Osteoarthritis (OA), the most prevalent age-related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating evidences indicate that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA.33186 was significantly upregulated in IL-1b)treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM)-induced OA mouse model. Knockdown of circRNA.33186 increased anabolic factor (type II collagen) expression and decreased catabolic factor (MMP-13) expression. Knockdown of circRNA.33186 also promoted proliferation and inhibited apoptosis in IL-1b-treated chondrocytes. Silencing of circRNA.33186 in vivo markedly alleviated DMM-induced OA. Mechanistic study showed that circRNA.33186 directly binds to and inhibits miR-127-5p, thereby increasing MMP-13 expression, and contributes to OA pathogenesis. Taken together, our findings demonstrated a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.
Adenosine-to-inosine (A-to-I) RNA editing regulates miRNA biogenesis and function. To date, fewer than 160 miRNA editing sites have been identified. Here, we present a quantitative atlas of miRNA A-to-I editing through the profiling of 201 pri-miRNA samples and 4694 mature miRNA samples in human, mouse, and We identified 4162 sites present in ∼80% of the pri-miRNAs and 574 sites in mature miRNAs. miRNA editing is prevalent in many tissue types in human. However, high-level editing is mostly found in neuronal tissues in mouse and Interestingly, the edited miRNAs in neuronal and non-neuronal tissues in human gain two distinct sets of new targets, which are significantly associated with cognitive and organ developmental functions, respectively. Furthermore, we reveal that miRNA editing profoundly affects asymmetric strand selection. Altogether, these data provide insight into the impact of RNA editing on miRNA biology and suggest that miRNA editing has recently gained non-neuronal functions in human.
Systemic immune-inflammation index (SII), based on lymphocyte (L), neutrophil (N), and platelet (P) counts, was recently developed and reflects comprehensively the balance of host inflammatory and immune status. We explored its prognostic value in localized gastric cancer (GC) after R0 resection and the potential associations with Thymidine phosphorylase (TYMP), which was reported to increase the migration and invasion of gastric cancer cells. A total of 455 GC patients who received D2 gastrectomy were enrolled. Blood samples were obtained within 1 week before surgery to measure SII (SII = P × N/L). TYMP expression was measured on tumor sections by immunohistochemical analysis. Preoperative high SII indicated worse prognosis (HR: 1.799; 95% CI: 1.174-2.757; p = 0.007) in multivariate analysis and was associated with higher pathological TNM stage, deeper local invasion of tumor and lymph node metastasis (all p < 0.001). SII predicted poor overall survival in pathological TNM stage I subgroup also (p < 0.001). Furthermore we found that in high SII group, positive rate of TYMP expression increased (53.7% vs 42.7%, p = 0.046) and TYMP positive patients had higher SII score (median 405.9 vs. 351.9, p = 0.026). SII, as a noninvasive and low cost prognostic marker, may be helpful to identify higher-risk patients after R0 resection, even for stage I GC patients.
Postoperative delirium and its risk factors had been widely reported in several kinds of surgeries; however, there is only one known article relative to postoperative delirium in spinal surgery. We retrospectively examined the incidence of postoperative delirium and the probable risk factors in patients undergoing spinal surgery in our hospital, with the same aged non-delirium patients as controls, over a 6-month period. Studies about postoperative delirium were reviewed and referenced for variable factors collecting in our study. T tests, v 2 test and logistic regression analysis were performed to evaluate the various factors related to postoperative delirium. A total of 18 patients (3.3%), all of them were aged 54 years or older, had postoperative delirium after surgery. Patients without postoperative delirium aged 54 years or older served as the control group. The percentage of patients older than 65 years (P = 0.003), with comorbid diseases such as diabetes mellitus (P = 0.042) or central nervous system disorders (P = 0.013), with a surgical history (P = 0.028) in delirium group was larger than the control group. The absolute number of medications being taken before the operation in the delirium patients was also more than the control group (P = 0.000). The percentage of patients transfused with 800 mL or more blood was also larger (P = 0.024) in delirium group was larger than the control group. Logistic regression analysis showed that central nervous system disorder (OR 6.480), surgical history (OR 3.499), age older than 65 years (OR 3.390), diabetes mellitus (OR 2.981), transfused 800 mL or more blood (OR 2.537), and hemoglobin less than 100 g/L (OR 0.281) were significantly related to the occurrence postoperative delirium. Our findings suggest that postoperative delirium in spinal surgery can also occurred in younger patients and with an acceptable incidence in total. The risk for postoperative delirium is multifactorial. More prospective research is necessary in order to evaluate these and other risk factors in greater detail.
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