Zhandong Bo

Abstract Background Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to the progression of OS, but its potential molecular regulatory role is still unclear. Based on the ability to couple with exosomes for targeted delivery of signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers for OS. Methods We identified ferroptosis-related miRNAs and messenger ribonucleic acids(mRNAs) in OS using bioinformatics analysis and performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, and used RT-qPCR and IHC to verify the expression level of miR-144-3p and ZEB1. Stable gene expression cell lines were fabricated for in vitro experiments. Cell viability, migration and invasion were determined by CCK-8 and transwell experiment. Use the corresponding reagent kit to detect GSH/GSSG ratio, Fe 2+ level, MDA level and ROS level, and measure the expression levels of GPX4, ACSL4 and xCT through RT-qPCR and WB. We also constructed nude mice model for in vivo experiments. Finally, the stability of the miRNA/mRNA axis was verified through functional rescue experiments. Results Low expression of miR-144-3p and high expression of ZEB1 in OS cell lines and tissues was observed. Overexpression of miR-144-3p can promote ferroptosis, reduce the survival ability of OS cells, and prevent the progression of OS. In addition, overexpression of miR-144-3p can downregulate the expression of ZEB1 in cell lines and nude mice. Knockdown of miR-144-3p has the opposite effect. The functional rescue experiment validated that miR-144-3p can regulate downstream ZEB1, and participates in the occurrence and development of OS by interfering with redox homeostasis and iron metabolism. Conclusions MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of OS cells. Graphical Abstract

AIMS: The aim of this review is to assess the effects of exercise training on the symptoms of depression in heart failure (HF) patients. METHODS AND RESULTS: Randomized controlled trials of exercise training in patients with HF and symptoms of depression were identified. The depression data were pooled using meta-analysis, and 19 studies were identified, with a total of 3447 patients, of which 16 (3226 patients) provided data for the meta-analysis. Exercise training demonstrated significant reductions in the symptoms of depression [standardized mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.21], and its antidepressive effect was consistent in a number of HF groups, such as in ages under and over 65 years (SMD -0.14, 95% CI -0.22 to -0.07 vs. SMD -0.44, 95% CI -0.61 to -0.27) and EFs of <50% (SMD -0.38, 95% CI -0.56 to -0.20), as well as in a range of interventional strategies, including the aerobic mode (SMD -0.40, 95% CI -0.61 to -0.19), centre, home, or combined setting (SMD -0.61, 95% CI -0.95 to -0.27 vs. SMD -0.25, 95% CI -0.44 to -0.07 vs. SMD -0.13, 95% CI -0.21 to -0.05), and short or longer training programmes (≤12 weeks, SMD -0.50, 95% CI -0.73 to -0.27; 12-26 weeks, SMD -0.47, 95% CI -0.82 to -0.11; >26 weeks, SMD -0.12, 95% CI -0.20 to -0.04). The beneficial effects were preserved when blind design trials were considered (SMD -0.14, 95% CI -0.22 to -0.07). CONCLUSION: Exercise training significantly decreased the symptoms of depression in patients with HF. This benefit remained unclear in cases of HF with a normal EF and combined aerobic and strength training. Random controlled trials are needed to verify the benefit of exercise in these populations, and in very old, asymptomatic, and severe HF patients.

BACKGROUND: Fast track surgery (FTS) has been gradually applied in perioperative management of orthopedic surgery, but there still some research suspected that the prognosis of patients is not as expected and the cost is high, the effect of the FTS still urgently needed for support by evidence-based medicine. METHODS: We retrieved RCTs from medical research literature databases. Risk ratios (RR), standard mean difference (SMD), and 95% confidence intervals (CI) were calculated to compare the primary and safety endpoints. RESULTS: Overall, a total of 8886 patients were retrieved from 57 articles, of which 4448 patients (50.06%) were randomized to experimental group whereas 4438 patients (49.94%) were randomized to control group. The result showed that FTS could significantly shorten the length of stay (LOS), decrease the visual analog scale (VAS), reduce the leaving bed time and the hospitalization costs, and improve Harris hip joint function score. The incidence of complications such as respiratory system infection, urinary system infection, venous thrombus embolism (VTE), pressure sore, incision infection, constipation, and prosthesis dislocation also has been decreased significantly. Meanwhile, FTS improved patients' satisfaction apparently. CONCLUSIONS: This meta-analysis reveals that FTS could significantly shorten the length of stay, alleviate the pain, reduce the leaving bed time and the hospitalization costs, and improve hip function. The incidence of complications also has been decreased significantly. Meanwhile, FTS has been spoken highly in patients in terms of nursing satisfaction. Its efficacy and safety were proved to be reliable.

BACKGROUND: Many selective cyclooxygenase (COX-2) inhibitors are currently used in clinical practice. COX-2 inhibitors have good anti-inflammatory, analgesic, antipyretic effects, and gastrointestinal safety. However, the analgesic effects and adverse reactions of COX-2 after total knee/hip arthroplasty (TKA/THA) are not fully known. OBJECTIVE: To evaluate the efficacy and safety of selective COX-2 inhibitors in postoperative pain management in patients receiving TKA/THA. METHODS: Randomized controlled trials (RCTs) were retrieved from medical literature databases. Risk ratios (RR) Std mean difference (SMD) and 95% confidence intervals (CI) were calculated to analyze the primary and safety endpoints. RESULTS: In total, 18 articles (23 trial comparisons) were retrieved comprising 3104 patients. Among them, 1910 patients (61.5%) were randomized to the experimental group whereas 1194 patients (38.5%) were randomized to the control group. The primary endpoints were the patients' VAS score at rest or on ambulation (within 3 days). We found that VAS score in patients that received selective COX-2 inhibitor was significantly lower compared to those of the control group. CONCLUSION: This meta-analysis shows that selective COX-2 inhibitor therapy is effective, safe, and reliable in relieving postoperative pain of THA/TKA.