Osteosarcoma (OS) is a primary malignant bone tumor that most commonly affects children, adolescents, and young adults. Here, we comprehensively analyze genomic, epigenomic and transcriptomic data from 121 OS patients. Somatic mutations are diverse within the cohort, and only TP53 is significantly mutated. Through unsupervised integrative clustering of the multi-omics data, we classify OS into four subtypes with distinct molecular features and clinical prognosis: (1) Immune activated (S-IA), (2) Immune suppressed (S-IS), (3) Homologous recombination deficiency dominant (S-HRD), and (4) MYC driven (S-MD). MYC amplification with HR proficiency tumors is identified with a high oxidative phosphorylation signature resulting in resistance to neoadjuvant chemotherapy. Potential therapeutic targets are identified for each subtype, including platinum-based chemotherapy, immune checkpoint inhibitors, anti-VEGFR, anti-MYC and PARPi-based synthetic lethal strategies. Our comprehensive integrated characterization provides a valuable resource that deepens our understanding of the disease, and may guide future clinical strategies for the precision treatment of OS.

Background: P. multocida (Pasteurella multocida) is animal-sourced gram-negative coccobacillus which can be transmitted to human through many animals including household pets. P. multocida induced peritoneal dialysisrelated peritonitis has rarely been reported. In recent years, there has been an increase in the incidence of P. multocida induced peritoneal dialysis-related peritonitis, for the reason that patients with PD at home bred household pets. In this study, we present a case of a P. multocida induced peritoneal dialysis-related peritonitis, which is suspected to be caused through intimate contact with a household cat and we have reviewed 28 cases reported before and give suggestions for treatment and the way of prevention. Case presentation: A 75-year-old man with end-stage renal disease (ESRD) for nearly 5 years on continuous ambulatory peritoneal dialysis (CAPD) was admitted to the nephrology department with a 1-week history of abdominal pain and a cloudy peritoneal dialysis effluent. Based on the history, physical examination and laboratory results with the findings in the peritoneal dialysis fluid, a diagnosis of peritoneal dialysis-related peritonitis was confirmed. The final culture of initial peritoneal effluent results indicated the organism was P. multocida. After a 12day antibiotic treatment, the condition of patient was not improved. The patient was switched to ampicillin/ sulbactam (3 g intravenously) twice every day and the condition was improved significantly. On further inquiring, the patient reported that he had had a cat at home and when the patient did CAPD, the cat was usually playing with the tubing or contacting the patient during CAPD. Conclusion: In our case and reviewed cases, P. multocida induced peritoneal dialysis-related peritonitis could be cured by proper antibiotic treatment. If individuals keep the pet away from the PD process, the infection route may be severed. P. multocida induced peritoneal dialysis-related peritonitis does not need catheter removal and exchange with hemodialysis except long-time intractable peritonitis.

Osteosarcoma is the most common primary malignant bone tumor, and there are few ideal clinically available drugs. The bromodomain and extraterminal domain (BET) protein is an emerging target for aggressive cancer, but therapies targeting the BET in osteosarcoma have been unsuccessful in clinical trials to date, and further exploration of specific BET inhibitors is of great significance. In our study, we demonstrated that NHWD-870, a potent BET inhibitor in a phase I clinical trial, significantly inhibited tumor proliferation and promoted cell apoptosis by reversing the oncogenic signature in osteosarcoma. More importantly, we identified NHWD-870 impeded binding of BRD4 to the promoter of GP130 leading to diminished activation of JAK/STAT3 signaling pathway. Furthermore, GP130 knockdown significantly sensitizes the chemosensitivity in vitro. In OS cell-derived xenografts, NHWD-870 effectively inhibited the growth of osteosarcoma. Beyond that, NHWD-870 effectively inhibited the differentiation and maturation of precursor osteoclasts in vitro and attenuated osteoclast-mediated bone loss in vivo. Finally, we confirmed the efficacy of synthetic lethal effects of NHWD-870 and cisplatin in antagonizing osteosarcoma in a preclinical PDX model. Taken together, these findings demonstrate that NHWD-870, as an effective BET inhibitor, may be a potential candidate for osteosarcoma intervention linked to its STAT3 signaling inhibitory activity. In addition, NHWD-870 appears to be a promising therapeutic strategy for bone-associated tumors, as it interferes with the vicious cycle of tumor progression and bone destruction.

Natural biological lumens in the human body, such as blood vessels and the gastrointestinal tract, are important to the delivery of materials. Depending on the anatomic features of these biological lumens, the invention of nano/micromotors could automatically locomote targeted sites for disease treatment and diagnosis. These nano/micromotors are designed to utilize chemical, physical, or even hybrid power in self-propulsion or propulsion by external forces. In this review, the research progress of nano/micromotors is summarized with regard to treatment and diagnosis in different biological lumens. Challenges to the development of nano/micromotors more suitable for specific biological lumens are discussed, and the overlooked biological lumens are indicated for further studies.