Metformin inactivates the cGAS-STING pathway through autophagy and suppresses senescence in nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is a complex process involving many factors, among which excessive senescence of nucleus pulposus cells is considered to be the main factor. Our previous study found that metformin can inhibit senescence in nucleus pulposus cells; however, the mechanism of such an action was still largely unknown. In the current study, we found that metformin inactivates the cGAS-STING pathway during oxidative stress. Furthermore, knockdown of STING (also known as STING1) suppresses senescence, indicating that metformin might exert its effect through the cGAS-STING pathway. Damaged DNA is a major inducer of the activation of the cGAS-STING pathway. Mechanistically, our study showed that DNA damage was reduced during metformin treatment; however, suppression of autophagy by 3-methyladenine (3-MA) treatment compromised the effect of metformin on DNA damage. In vivo studies also showed that 3-MA might diminish the therapeutic effect of metformin on IVDD. Taken together, our results reveal that metformin may suppress senescence via inactivating the cGAS-STING pathway through autophagy, implying a new application for metformin in cGAS-STING pathway-related diseases.

The association between vertical laminar fracture and recurrent kyphosis after implant removal of Thoracolumbar burst fracture: a retrospective study.

BACKGROUND: Surgeons often encounter recurrent kyphosis of Cobb angle following thoracolumbar burst fracture surgery. Some factors affecting postoperative correction loss have been studied in previous studies, but few have examined the relationship between laminar fractures and postoperative loss of correction. METHODS: The clinical data of 86 patients with thoracolumbar burst fracture who met the inclusion criteria and were admitted to our Department of Spine Surgery between 2013 and 2020 was retrospectively analyzed. To examine the association between laminar fracturs and postoperative correction loss, demographic and radiographic characteristics of the two groups were analyzed. RESULTS: The presence or absence of laminar fractures was statistically different between the two groups (P < 0.05). Binary logistic regression analysis showed that laminar fractures and preoperative Cobb were statistically significant in the two groups. There were statistically significant differences in the degree of injury of laminar fractures in the coronal plane between the two groups (P < 0.05). CONCLUSION: This study investigated that the presence or absence of laminar fractures and preoperative Cobb contribute to loss of correction after thoracolumbar burst fracture surgery. There was a statistically significant difference between full-length and partial-length laminar fractures on the loss of postoperative correction of thoracolumbar burst fractures with laminar fractures.

Complications and radiographic changes after implantation of interspinous process devices: average eight-year follow-up.

PURPOSE: This study aims to evaluate complications, clinical outcomes, and radiographic results following Coflex implantation. METHODS: We retrospectively studied 66 patients who had decompressive surgery combined with Coflex implantation to treat lumbar spinal stenosis. All imaging data were collected and examined for imaging changes. Clinical outcomes, included Oswestry Disability Index (ODI), back and leg visual analog scale (VAS) scores, were evaluated before surgery, six months after surgery and at the last follow-up. The number of complications occurring after five years of follow-up was counted. All reoperation cases were meticulously recorded. RESULTS: 66 patients were followed up for 5-14 years. The VAS and ODI scores were significantly improved compared with baseline. Heterotopic Ossification (HO) was detectable in 59 (89.4%). 26 (39.4%) patients had osteolysis at the contact site of Coflex with the spinous process. Coflex loosening was detected in 39 (60%) patients. Spinous process anastomosis was found in 34 (51.5%) patients. There was a statistically significant difference in the VAS score of back pain between patients with and without spinous process anastomosis. Nine cases of lumbar spinal restenosis were observed, and prosthesis fracture was observed in one case. CONCLUSION: Our study identified various imaging changes after Coflex implantation, and majority of them did not affect clinical outcomes. The majority of patients had HO, but osteolysis and Coflex loosening were relatively rare. The VAS score for back pain of these patients was higher if they have spinous process anastomosis. After five-year follow-up, we found lumbar spinal restenosis and prosthesis fracture cases.

Development of a Deep-Learning Model for Diagnosing Lumbar Spinal Stenosis Based on CT Images.

STUDY DESIGN: Retrospective study. OBJECTIVES: This study aimed to develop an initial deep-learning (DL) model based on computerized tomography (CT) scans for diagnosing lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging is commonly used for diagnosing lumbar spinal stenosis due to its high soft tissue resolution, but CT is more portable, cost-effective, and has wider regional coverage. Using DL models to improve the accuracy of CT diagnosis can effectively reduce missed diagnoses and misdiagnoses in clinical practice. MATERIALS AND METHODS: Axial lumbar spine CT scans obtained between March 2022 and September 2023 were included. The data set was divided into a training set (62.3%), a validation set (22.9%), and a control set (14.8%). All data were labeled by two spine surgeons using the widely accepted grading system for lumbar spinal stenosis. The training and validation sets were used to annotate the regions of interest by the two spine surgeons. First, a region of interest detection model and a convolutional neural network classifier were trained using the training set. After training, the model was preliminarily evaluated using a validation set. Finally, the performance of the DL model was evaluated on the control set, and a comparison was made between the model and the classification performance of specialists with varying levels of experience. RESULTS: The central stenosis grading accuracies of DL Model Version 1 and DL Model Version 2 were 88% and 83%, respectively. The lateral recess grading accuracies of DL Model Version 1 and DL Model Version 2 were 75% and 71%, respectively. CONCLUSIONS: Our preliminarily developed DL system for assessing the degree of lumbar spinal stenosis in CT, including the central canal and lateral recess, has shown similar accuracy to experienced specialist physicians. This holds great value for further development and clinical application.

Continuous intravertebral injection of fasudil hydrochloride in the treatment of cerebral vasospasm.

BACKGROUND AND OBJECTIVE: Cerebral vasospasm is a serious complication of subarachnoid hemorrhage (SAH) and is associated with clinical deterioration and mortality. The objective of this study is to investigate the effect of continuous intravertebral artery (cIVA) injection of fasudil hydrochloride on delayed cerebral vasospasm (CVS). MATERIAL AND METHODS: Forty white rabbits were alloted into groups: (i) seven-day (cIVA injection of fasudil hydrochloride for seven days after injection of blood) group, (ii) five-day (cIVA injection of fasudil hydrochloride for five days from the third day after injection of blood) group, (iii) intravenous treatment (intravenous infusion of fasudil hydrochloride after the first blood injection twice a day) group, and (iv) control group. All the rabbits in all the four groups underwent selective vertebrobasilar angiography. The pathological changes in the basal artery were observed by light and electron microscopy. Fasudil hydrochloride injection (2ml:30mg) was provided by Tianjin Chase Sun Pharmaceutical Company Limited. RESULTS: Severe CVS occurred after subarachnoid hemorrhage (SAH) in the control group, whereas, it was significantly lower after intravertebral artery and intravenous injection of fasudil hydrochloride. The difference between the intravenous and intravertebral artery groups was statistically significant on the seventh day. CONCLUSIONS: The effect of cIVA injection of fasudil hydrochloride in treating delayed CVS due to SAH at different time points was better than intravenous administration.

Serum CXCL12 levels are associated with stroke severity and lesion volumes in stroke patients.

OBJECTIVE: Previous studies had shown that CXC chemokine ligand-12 (CXCL12) might play a significant role in stroke. The aim of this study was to test the serum baseline CXCL12 levels in Chinese patients with acute ischemic stroke (AIS). METHODS: All consecutive patients with first-ever AIS from January 2013 to June 2014 were recruited to participate in the study. CXCL12 and National Institutes of Health Stroke Scale were measured at the time of admission. Logistic regression analysis was used to evaluate the risk of stroke according to serum CXCL12 levels. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in diagnosing stroke. RESULTS: From 306 screened patients, a total of 239 patients with first-ever AIS were included in this study. The results indicated that the serum CXCL12 levels were significantly higher in AIS patients as compared to normal controls (P < 0.0001). Serum CXCL12 were positively correlated with infarct volume(r = 0.307, P < 0.0001) and stroke severity(r = 0.288, P < 0.0001). After adjusting for all other possible covariates, CXCL12 was a stroke predictor with an adjusted OR of 2.047 [95% confidence interval (CI), 1.781-2.352; P < 0.0001]. Based on the ROC curve, the optimal cutoff value of serum CXCL12 levels as an indicator for auxiliary diagnosis of AIS was projected to be 3.4 ng/ml, which yielded a sensitivity of 87.9% and a specificity of 72.0%, with the area under the curve at 0.902 (95% CI, 0.875-0.929). CONCLUSION: Our study demonstrated that serum CXCL12 levels increased significantly following AIS, and these changes in serum CXCL12 were positively correlated with infarct volume and stroke severity in Chinese sample.

Hydraulic tomography for detecting fracture zone connectivity.

Fracture zones and their connectivity in geologic media are of great importance to ground water resources management as well as ground water contamination prevention and remediation. In this paper, we applied a recently developed hydraulic tomography (HT) technique and an analysis algorithm (sequential successive linear estimator) to synthetic fractured media. The application aims to explore the potential utility of the technique and the algorithm for characterizing fracture zone distribution and their connectivity. Results of this investigation showed that using HT with a limited number of wells, the fracture zone distribution and its connectivity (general pattern) can be mapped satisfactorily although estimated hydraulic property fields are smooth. As the number of wells and monitoring ports increases, the fracture zone distribution and connectivity become vivid and the estimated hydraulic properties approach true values. We hope that the success of this application may promote the development and application of the new generations of technology (i.e., hydraulic, tracer, pneumatic tomographic surveys) for mapping fractures and other features in geologic media.