was performed in 12.06% within 1 year prior to the visit. The percentage of those who had received anti-osteoporosis treatment was 20.59% (20.86% in osteoporosis, 22.39% in Osteopenia and 16.42% in normal bone mass). The correlation between age, gender, body mass index, visual analogue scale score and osteoporosis was statistically significant. Conclusion: Osteoporosis is common in people waiting for UKA, but screening and treatment rates are low. Female patients of advanced age and low weight combined with significant pain should be considered for osteoporosis screening and appropriate treatment before UKA.

Analysis of miRNAs Involved in Mouse Heart Injury Upon Coxsackievirus A2 Infection.

Coxsackievirus A2 (CVA2) has recently been constantly detected, and is associated with viral myocarditis in children. Our previous study demonstrated that CVA2 led to heart damage in a neonatal murine model. However, the molecular mechanism of heart injury caused by CVA2 remains largely unknown. Emerging evidence suggests the significant functions of miRNAs in Coxsackievirus infection. To investigate potential miRNAs involved in heart injury caused by CVA2, our study, for the first time, conducted a RNA-seq in vivo employing infected mice hearts. In total, 87, 101 and 76 differentially expressed miRNAs were identified at 3 days post infection (dpi), 7 dpi and 7 dpi vs 3 dpi. Importantly, above 3 comparison strategies shared 34 differentially expressed miRNAs. These results were confirmed by quantitative PCR (qPCR). Next, we did GO, KEGG, and miRNA-mRNA integrated analysis of differential miRNAs. The dual-luciferase reporter assay confirmed the miRNA-mRNA pairs. To further confirm the above enriched pathways and processes, we did Western blotting and immunofluorescence staining. Our results suggest that inflammatory responses, T cell activation, apoptosis, autophagy, antiviral immunity, NK cell infiltration, and the disruption of tight junctions are involved in the pathogenesis of heart injury caused by CVA2. The dysregulated miRNAs and pathways recognized in the current study can improve the understanding of the intricate interactions between CVA2 and the heart injury, opening a novel avenue for the future study of CVA2 pathogenesis.

Diagnosis, preoperative evaluation, classification and total hip arthroplasty in patients with long-term unreduced hip joint dislocation, secondary osteoarthritis and pseudoarthrosis.

BACKGROUND: Neglected long-term unreduced hip joint dislocation with secondary osteoarthritis and pseudoarthrosis poses a great challenge to hip surgeons. However, as this is an uncommon injury, few studies have systematically investigated these patients. METHODS: We retrospectively reviewed 16 patients from 2010 to 2017. The diagnostic values of three different types of common radiological examinations were evaluated. We evaluated the bone conditions of the original acetabulum and classified the patients into three types (four subtypes). The surgical procedures and prognosis of the patients were also investigated. RESULTS: With the combined application of X-ray, CT scans and 3D reconstruction, 93.8% of these patients (sensitivity = 93.8%, Youden's index = 0.93, intraclass correlation coefficient = 0.95) could be diagnosed correctly. There were 6/16 (37.5%) type A patients, 4/16 (25.0%) type B1 patients, 5/16 (31.3%) type B2 patients and 1/16 (6.3%) type C patient. For patients with type A injury, the surgical procedures for total hip arthroplasty were similar to "standard" total hip arthroplasty. For patients with type B injury, due to atrophy or partial bone deficiency of the original acetabulum, the surgical procedure for total hip arthroplasty was probably similar to those for patients with developmental dysplasia of the hip. For patients with type C injury, the situation was similar to that of revision surgery. The average Harris hip score postoperatively was 89.94 ± 5.78 points (range: 79-98 points). CONCLUSIONS: The new classification system could help surgeons estimate potential difficulties during total hip arthroplasty. The prognosis of most patients after total hip arthroplasty is expected to be excellent or good.

MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma.

PURPOSE: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma. MATERIALS AND METHODS: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments. RESULTS: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61. CONCLUSION: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.

Morin inhibits cell proliferation and fibronectin accumulation in rat glomerular mesangial cells cultured under high glucose condition.

Morin, is a natural bioflavonoid isolated from Chinese herbs of the Moraceae family, has been reported to possess antidiabetic activity. However, the role of morin on glomerular mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation in diabetic condition is still unclear. Therefore, in this study, we investigated the role of morin on cell proliferation and ECM accumulation in rat glomerular MCs cultured under high glucose (HG) condition. Our results showed that morin inhibited HG-induced MC proliferation, arrested HG-induced cell-cycle progression, reversed HG-inhibited expression of p21Waf1/Cip1 and p27Kip1. It also inhibited HG-induced ECM expression, ROS generation and NOX4 expression in MCs. Furthermore, morin suppressed HG-induced phosphorylation of p38 MAPK and JNK1/2 in MCs. These data suggest that morin inhibits HG-induced MC proliferation and ECM expression through suppressing the activation of p38 MAPK and JNK signaling pathways. Thus, morin may be useful for the prevention or treatment of diabetic nephropathy.

Association of EGF Receptor and NLRs signaling with Cardiac Inflammation and Fibrosis in Mice Exposed to Fine Particulate Matter.

ЄAmbient fine particulate matter (PM2.5 ) could induce cardiovascular diseases (CVD), but the mechanism remains unknown. To investigate the roles of epidermal growth factor receptor (EGFR) and NOD-like receptors (NLRs) in PM2.5 -induced cardiac injury, we set up a BALB/c mice model of PM2.5 -induced cardiac inflammation and fibrosis with intratracheal instillation of PM2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days (once per day). After exposure, we found that mRNA levels of CXCL1, interleukin (IL)-6, and IL-18 were elevated, but interestingly, mRNA level of NLRP12 was significant decreased in heart tissue from PM2.5 -induced mice compared with those of saline-treated mice using real-time PCR. Protein levels of phospho-EGFR (Tyr1068), phospho-Akt (Thr308), NLRP3, NF-κB-p52/p100, and NF-κB-p65 in heart tissue of PM2.5 -exposed mice were all significantly increased using immunohistochemistry or Western blotting. Therefore, PM2.5 exposure could induce cardiac inflammatory injury in mice, which may be involved with EGFR/Akt signaling, NLRP3, and NLRP12.

Effects of vitamin D supplementation as an adjuvant therapy in coronary artery disease patients.

OBJECTIVES: Low vitamin D status has been shown to be associated with coronary artery disease. We planned to research the effects of vitamin D3 supplementation on the severity of coronary artery disease. DESIGN: We investigated the effect of 0.5 µg vitamin D3 per day in a randomized, placebo-controlled, double-blind study in 90 stable coronary artery disease patients residing in Beijing. Coronary angiography was performed before and after 6 months of treatment that took place between January and June. 25-Hydroxyvitamin D was measured by chemiluminescence assay. Coronary artery disease severity was assessed by using the SYNTAX scores. RESULTS: In vitamin D supplementation group, there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (19.9 ± 9.8 ng/ml) to 6 months (35.8 ± 12.1 ng/ml; p < 0.001). At 6 months, the primary end point, a difference in the fall of SYNTAX score between the groups was -2.5 (95% CI -5.1 to -0.5; p < 0.001) under intention to treat analysis. Compared with the control group, patients treated with vitamin D3 also had greater decreases in high sensitivity C-reactive protein and renin-angiotensin system activity (p < 0.05). CONCLUSIONS: Vitamin D supplementation has beneficial effects on coronary artery disease; it can be an adjuvant therapy for patients with coronary artery disease.

Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome: the role of hyperglycemia and obesity.

BACKGROUND: Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease (CAD), CAD patients with metabolic syndrome (MS) still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention (PCI). METHODS: Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography (CAG) were enrolled in our study. MS was defined by modified Adult Treatment Panel III criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry (LTA) and thrombelastography (TEG). Clopidogrel resistance was defined as more than 50% adenosine diphosphate (ADP) induced platelet aggregation as measured by TEG. RESULTS: Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG (55% ± 31% vs. 68% ± 32%; P < 0.001) and LTA (29% ± 23% vs. 42% ± 29%; P < 0.001). In the multivariate analysis, elderly [OR (95% CI): 1.483 (1.047-6.248); P = 0.002], obesity [OR (95% CI): 3.608 (1.241-10.488); P = 0.018], high fasting plasma glucose level [OR (95% CI): 2.717 (1.176-6.277); P = 0.019] and hyperuricemia [OR (95% CI): 2.583 (1.095-6.094); P = 0.030] were all statistically risk factors for clopidogrel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without diabetes and obesity [75% (61/81) vs. 43% (67/156); P < 0.001]. CONCLUSIONS: CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopidogrel resistance.