Restoring p53 activity by inhibiting the interaction between p53 and the mouse double minutes clone 2 (MDM2) offers an attractive approach to cancer therapy. Nutlin-3a is a small-molecule inhibitor that inhibits MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. In this study, we determined the efficacy of Nutlin-3a in inducing p53-mediated cell death in osteosarcoma (OS) cell lines both in vivo and in vitro. Targeted disruption of the p53-MDM2 interaction by Nutlin-3a stabilizes p53 and selectively activates the p53 pathway only in OS cells with wild-type p53, resulting in a pronounced anti-proliferative and cytotoxic effect due to G1 cell cycle arrest and apoptosis both in vitro and in vivo. p53 dependence of these alternative outcomes of Nutlin-3a treatment was shown by the abrogation of these effects when p53 was knocked-down by small interfering RNA. These data suggest that the disruption of p53-MDM2 interaction by Nutlin-3a might be beneficial for OS patients with MDM2 amplification and wt p53 status.

Objective: The aim of the present study was to compare the clinical outcomes and quality of life following percutaneous transforaminal endoscopic discectomy (PTED) and microscope‐assisted tubular discectomy (MTD) for lumbar disc herniation (LDH).Methods: This study had a retrospective design. From June 2017 to June 2018, the clinical data of 120 patients with LDH treated with PTED (60 cases, PTED group) and MTD (60 cases, MTD group) were analyzed and followed up for at least 20 months. There were 59 men and 61 women. Patients were aged between 22 and 80 years. The operation time, intraoperative blood loss, incision length, frequency of intraoperative fluoroscopy, cost, hospital stay, types of herniated discs, complications, and clinical outcomes were evaluated. Clinical outcomes were assessed using the visual analog scale (VAS), the Oswestry disability index (ODI), and the modified Macnab criteria. Short‐Form 36 (SF‐36) and the EQ‐5D‐5L were used to evaluate the quality of life of patients. The data between the two groups were compared by independent sample t‐tests. Multiple comparisons between samples were analyzed by analysis of variance.Results: Compared with the MTD group, the PTED group had shorter incision length (9.20 ± 1.19 mm vs 26.38 ± 1.82 mm), less intraoperative blood loss (18.00 ± 4.97 mL vs 39.83 ± 6.51 mL), and shorter hospital stay (5.42 ± 5.08 days vs 10.58 ± 3.69 days) (P = 0.00). PTED was much more appropriate for foraminal and extraforaminal disc herniation. The incidence of paresthesia was lower in the PTED group (6.67% vs 16.67%). At each follow up, the VAS and ODI scores of all patients were significantly improved compared with those before surgery (P = 0.00). At 3 days postoperatively, the lumbar VAS score of the PTED group was significantly lower (1.58 ± 1.00 vs 2.37 ± 1.10, P = 0.00). The excellent rate of the PTED group reached 91.67%, and that of the MTD group reached 93.33%. Compared with the preoperative SF‐36 scores for physiological function, mental health, and social function, the postoperative scores were significantly improved in both groups (P = 0.00). The EQ‐5D‐5L in the PTED group increased from 0.30 ± 0.17 before the operation to 0.69 ± 0.13 after 6 months of follow up (P = 0.00) and 0.73 ± 0.14 after 20 months of follow up. The EQ‐5D‐5L in the MTD group increased from 0.28 ± 0.17 before the operation to 0.68 ± 0.13 after a 6‐month follow up (P = 0.00), and 0.73 ± 0.12 after a 20‐month follow up.Conclusion: Although both PTED and MTD are effective for LDH, PTED is much more appropriate for various types of LDH and has the advantages of the low incidence of low back pain, fewer complications, and early recovery.

Study Design.: Retrospective, observational study. Objective.: To evaluate the ability and value of metagenomic next-generation sequencing (mNGS) in detecting pathogens from spinal infections. Background.: The pathogenic diagnosis of primary spinal infection is challenging. The widespread application of mNGs in clinical practice makes it particularly useful in detecting rare, emerging, and atypical complex infectious diseases. Methods.: From January 2019 to December 2023, a retrospective collection of 120 samples was obtained from patients suspected of spinal infections and undergoing treatment. Pairwise comparisons between traditional laboratory tests and mNGS were conducted for all cases. Results.: Among the 120 cases, 95 were diagnosed as spinal infections, while 25 were classified as non-infectious. Microbiological evidence was found in 59 cases, while 36 cases were clinically diagnosed as spinal infection without definitive microbiological evidence. Rare microorganisms such as Aspergillus fumigatus, Taifanglania major, and Coxiella burnetii were detected by mNGS. The positive rate of mNGS was significantly higher at 88.42% compared to microbiological culture (43.16%), P<0.001. At the genus level, mNGS exhibited a consistency rate of 86.44% (51/59) with confirmed microorganisms. MNGS demonstrated very good agreement with clinically confirmed microorganisms at the genus level (kappa=0.833). The sensitivity, specificity, positive predictive value, and negative predictive value of mNGS were 86.44%, 92.00%, 96.23%, and 74.19%, respectively. Conclusions.: The mNGS test exhibits rapidity, efficiency, and accuracy, rendering it of immense diagnostic and therapeutic value in the realm of spinal infection diseases.