Retrospective review of prospectively collected data. To assess the value of the deformity angular ratio (DAR, maximum Cobb measurement divided by number of vertebrae involved) in evaluating the severity of spinal deformity, and predicting the risk of neurologic deficit in posterior vertebral column resection (PVCR). Although the literature has demonstrated that PVCR in spinal deformity patients has achieved excellent outcomes, it is still high risk neurologically. This study, to our knowledge, is the largest series of PVCR patients from a single center, evaluating deformity severity, and potential neurologic deficit risk. A total of 202 consecutive pediatric and adult patients undergoing PVCRs from November 2002 to September 2014 were reviewed. The DAR (coronal DAR, sagittal DAR, and total DAR) was used to evaluate the complexity of the deformity. The incidence of spinal cord monitoring (SCM) events was 20.5%. Eight patients (4.0%) had new neurologic deficits. Patients with a high total DAR (≥25) were significantly younger (20.3 vs. 29.0 yr, P = 0.001), had more severe coronal and sagittal deformities, were more myelopathic (33.3% vs. 11.7%, P = 0.000), needed larger vertebral resections (1.8 vs. 1.3, P = 0.000), and had a significantly higher rate of SCM events than seen in the low total DAR (<25) patients (41.1% vs. 10.8%; P = 0.000). Patients with a high sagittal DAR (≥15) also had a significantly higher rate of SCM events (34.0% vs. 15.1%, P = 0.005) and a greater chance of neurologic deficits postoperatively (12.5% vs. 0, P = 0.000). For patients undergoing a PVCR, the DAR can be used to quantify the angularity of the spinal deformity, which is strongly correlated to the risk of neurologic deficits. Patients with a total DAR greater than or equal to 25 or sagittal DAR greater than or equal to 15 are at much higher risk for intraoperative SCM events and new neurologic deficits. Level of Evidence: 3

Senescence and apoptosis of the nucleus pulposus cells (NPCs) are essential components of the intervertebral disc degeneration (IDD) process. Senescence and anti-apoptosis treatments could be effective ways to delay or even stop disc degeneration. IDD has been treated with Eucommia ulmoides Oliver (Du Zhong, DZ) and its active ingredients. However, the roles and mechanisms of DZ in NPC apoptosis and senescence remain unclear. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to select the main active ingredients of DZ with the threshold of oral bioavailability (OB) ​≥ ​30% and drug-likeness (DL) ​≥ ​0.2. GSE34095 contained expression profile of degenerative intervertebral disc tissues and non-degenerative intervertebral disc tissues were downloaded for different expression genes analysis. The disease targets genes of IDD were retrieved from GeneCards. The online tool Metascape was used for functional enrichment annotation analysis. The specific effects of the ingredient on IL-1β treated NPC cell proliferation, cell senescence, reactive oxygen species (ROS) accumulation and cell apoptosis were determined by CCK-8, SA-β-gal staining, flowcytometry and western blot assays. A total of 8 active compounds of DZ were found to meet the threshold of OB ​≥ ​30% and DL ​≥ ​0.2 with 4151 drug targets. After the intersection of 879 IDD disease targets obtained from GeneCards and 230 DEGs obtained from the IDD-related GSE dataset, a total of 13 hub genes overlapped. According to functional enrichment annotation analysis by Metascape, these genes showed to be dramatically enriched in AGE-RAGE signaling, proteoglycans in cancer, wound healing, transmembrane receptor protein tyrosine kinase signaling, MAPK cascades, ERK1/2 cascades, PI3K/Akt signaling pathway, skeletal system, etc. Disease association analysis by DisGeNET indicated that these genes were significantly associated with IDD, intervertebral disc disease, skeletal dysplasia, and other diseases. Active ingredients-targets-signaling pathway networks were constructed by Cytoscape, and kaempferol was identified as the hub active compound of DZ. In the IL-1β-induced IDD in vitro model, kaempferol treatment significantly improved IL-1β-induced NPC cell viability suppression and senescence. In addition, kaempferol treatment significantly attenuated IL-1β-induced ROS accumulation and apoptosis. Furthermore, kaempferol treatment partially eliminated IL-1β-induced decreases in aggrecan, collagen II, SOX9, and FN1 levels and increases in MMP3, MMP13, ADAMTS-4, and ADAMTS-5. Moreover, kaempferol treatment significantly relieved the promotive effects of IL-1β stimulation upon p38, JNK, and ERK1/2 phosphorylation. ERK1/2 inhibitor PD0325901 further enhanced the effect of kaempferol on the inhibition of ERK1/2 phosphorylation, downregulation of MMP3 and ADAMTS-4 expression, and upregulation of aggrecan and collagen II expressions. Kaempferol has been regarded as the major active compound of DZ, protecting NPCs from IL-1β-induced damages through promoting cell viability, inhibiting cell senescence and apoptosis, increasing ECM production, and decreasing ECM degradation. MAPK signaling pathway may be involved. This study provides in vitro experimental data support for the pharmacological effects of kaempferol in treating IDD, and lays a solid experimental foundation for its future clinical application in IDD treatment.