External validation of predictive models for new vertebral fractures following percutaneous vertebroplasty.

OBJECTIVE: To investigate the external validation and scalability of four predictive models regarding new vertebral fractures following percutaneous vertebroplasty. METHODS: Utilizing retrospective data acquired from two centers, compute the area under the curve (AUC), calibration curve, and Kaplan-Meier plot to assess the model's discrimination and calibration. RESULTS: In the external validation of Zhong et al.'s 2015 predictive model for the probability of new fractures post-vertebroplasty, the AUC for re-fracture at 1, 2, and 3 years postoperatively was 0.570, 0.617, and 0.664, respectively. The AUC for Zhong et al.'s 2016 predictive model for the probability of new fractures in neighboring vertebrae was 0.738. Kaplan-Meier plot results for both models indicated a significantly lower incidence of re-fracture in low-risk patients compared to high-risk patients. Li et al.'s 2021 model had an AUC of 0.518, and its calibration curve suggested an overestimation of the probability of new fractures. Li et al.'s 2022 model had an AUC of 0.556, and its calibration curve suggested an underestimation of the probability of new fractures. CONCLUSION: The external validation of four models demonstrated that the predictive model proposed by Zhong et al. in 2016 exhibited superior external generalization capabilities.

Validation of the Palliative Prognostic Index, Performance Status-Based Palliative Prognostic Index and Chinese Prognostic Scale in a home palliative care setting for patients with advanced cancer in China.

BACKGROUND: The predictive value of the prognostic tool for patients with advanced cancer is uncertain in mainland China, especially in the home-based palliative care (HPC) setting. This study aimed to compare the accuracy of the Palliative Prognostic Index (PPI), the Performance Status-Based Palliative Prognostic Index (PS-PPI), and the Chinese Prognosis Scale (ChPS) for patients with advanced cancer in the HPC setting in mainland China. METHODS: Patients with advanced cancer admitted to the hospice center of Yuebei People's Hospital between January 2014 and December 2018 were retrospectively calculated the scores according to the three prognostic tools. The Kaplan-Meier method was used to compare survival times among different risk groups. Receiver operating characteristic curve analysis was used to assess the predictive value. The accuracy of 21-, 42- and 90-day survival was compared among the three prognostic tools. RESULTS: A total of 1863 patients were included. Survival time among the risk groups of all prognostic tools was significantly different from each other except for the PPI. The AUROC of the ChPS was significantly higher than that of the PPI and PS-PPI for 7-, 14, 21-, 42-, 90-, 120-, 150- and 180-day survival (P < 0.05). The AUROC of the PPI and PS-PPI were not significantly different from each other (P > 0.05). CONCLUSIONS: The ChPS is more suitable than the PPI and PS-PPI for advanced cancer patients in the HPC setting. More researches are needed to verify the predictive value of the ChPS, PPI, and PS-PPI in the HPC setting in the future.

Advanced oxidation protein products induce annulus fibrosus cell senescence through a NOX4-dependent, MAPK-mediated pathway and accelerate intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IVDD) is closely associated with senescence. Annulus fibrosus (AF) cell senescence is a crucial driver of AF tissue tearing and fissures, thereby exacerbating IVDD. Increased advanced oxidative protein products (AOPPs) were found in human degenerative discs and aged rat discs and may be involved in IVDD. This study aimed to explore the mechanism of AOPPs-induced senescence in AF cells. Methods: The pathological effects of AOPPs in vivo were investigated using a rat lumbar disc persistent degeneration model and a rat caudal disc puncture model. Rat primary AF cells were selected as in vitro models, and AOPPs were used as direct stimulation to observe their pathological effects. Setanaxb (NOX1/4 inhibitor), apocynin (NADPH oxidase inhibitor) and adenovirus (ADV) packed NADPH oxidase 4 (NOX4) specific shRNAs were used for pathway inhibition, respectively. Finally, adeno-associated viruses (AAVs) packed with NOX4-specific blocking sequences were used to inhibit the in vivo pathway. Results: AOPPs accumulated in the rat lumbar and caudal degenerative discs. Intra-discal loading of AOPPs up-regulated the expression of NOX4, p53, p21, p16, IL-1ß, and TNF-α, ultimately accelerating IVDD. Exposure of AOPPs to AF primary cells up-regulated NOX4 expression, induced phosphorylation of mitogen-activated protein kinases (MAPK), triggered senescence and increased IL-1ß and TNF-α. Apocynin, setanaxib, and ADV pre-cultured AF cells abrogated AOPPs-induced senescence. AAV-mediated inhibition of NOX4 expression in vivo reduced the expression of p53, p21, p16, IL-1ß and TNF-α in vivo and delayed IVDD. Conclusions: AOPPs induced AF cell senescence through a NOX4-dependent and MAPK-mediated pathway.

Pretreatment with kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury.

Spinal cord injury (SCI) is a devastating injury that characterized by oxidative stress and inflammatory response. Kaempferol is reported to be an anti-neuroinflammation in neurologic disorders. Nevertheless, the role and mechanism of kaempferol in SCI remains unclear. The present study aims to investigate effects of kaempferol on SCI and its possible underlying mechanisms in in vivo and in vitro models. A C5 hemi-contusion injury was induced in Sprague-Dawley rats to investigate the neuroprotective effects of kaempferol after SCI. For in vitro study, the BV2 microglia cell lines were pretreated with or without kaempferol. A combination of molecular and histological methods was used to clarify the mechanism and explore the signaling pathway both in vivo and in vitro. One-way analysis of variance (ANOVA) was conducted with Bonferroni post hoc tests to examine the differences between groups. The in vivo studies showed that kaempferol could improve the recovery of hindlimb motor function and ameliorate tissue damage in the spinal cord after SCI. Moreover, administration of kaempferol reduced microglia activation and oxidative stress level in the spinal cord. The in vitro studies showed that kaempferol suppressed the microglia activation resulting from the administration of LPS with ATP to BV-2 cells. Pretreated BV2 cells with kaempferol reduced the generation of reactive oxygen species (ROS) by inhibiting NADPH oxidase 4, and then, suppressed the phosphorylation of p38 MAPK and JNK, which subsequently inhibited nuclear translocation of NF-κB p65 to express pro-inflammatory factors. We also observed that kaempferol could inhibite the pyroptosis related proteins (NLRP3 Caspase-1 p10 ASC N-GSDMD) and reduce the release of IL-18 and IL-1ß. In conclusion, kaempferol was able to reduce oxidative stress and inflammatory response through down-regulation of ROS dependent MAPKs- NF-κB and pyroptosis signaling pathway, which suggested that kaempferol might be a novel promising therapeutic agent for SCI.

Feasibility and Safety of Cervical Kinematic Magnetic Resonance Imaging in Patients with Cervical Spinal Cord Injury without Fracture and Dislocation.

OBJECTIVE: To evaluate the feasibility and safety of cervical kinematic MRI (KMRI) in patients with cervical spinal cord injury without fracture and dislocation (CSCIWFD). METHODS: This was a single-institution case-only study. Patients with CSCIWFD were enrolled in our institution from February 2015 to July 2019. Cervical radiography and CT were performed first to exclude cervical tumors, and major fracture or dislocation. Then neutral static and kinematic (flexion and extension) MRI was performed for patients who met the inclusion criteria under the supervision of a spinal surgeon. Any adverse events during the KMRI examination were recorded. Patients received surgical or conservative treatment based on the imaging results and patients' own wishes. The American Spinal Injury Association impairment scale (AIS) grade and the Japanese Orthopedic Association (JOA) score were evaluated on admission, before KMRI examination, and after KMRI examination. For the surgical patients, AIS grade and JOA score were evaluated again 1 week after the operation. The JOA scores were compared among different time points using the paired t-test. RESULTS: A total of 16 patients (12 men and 4 women, mean age: 51.1 [30-73] years) with CSCIWFD were included in the present study. Clinical symptoms included facial trauma, neck pain, paraplegia, paresthesia, hyperalgesia, sensory loss or weakness below the injury level, and dyskinesia. On admission, AIS grades were B for 2 cases, C for 5, and D for 9. A total of 14 patients underwent neutral, flexion, and extension cervical MRI examination; 2 patients underwent neutral and flexion examination because they could not maintain the position for a prolonged duration. No patient experienced deterioration of neurological function after the examinations. The AIS grades and JOA scores evaluated post-examination were similar to those evaluated pre-examination (P > 0.05) and significantly higher than those on admission (P < 0.05). A total of 12 patients received surgical treatment, 11 of whom underwent anterior cervical discectomy and interbody fusion and 1 underwent posterior C3/4 fusion with lateral mass screws. The remaining 4 patients were offered conservative therapy. None of the patients experienced any complications during the perioperative period. The AIS grade did not change in most surgical patients, except that 1 patient changed from grade C to D 1 week after the operation. The JOA score 1 week after surgery was significantly higher than those on admission and around examination for the surgical patients (P < 0.05). CONCLUSION: Cervical KMRI is a safe and useful technique for diagnosis of CSCIWFD, which is superior to static cervical MRI for therapeutic decision-making in patients with CSCIWFD.

Overexpression of TBL1XR1 confers tumorigenic capability and promotes recurrence of osteosarcoma.

Osteosarcoma is the most common malignant bone tumor in childhood and adolescence; however, the mechanism of this malignancy remains uncertain. Transducin (beta)-like 1 × -linked receptor 1 (TBL1XR1) plays an important role in controlling the transcriptional switch between gene activation and gene repression. However, the clinical significance and the precise biological function of TBL1XR1 in osteosarcoma remain unclear. In the present study, we revealed that TBL1XR1 is markedly upregulated in osteosarcoma cell lines and tissues, at both the mRNA and protein levels. Overexpression of TBL1XR1 dramatically enhanced, whereas inhibition of TBL1XR1 reduced, the cancer stem cell (CSC)-like phenotype and tumorigenicity of osteosarcoma cells, both in vitro and in vivo. Importantly, TBL1XR1 enhanced the tumorigenicity of osteosarcoma cells via activating STAT3 signaling and TBL1XR1 expression correlated significantly with STAT3 phosphorylation in osteosarcoma. Taken together, our results provide new evidence that TBL1XR1 overexpression induces CSCs-like phenotypes and tumorigenic capability of osteosarcoma and might represent a novel therapeutic target for its treatment.