RNA splicing is a fundamental step of gene expression. While constitutive splicing removes introns and joins exons unbiasedly, alternative splicing (AS) selectively determines the assembly of exons and introns to generate RNA variants corresponding to the same transcript. The biogenesis of circular RNAs (circRNAs) is inextricably associated with AS. Back-splicing, the biogenic process of circRNA, is a special form of AS. In cancer, both AS and circRNA deviate from the original track. In the present review, we delve into the intricate interplay between AS and circRNAs in the context of cancer. The relationship between AS and circRNAs is intricate, where AS modulates the biogenesis of circRNAs and circRNAs in return regulate AS events. Beyond that, epigenetic and posttranscriptional modifications concurrently regulate AS and circRNAs. On the basis of this modality, we summarize current knowledge on how splicing factors and other RNA binding proteins regulate circRNA biogenesis, and how circRNAs interact with splicing factors to influence AS events. Specifically, the feedback loop regulation between circRNAs and AS events contributes greatly to oncogenesis and cancer progression. In summary, resolving the crosstalk between AS and circRNA will not only provide better insight into cancer biology but also provoke novel strategies to combat cancer. Graphical Abstract

Backgrounds: Profiting from the development of nanomaterials, photothermal therapy (PTT) has been discovered as efficient tumor ablation strategy for breast cancer. Materials and methods: Novel oxygen vacancy-rich tungsten bronze nanoparticles (Na_xWO₃) were synthesized through a simple pyrogenic decomposition process. TEM, XRD, UV-vis-NIR, photothermal conversion ability, and photothermal stability were performed. The viabilities of 293T and 4T1 cells after treating with 200 μg/mL Na_xWO₃ nanoparticles for 24 or 48 hrs were both above 80%, which proved the good biosafety and cytotoxicity of Na_xWO₃ in vitro. Two in vivo breast cancer models, namely percutaneous and intratibial 4T1 models were established and Na_xWO₃ (20 mg/kg) with power intensity of 1.5 W/cm² 980 nm laser photothermal treatment was used in vivo. Results: We successfully synthesized ∼150 nm Na_xWO₃ nanoparticles with desirable PTT effects, as evidenced by the temperature increase from 25.8°C to 41.8°C in 5 mins under the irradiation of 980 nm laser (1 mg/mL). Also, cellular compatibility of Na_xWO₃ nanoparticles was found upon physiologic 293T cells, in contrast with significant cytotoxicity against breast cancer 4T1 cell in vitro dose-dependently. Besides, two in vivo breast cancer models showed the decent tumor ablation ability of Na_xWO₃ nanoparticles, demonstrating percutaneous 4T1 tumor elimination without recurrence during 2 weeks observation as well as intratibial breast cancer inhibition with decreased bone destruction and tumor volume after Na_xWO₃+PTT in vivo. Conclusion: For the first time, we developed a novel oxygen vacancy-rich tungsten bronze nanoparticles (Na_xWO₃) through a simple pyrogenic decomposition process for PTT. Both in vitro and in vivo experiments showed the good PTT ability and tumor ablation effects of synthesized Na_xWO₃ nanoparticles against breast cancer osteolytic bone metastasis. Additionally, our oxygen-deficient Na_xWO₃ nanoparticles will expand the research horizons of PTT nanomaterials.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. The purpose of this study was to evaluate the postoperative pain relief, time to ambulation, and opioid-sparing effects of flurbiprofen axetil (FA) and celecoxib (CX) after total-knee arthroplasty (TKA) surgery. A convenience sample of 300 patients was obtained using a retrospective chart review of patients who underwent TKA and received FA or CX or saline (SA) as control. Institutional review board approval was obtained, and 300 charts of patients who received TKA were reviewed. Visual analog scale (VAS) pain scores up to 6 months postoperatively, opioid requirements, range of knee motion, adverse effects, and length of hospital stay are recorded. Data were analyzed using the Pearson Chi-square where appropriate or the Fisher exact test, and all continuous variables were examined using a Wilcoxon rank test. The results of the study showed no significant differences between the 3 groups for the age, gender, American Society of Anesthesiologists class, number of patients who underwent knee surgery, weight, height, and operation duration. Patients in FA and CX demonstrated significantly reduced pain scores and less morphine consumption at rest and active motion compared to SA in 24 hours after surgery, with lower scores and less opioid requirements in the FA group. However, after 48 hours postoperatively, there are no significant differences between these groups. Intravenous application of 1 mg/kg flurbiprofen axetil twice a day and 200 mg celecoxib once a day improved analgesia and decreased morphine consumption following TKA. When the 2 active drugs were compared, it was found that flurbiprofen axetil was superior to celecoxib in terms of short-term analgesic efficacy and opioid consumption.

Bone and soft tissue sarcomas with complex and varied clinical, imaging, and pathological characteristics cannot be diagnosed and treated by a single discipline, as each discipline has some limitations. This study aimed to explore the role of a multidisciplinary team (MDT) in the diagnosis and treatment of bone and soft tissue sarcomas over the past four consecutive years. The subjects were 269 patients discussed during MDT meetings at a Bone and Soft Tissue Sarcomas Center in South China. The diagnosis, relapse diagnosis, unplanned resection, management of pulmonary nodules, and treatment of refractory and advanced tumors were compared to similar data provided in the literature to (i) determine whether the MDT significantly affected the diagnosis and treatment of bone and soft tissue sarcomas, and (ii) explore trends in the types of patients with bone and soft tissue sarcomas and treatment decision-making since the establishment of the MDT. Results revealed that the MDT significantly improved preoperative diagnostic accuracy for patients with bone and soft tissue sarcomas; the accuracy of diagnosis and relapse diagnosis by the MDT reached 95.42% and 100%, respectively. After an MDT discussion, the positive pathology rate for extended resection after unplanned resection was 81.2%. The overall accuracy of the MDT in determining the nature of pulmonary nodules was 87.1–91.9%. For patients presenting with pulmonary nodules in osteosarcoma, no statistically significant difference in survival was shown between cases discussed by the MDT and those without an MDT discussion (p = 0.5751). Collectively, the MDT can play a positive role in accurate preoperative diagnosis, relapse diagnosis, the decision to extend resection after an unplanned resection, and the diagnostic accuracy of pulmonary nodules.

Background: Breast cancer bone metastasis and osteoporosis are both severe diseases that seriously threaten human health. These diseases are closely associated with osteolytic lesions. And osteoclasts are the key targets of this pathological process. Given the lack of effective preventive or treatment options against these diseases, the exploitation of new pharmacological agents is critically required. Method: We assessed the efficacy of punicalin on receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast formation, F-actin ring formation, gene expression, bone resorption, nuclear factor-κB (NF-κB) as well as on mitogen-activated protein kinase (MAPK) signaling pathways and molecular docking in vitro . The impact of punicalin on breast cancer-induced osteoclastogenesis, breast cancer cell proliferation, and apoptosis were examined. Transwell assays were also performed. Moreover, we evaluated in vivo effects of punicalin in postmenopausal osteoporosis models and breast cancer bone metastasis model by micro-CT scanning and histomorphometry. Results: Punicalin inhibited osteoclast formation, F-actin ring formation, bone resorption, as well as osteoclast-related gene expression by suppressing the NF-κB signaling pathway. In vitro , punicalin also suppressed the breast cancer-induced osteoclastogenesis, and proliferation, migration as well as invasion of MDA-MB-231 cells and dose-dependently promoted their apoptosis. In vivo , punicalin significantly suppressed breast cancer-induced osteolysis, breast cancer-associated bone metastasis, and ovariectomized (OVX)-mediated osteoporosis by repressing osteoclast and breast cancer cell. Conclusion: Punicalin is expected to offer a novel treatment for the prevention of osteolysis diseases, including osteoporosis and breast cancer-associated osteolysis.