Effects of FGF21 overexpression in osteoporosis and bone mineral density: a two-sample, mediating Mendelian analysis.

Objective: Fibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density. Methods: We conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results. Results: MR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively. Conclusions: Our study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.

Mechanism exploration of Osteoking in the treatment of lumbar disc herniation based on network pharmacology and molecular docking.

OBJECTIVE: Lumbar disc herniation (LDH) is a common spinal surgical disease. Low back and leg pain caused by LDH is the main factor leading to functional disability, which has caused a serious burden to patients and society. Osteoking can delay the progression of osteoporosis and osteoarthritis, and even has a significant effect on the prevention of deep vein thrombosis after fracture surgery. In recent years, it has been gradually used in the treatment of LDH and has received significant results. However, the underlying mechanism remains unclear. The aim of this study was to predict the mechanism of Osteoking in the treatment of LDH through network pharmacology and verify it by molecular docking method. METHODS: The TCMSP database was used to collect the relevant active components and targets of Osteoking, while the GeneCards, OMIM and DisGeNET databases were utilized to collect the relevant disease targets of LDH. The Venny 2.1.0 software was employed to obtain the intersecting gene targets of Osteoking and LDH. PPI network construction and core target selection were performed using Cytoscape 3.9.0 software. The Metascape database was used for GO and KEGG enrichment analysis of the relevant targets. Finally, molecular docking was conducted using AutoDock software. RESULTS: The study identified 116 potential targets and 26 core targets for the treatment of LDH with Osteoking. Pathways in cancer, Alzheimer's disease, microRNAs in cancer and the IL-17 signalling pathway were among the main involved signalling pathways. Molecular docking results demonstrated that the key targets AKT1, IL-6, ALB, TNF and IL-1ß exhibited relatively stable binding activities with the main active components of Osteoking. CONCLUSIONS: Osteoking can alleviate the symptoms of lumbar disc herniation through the modulation of multiple targets and signalling pathways.

Effect of early enteral nutrition in elderly patients with hip fracture during the perioperative period.

OBJECTIVE: This study aimed to assess the effects of early enteral nutrition (EN) in elderly patients with hip fracture. METHODS: The patients were classified into two groups (with and without EN). We compared the pre- and postoperative albumin (ALB) and inflammatory marker levels of each group and the time spent in bed and quality of life 3 months after surgery between the two groups. RESULTS: The pre- and postoperative IL-6 levels of the experimental group (61.68 ± 51.80 pg/L) were lower than those of the control group (233.11 ± 206.31 pg/L) (P< 0.001). The experimental group spent a shorter period of time in bed (38.75 ± 14.26 days) in comparison to the control group (99.71 ± 56.87 days) (P< 0.001). Quality of life was better in the experimental group than in the control group (P< 0.001). CONCLUSIONS: Early EN reduced the increment of postoperative IL-6 levels and improved healing postoperatively.

miR-142-5p in Bone Marrow-Derived Mesenchymal Stem Cells Promotes Osteoporosis Involving Targeting Adhesion Molecule VCAM-1 and Inhibiting Cell Migration.

Osteoporosis is a systemic bone metabolic disease that is highly prevalent in the elderly population, particularly in postmenopausal women, which results in enhanced bone fragility and an increased susceptibility to fractures. However, the underlying molecular pathogenesis mechanisms still remain to be further elucidated. In this study, in a rat ovariectomy- (OVX-) induced postmenopausal osteoporosis model, aberrant expression of a microRNA miR-142-5p and vascular cell adhesion molecule 1 (VCAM-1) was found by RNA sequencing analysis and qRT-PCR. Using a dual-luciferase reporter assay, we found that miR-142-5p can bind to and decrease expression of VCAM-1 mRNA. Such reduction was prohibited when the miR-142-5p binding site in VCAM-1 3'UTR was deleted, and Western blotting analyses validated the fact that miR-142-5p inhibited the expression of VCAM-1 protein. Bone marrow-derived mesenchymal stem cells (BMMSCs) transfected with miR-142-5p showed a significantly decreased migration ability in a Transwell migration assay. Collectively, these data indicated the important role of miR-142-5p in osteoporosis development involving targeting VCAM-1 and inhibiting BMMSC migration.

miR-542-3p prevents ovariectomy-induced osteoporosis in rats via targeting SFRP1.

Secreted frizzled-related protein-1 (SFRP1) is a negative regulatory molecule of the WNT signaling pathway and serves as a therapeutic target for bone formation in osteoporosis. In this study, we first established an ovariectomized (OVX) rat model to simulate postmenopausal osteoporosis and found significant changes in miR-542-3p and sFRP1 expression by RNA sequencing and qRT-PCR. In addition, there was a significant negative correlation between miR-542-3p and sFRP1 mRNA levels in postmenopausal women with osteoporosis. We found that miR-542-3p inhibited the expression of sFRP1 mRNA by luciferase reporter assay. When the miR-542-3p binding site in sFRP1 3'UTR was deleted, it did not affect its expression. Western blot results showed that miR-542-3p inhibited the expression of SFRP1 protein. The expression of SFRP1 was significantly increased in osteoblast-induced mesenchymal stem cells (MSC), whereas the expression of miR-542-3p was significantly decreased. And miR-542-3p transfected MSCs showed a significant increase in osteoblast-specific marker expression, indicating that miR-542-3p is necessary for MSC differentiation. Inhibition of miR-542-3p reduced bone formation, confirmed miR-542-3p play a role in bone formation in vivo. In general, these data suggest that miR-542-3p play an important role in bone formation via inhibiting SFRP1 expression and inducing osteoblast differentiation.

Correlations between the levels of acute infection markers and serum albumin in elderly patients with hip fracture.

OBJECTIVE: The aim of this study was to explore a clinical index that could predict the decline of serum albumin (ALB) in elderly patients (over 60 years old) with hip fractures in 2014. METHODS: All the data came from the retrospective survey, and the correlations between the ALB changes and acute infection markers were then analyzed using correlation analysis. The changes of infection markers and ALB before and after surgery were compared using the t test. RESULTS: There was no correlation of the serum ALB blood with interleukin-6 (IL-6) (r = 0.072, P = 0.588), C-reactive protein (CRP) (r = -0.249, P = 0.057), or calcitonin (PCT) (r = -0.038, P = 0.775) when patients were admitted, but it was negatively correlated with the total amount of infection markers (TAIMs) (r = -0.301, P = 0.020). The postoperative levels of IL-6 (154.23 ± 177.14 pg/mL) (P < 0.001), CRP (69.52 ± 39.84 mg/L) (P < 0.001), and PCT (1.27 ± 2.4 ng/mL) (P < 0.001) were significantly increased than those before surgery [IL-6 (44.96 ± 54.58 pg/mL), CRP (31.78 ± 29.90 mg/L), and PCT (0.42 ± 1.06 ng/mL)]. The postoperative level of serum ALB (29.93 ± 3.02 g/L) was significantly reduced than that before surgery (33.95 ± 3.69 g/L) (P < 0.001). The serum ALB level was negatively correlated with IL-6 (r = -0.333, P = 0.015) before surgery, but not correlated with TAIMs (r = -0.256, P = 0.061). The serum ALB level was negatively correlated with IL-6 (r = -0.292, P = 0.034) and TAIMs (r = -0.271, P = 0.050) after surgery. CONCLUSIONS: The serum IL-6 level could predict the changes of ALB during the disease process.

N-terminal Pro-B-type Natriuretic Peptide is Associated with Arterial Stiffness as Measured According to the Brachial-ankle Pulse Wave Velocity in Patients with Takayasu Arteritis.

AIM: Takayasu arteritis (TA) is associated with increased cardiovascular morbidity and mortality, and the degree of arterial stiffness is an independent predictor of cardiovascular mortality in a variety of diseases. In addition, the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, have been found to be higher in patients with TA than in healthy controls. In this study, we aimed to investigate the relationship between the plasma NT-proBNP levels and arterial stiffness in patients with TA. METHODS: Seventy-two patients with TA were recruited in this study. The participants were analyzed with respect to the NT-proBNP levels, cardiovascular risk factors, TA-related variables and arterial stiffness assessed according to the brachial-ankle pulse wave velocity (baPWV). The patients were divided into two groups based on the mean baPWV, and the association between the NT-proBNP and baPWV values was tested using uni- and multivariate analyses. RESULTS: Twenty-four patients (33.3%) were classified into the high-baPWV group. The body mass index (p=0.035), systolic blood pressure (p＜0.001), diastolic blood pressure (p=0.001), mean blood pressure (p＜0.001), plasma NT-proBNP levels (p=0.036) and total cholesterol levels (p=0.030) were significantly higher in the high-baPWV group than in the low-baPWV group. A stepwise multiple linear regression analysis revealed the mean blood pressure (p＜0.001), age (p=0.002), and NT-proBNP level (p=0.002) to be independent determinants of the ba-PWV after adjusting for other confounding factors. CONCLUSIONS: The plasma NT-proBNP levels are independently associated with the degree of arterial stiffness measured according to the baPWV in patients with TA.

The association of red blood cell distribution width with anemia and inflammation in patients with Takayasu arteritis.

BACKGROUND: Red blood cell distribution width (RDW) has been shown to be related to both anemia and inflammation in various diseases. However, the role of RDW in patients with Takayasu arteritis (TA) is unknown. Therefore, we investigated the association of RDW with anemia, inflammation, and disease activity in TA. METHODS: RDW was determined in 156 patients with TA and in 156 control subjects. Anemia status and disease activity were defined according to the World Health Organization and National Institutes of Health criteria, respectively. RESULTS: RDW was significantly increased in patients with anemia (14.6±2.2) compared with those without anemia (13.6±1.3, p<0.001) and control subjects (12.7±0.6, p<0.001). Regardless of the presence of anemia, RDW showed correlation with high-sensitivity C-reactive protein (hs-CRP) (both p<0.05). RDW was higher in active TA than inactive TA in patients without anemia (14.1±1.5 vs. 13.3±1.1, p=0.001). Moreover, multiple regression analysis showed that hs-CRP and mean corpuscular volume were independently associated with RDW. CONCLUSIONS: RDW is influenced by both anemia and inflammation, and RDW may be a useful marker to assess disease activity in patients without anemia.

The role of cardiac pacing in carotid sinus syndrome: a meta-analysis.

PURPOSE: Cardiac pacing can be used to treat carotid sinus syndrome (CSS), but clinical studies have shown conflicting results. We conducted a systematic review and meta-analysis to evaluate the role of pacing for CSS. METHODS: A systematic search of publications in PubMed, Embase, and the Cochrane Library without language restriction was performed. Prospective randomized studies that compared cardiac pacing with standard therapy or pacing with different algorithms were included if the recurrence of syncope or the number of falls was observed. RESULTS: Eight studies enrolling 540 patients were identified. In open-label studies, the recurrence of syncope was reduced significantly by cardiac pacing compared with standard therapy. The recurrence of syncope was not different between single- and dual-chamber pacing, but a lower rate of patients with pre-syncope was observed in the group with dual-chamber pacing. Double-blind clinical studies failed to observe the role of cardiac pacing for preventing falls in patients with CSS. CONCLUSION: The results of meta-analysis supported the use of cardiac pacing for patients with dominant cardioinhibitory CSS.

Relationships between use of statins and arterial stiffness in normotensive and hypertensive patients with coronary artery disease.

BACKGROUND: Statins improve arterial stiffness in patients with coronary artery disease (CAD). Hypertension is a predominant contributor of arterial stiffening. However, the influence of hypertension on the effect of statins for improving arterial stiffness in CAD patients has seldom been investigated. Therefore, in this study, we investigated the relationships between statin use and arterial stiffness in normotensive and hypertensive CAD patients. METHODS: Brachial-ankle pulse wave velocity (ba-PWV) was measured in 437 patients, including 220 hypertensive CAD patients (121 used statins, 99 did not) and 217 normotensive CAD patients (105 used statins, 112 did not). The normotensive and hypertensive CAD patients were matched according to age, sex, and body mass index (BMI). RESULTS: In the normotensive and hypertensive CAD patients, lipid profiles were significantly improved in the statin group compared with the non-statin group. No significant differences in the administered statins (i.e., atorvastatin, simvastatin, rosuvastatin, and pravastatin) and statin therapy duration were found between normotensive and hypertensive CAD patients (all P > 0.05). No significant correlation of ba-PWV and statin therapy duration was found in all CAD patients, normotensive CAD patients, or hypertensive CAD patients (all P > 0.05). ba-PWV in the statin group was significantly lower than that in the non-statin group in normotensive CAD patients ((1331.68 ± 167.52) cm/s vs. (1468.61 ± 244.54) cm/s, P = 0.002) but not in hypertensive CAD patients (P > 0.05). In multiple linear regression analyses, statin therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients (P = 0.018) but not in hypertensive CAD patients (P > 0.05). CONCLUSIONS: Statins may significantly improve arterial stiffness in CAD patients, and hypertension may probably influence the effectiveness of statin therapy in improving arterial stiffness in this population. Further studies are required to investigate the effect of statins on arterial stiffness in normotensive and hypertensive CAD patients.

Effect of arotinolol on left ventricular function in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To evaluate the efficacy and safety of long-term treatment with arotinolol in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS: Sixty-three patients with IDCM were evaluated at baseline and after 12-month therapy with arotinolol. The conventional therapy for congestive heart failure was continued throughout the study with arotinolol as the only beta-blocker. Left ventricular function was assessed with the New York Heart Association functional class and two-dimensional echocardiography. RESULTS: After 12-month arotinolol treatment, there was a significant improvement in left ventricular systolic function. Left ventricular end-systolic dimension significantly decreased from 59.52 +/- 8.83 mm to 50.89 +/- 8.17 mm (P < 0.001). Left ventricular ejection fraction significantly increased from 27.39% +/- 7.94% to 41.13% +/- 9.45% ( P < 0.001). Left ventricular mass index decreased from 150.47 +/- 42.42 g/m2 to 141.58 +/- 34.36 g/m2 (P < 0.01). No adverse events leading to premature discontinuation of study drug occurred. CONCLUSION: In this preliminary study, 12-month arotinolol treatment has a favorable effect on left ventricular function in patients with IDCM, and it is safe and well tolerated.

[MMP-9 gene -1562C/T polymorphism in aortic dissection in Chinese hypertensive patients].

OBJECTIVE: To investigate the association of matrix metalloproteinase 9 (MMP-9) gene -1562C/T polymorphism with the pathogenesis and site involved range of aortic dissection in Chinese population. METHODS: 142 hypertensive patients with aortic dissection and 130 hypertensive patients without aortic dissection were enrolled. Genomic DNAs were extracted from peripheral blood leucocytes. MMP-9 gene -1562C/T polymorphism was determined with PCR-RFLP. MMP-9 gene -1562C/T genotype and allele frequency were compared between hypertensive patients with aortic dissection and without. In addition, associations of MMP-9 gene -1562C/T polymorphism with clinical aspects were analyzed in hypertensive patients with aortic dissection. RESULTS: There was a significant difference in the T allele frequency of the C-1562T MMP-9 polymorphism between the two groups, with more T allele (17.6%) observed in hypertensive patients with aortic dissection as compared with these without (11.2%) (P = 0.033). The genotype distribution for the MMP-9 -1562C/T polymorphism in hypertensive patients with aortic dissection (-1562CC: 69.0%; -1562 CT: 26.8%; -1562TT: 4.2%) and those without (-1562CC: 79.2%; -1562CT: 19.2%; -1562TT: 1.6%; P = 0.118) showed no remarkable difference, but hypertensive patients with aortic dissection possessing T allele showed a higher odds ratio for involving ascending aorta (OR = 2.063, 95% CI = 0.998 - 4.264, P = 0.049) as compared with those without T allele. CONCLUSIONS: The T variant of MMP-9 gene -1562C/T polymorphism was significantly associated with aortic dissection in hypertensive patients and may represent an important genetic component contributing to aortic dissection susceptibility. Furthermore, hypertensive patients with aortic dissection possessing MMP-9 gene -1562T allele are more prone to involvement of ascending aorta.