Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Accumulating evidence has revealed that microRNAs (miRNAs) play a crucial role in the progression of OS. In this study, we found that miR-744-5p was the least expressed miRNA in patients with OS by analyzing GSE65071 from the GENE EXPRESSION OMNIBUS (GEO) database. Through real-time quantitative PCR (qRT-PCR), western blotting, colony formation assay, 5-Ethynyl-2-Deoxyuridine (EdU) incorporation assay, transwell migration, and invasion assays, we demonstrated its ability to inhibit the proliferation, migration, and invasion of OS cells in vitro. According to the luciferase reporter assay, transforming growth factor-β1 (TGFB1) was negatively regulated by miR-744-5p and reversed the effects of miR-744-5p on OS. Subcutaneous tumor-forming animal models and tail vein injection lung metastatic models were used in animal experiments, and it was found that miR-744-5p negatively regulated tumor growth and metastasis in vivo. Furthermore, rescue assays verified that miR-744-5p regulates TGFB1 expression in OS. Further experiments revealed that the p38 MAPK signaling pathway is involved in the miR-744-5p/TGFB1 axis. Generally, this study suggests that miR-744-5p is a negative regulator of TGFB1 and suppresses OS progression and metastasis via the p38 MAPK signaling pathway. Graphical Abstract
Objectives: There is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA.Methods: We investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared.Results: The results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = −0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency.Conclusion: We conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid.
Hydrogen sulfide (H2S) in joint fluid acts as a signal molecule to regulate joint inflammation. Direct detection of H2S in joint fluid is of great significance for the diagnosis and treatment of arthritis. However, due to the low volume of joint fluid and low H2S concentration, existing methods face the problem of the insufficient limit of detection. In this study, a highly sensitive biosensor was proposed by designing a primer probe and combining it with hybrid chain reaction (HCR) under the strong interaction between metal ions and H2S to achieve H2S detection. The primer probe containing multiple cytosine (C) sequences was fixed on a gold electrode, and the C–Ag–C hairpin structure was formed under the action of Ag+. In the presence of H2S, it can combine with Ag+ in the hairpin structure to form Ag2S, which leads to the opening of the hairpin structure and triggers the hybridization chain reaction (HCR) with another two hairpin structures (H1 and H2). A large number of double-stranded nucleic acid structures can be obtained on the electrode surface. Finally, Ru(phen)32+ can be embedded into the double chain structure to generate the electrochemiluminescence (ECL) signal. The linear response of the H2S biosensor ranged from 0.1000 to 1500 nM, and the limit of detection concentration of H2S was 0.0398 nM. The developed biosensor was successfully used to determine H2S in joint fluid.
Objective: To investigate the feasibility of pre‐drilling combined with a finger reduction tool for the reduction of difficult‐to‐reduce intertrochanteric fractures.Methods: Patients diagnosed with complicated intertrochanteric fractures during the period from July 2016 to May 2021 at the Affiliated Hospital of our College were enrolled in this study. All patients underwent reduction by pre‐drilling combined with a finger reduction tool followed by fixing with proximal femoral nail antirotation. The outcome of reduction was evaluated by intraoperative fluoroscopy. The operation time, intraoperative fluoroscopy frequency, and incidence of postoperative complications (including infection in the incision area, coxa vara, nail withdrawal, nail breakage, blade cut‐out, lower limb vein thrombosis, and pulmonary embolism) were recorded to evaluate the speed of the operation, the difficulty of the operation, and the prognosis of the patient, respectively. The Harris hip score at 9 months after surgery was used to evaluate the hip recovery.Results: A total of 52 patients (17 men and 35 women), 61–88 (77.54 ± 7.40) years of age were included in the study. There were 14 patients with cardiovascular or cerebrovascular disease, ten patients with diabetes, three patients with Parkinson's disease, and three patients with respiratory diseases. The fractures included in the study were classified according to the Orthopedic Trauma Association 31 classification system as type A2.2 (n = 36) or type A2.3 (n = 16). The time from injury to surgery was 1–11 (3.35 ± 1.78) days, and the operation time ranged 31–101 (65.67 ± 14.17) min. The intraoperative blood loss ranged from 40 to 100 (67.69 ± 18.24) mL, and the number of intraoperative fluoroscopy images obtained was 12 to 32 (20.42 ± 5.27). The Harris hip score at 9 months after surgery ranged from 84 to 94 (90.06 ± 2.15). Patients were followed for 9–16 (10.63 ± 1.61) months. One patient died of acute myocardial infarction at 9 months after surgery. One patient suffered from nail withdrawal 5 months post‐operation and thus underwent hemiarthroplasty.Conclusions: Satisfactory reduction can be achieved using a pre‐drilling femoral trochanter combined with a finger reduction tool for the management of difficult‐to‐reduce complex intertrochanteric fractures. This technique does not increase surgical trauma and also reduces the dose of radiation administered to the patient.