This in vitro experimental study demonstrated that not only structural disruption, but also a single impact injury of the endplate without structural impairment could also initiate intervertebral disc degeneration (IDD), which might be mediated by activation of Piezo1 induced inflammation and abnormal energy metabolism of intervertebral disc cells.

Background ： It has been acknowledged that the intervertebral disc degeneration(IDD) is associated with an aberrant cell-medicated response to structural failures, such as vertebral burst fracture, radial fissures, and endplate fracture. However, whether a momentary impact injury of the endplates without structural disruption, is sufficiently to initiate disc degeneration remains elusive. This study was to further evolve an in vitro momentary impact injury model of IDD and to investigate if a momentary impact load of the endplates without structural disruption could initiate IDD. Methods. Rat spinal segments (from L1/2 to L5/6, n=54) were harvested and randomly assigned into three groups: Control (n=18), Low Impact (12 J/cm 3 , n=18) and High Impact (25 J/cm 3 , n=18). Samples in both of the impact groups were subjected to axial momentary impact load using a custom-made apparatus, and cultured for 14 days. The degenerative process was investigated by using histomorphology and real-time PCR. Results: The discs in both of the impact groups showed significant degenerative changes at 14 days, both of which showed much higher histological scores and up-regulation of the catabolic (MMP-9, MMP-13) genes transcription than that of the control group ( P ＜0.05). The discs with endplate fracture compared to that with intact endplate also showed strongly up-regulated catabolic (MMP-9, MMP-13) genes transcription, and more significant degenerative changes based on the histological scoring ( P ＜0.05). Conclusion: This study demonstrated that a momentary impact load (12 J/cm 3 ) on the spinal segments of the rats could initiate IDD at 14 days after injury and not only endplate fracture but also a momentary impact injury without structural disruption could also promote IDD.

The AJCC (the American Joint Committee on Cancer) ypTNM (post-neoadjuvant pathologic stage group) staging was established based on patients with lymphadenectomy scope less than D2 and did not include ypT0N0 patients with pathologically complete response (PCR). The purpose of this study was to construct a survival predictive model for gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy. Patients and Methods: The multicenter data of 838 gastric cancer patients who received neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy were analyzed retrospectively. These dual center patients were divided into training (n = 671, the Affiliated Hospital of Qingdao University) and validation (n = 167, Qingdao West Coast New Area Central Hospital) cohorts. Based on training cohort, univariate and multivariable COX regression analyses were performed to select the clinicopathological characteristics significantly correlating with overall survival and construct a nomogram. Based on training and validation cohorts, the distinguishing and calibrating capabilities of nomogram was evaluated by the receiver operating characteristic (ROC) curve, Harrell's concordance index (C-index), decision curve analysis (DCA) curve and calibration curve. Results: Platelet-to-lymphocyte ratio (PLR), pathologic stage after neoadjuvant treatment: ypT and ypN stage, tumor regression grade (TRG) became independent variables intimately related to the prognosis and was used to construct nomograms of 3/5-year prognosis. The nomograms showed an accuracy in predicting OS (overall survival) rate, with area under the ROC curve (AUC) of 0.818 (95% CI = 0.753~0.883) and C-index of 0.801 (95% CI = 0.744~0.858) in validation cohort. Calibration curves showed satisfactory agreement between nomogram prediction and actual result, and DCA curves indicated the large positive net benefit and excellent clinical usefulness of nomogram. Conclusion:This study successfully developed a nomogram to predict overall survival of gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy, which might have excellent predictive performance and clinical application value.

Background : Intervertebral disc degeneration is usually attributed to ageing, genetic, mechanical, and nutritional factors et al. It has been acknowledged that the degenerative process is associated with an aberrant cell-medicated response to structural failures, such as vertebral burst fracture, radial fissures, and endplate fracture. Vertebral endplate trauma, due to, Kirschner wire use or drill holes, can induce degenerative changes of the intervertebral disc (IVD). However, whether a single impact injury of the endplates without structural disruption, which is common seen in the clinic, is sufficiently to initiate disc degeneration is still controversial. This study is to further evolve an in vitro impact injury model of IVD and to investigate if a single impact injury of the endplates without structural disruption can initiate intervertebral disc degeneration(IVDD). Methods. Rats spinal segments (from L1/2 to L5/6, n=54) were harvested and randomly assigned into three groups: Control (n=18), Low Impact (12 J/cm 3 , n=18) and High Impact (25 J/cm 3 , n=18). Samples in both of the impact groups were subjected pure axial impact loading using a custom-made apparatus, and cultured for 14 days. The degenerative process was investigated by using histomorphology and real-time PCR. Results: The discs in both of the impact groups showed significant degenerative changes at 14 days, both of which showed much higher histological scores and up-regulation of the catabolic (MMP-9, MMP-13) genes transcription than that of the control group ( P ＜0.05). The discs with endplate fracture compared to that with intact endplate also showed strongly up-regulated catabolic (MMP-9, MMP-13) genes transcription, and more significant degenerative changes based on the histological scoring ( P ＜0.05). No significant difference of anabolic (TGF-β, Col1α1, Col3α1) genes transcription was found between different groups( P ＞0.05). Conclusion: This study demonstrated that a single impact loading (12 J/cm 3 ) on the spinal segments of the rats could initiate IVDD at 14 days after injury and not only endplate impairment but also a single impact loading without structural disruption could also promote IVDD.

Background ： It has been acknowledged that the intervertebral disc degeneration(IDD) is associated with an aberrant cell-medicated response to structural failures, such as vertebral burst fracture, radial fissures, and endplate fracture. However, whether a momentary impact injury of the endplates without structural disruption is sufficiently to initiate disc degeneration remains elusive. This study was to further evolve an in vitro momentary impact injury model of IDD and to investigate if a momentary impact load of the endplates without structural disruption could initiate IDD. Methods. Rats spinal segments (from L1/2 to L5/6, n=54) were harvested and randomly assigned into three groups: Control (n=18), Low Impact (12 J/cm 3 , n=18) and High Impact (25 J/cm 3 , n=18). Samples in both of the impact groups were subjected axial momentary impact load using a custom-made apparatus, and cultured for 14 days. The degenerative process was investigated by using histomorphology and real-time PCR. Results: The discs in both of the impact groups showed significant degenerative changes at 14 days, both of which showed much higher histological scores and up-regulation of the catabolic (MMP-9, MMP-13) genes transcription than that of the control group ( P ＜0.05). The discs with endplate fracture compared to that with intact endplate also showed strongly up-regulated catabolic (MMP-9, MMP-13) genes transcription, and more significant degenerative changes based on the histological scoring ( P ＜0.05). Conclusion: This study demonstrated that a momentary impact load (12 J/cm 3 ) on the spinal segments of the rats could initiate IDD at 14 days after injury and not only endplate fracture but also a momentary impact injury without structural disruption could also promote IDD.