Is local autogenous morselized bone harvested from decompression through a posterior-transforaminal approach sufficient for single-level interbody fusion in the lower lumbar spine?

BACKGROUND: To determine the volume and applicability of local autogenous morselized bone (LAMB) harvested and used during posterior-transforaminal lumbar interbody fusion (P-TLIF) in the lower lumbar spine. METHODS: Clinical and radiographic data of 147 patients (87 males) undergoing P-TLIF from January 2017 to December 2019 for lumbar degenerative diseases were retrospectively analyzed. Computed tomography was used to assess the fusion status (at 6 months, 1 year, and the last follow-up postoperatively), restored disc height, graft fusion area and volume, and the minimum required bone volume (MRBV). Clinical outcomes of P-TLIF were assessed using the Oswestry Disability Index (ODI) and visual analog scale (VAS) for low back pain (LBP) and leg pain (LP). RESULTS: The mean follow-up period was 28.4 ± 4.49 months. The patient's age and diagnosis were correlated to the volume and weight of LAMB (mean volume and weight: 3.50 ± 0.45 mL and 3.88 ± 0.47 g, respectively). The ratio of actual fusion area to the total disc endplate and the ratio of actual fusion volume to the total volume of the disc space were > 40%. MRBV ranged from 1.83 ± 0.48 cm3 to 2.97 ± 0.68 cm3. The proportion of grade 4 or 5 fusions increased from 60.6% at 6 months to 96.6% at the last follow-up. The ODI, VAS-LP, and VAS-LBP scores significantly improved after surgery and remained unchanged during the follow-up. CONCLUSION: When combined with a cage, the volume of LAMB harvested from decompression through the unilateral approach at a single-level is sufficient to achieve a solid interbody fusion in the lower lumbar spine with excellent clinical and radiographic outcomes.

Encapsulation of Hydrophilic and Hydrophobic Peptides into Hollow Mesoporous Silica Nanoparticles for Enhancement of Antitumor Immune Response.

Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP10025-33 and TRP2180-188 , two melanoma-derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after NH2 modification on the inner hollow core and COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8+ and CD4+ T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations.

What is the optimal sequence of decompression for multilevel noncontinuous spinal cord compression injuries in rabbits?

BACKGROUND: In recent years, multilevel spinal cord injuries (SCIs) have gained a substantial amount of attention from clinicians and researchers. Multilevel noncontinuous SCI patients cannot undergo the multiple steps of a one-stage operation because of a poor general condition or a lack of proper surgical approaches. The surgeon subsequently faces the decision of whether to initially relieve the rostral or caudal compression. In this study, we established a spinal cord compression model involving two noncontinuous segments in rabbits to evaluate the effects of differences in decompression order on the functional recovery of the spinal cord. METHODS: A Fogarty catheter was inserted into the epidural space through a hole in T6-7 and advanced 3 cm rostrally or caudally. Following successful model establishment, which was demonstrated by an evaluation of evoked potentials, balloons of different volumes (40 µl or 50 µl) were inflated in the experimental groups, whereas no balloons were inflated in the control group. The experimental groups underwent the first decompression in the rostral or caudal area at 1 week post-injury; the second decompression was performed at 2 weeks post-injury. For 6 weeks post-injury, the animals were tested to determine behavioral scores, somatosensory evoked potentials (SEPs) and radiographic imaging changes; histological and apoptosis assay results were subsequently analyzed. RESULTS: The behavioral test results and onset latency of the SEPs indicated that there were significant differences between priority rostral decompression (PRD) and priority caudal decompression (PCD) in the 50-µl compression group at 6 weeks post-injury; however, there were no significant differences between the two procedures in the 40-µl group at the same time point. Moreover, there were no significant peak-to-peak amplitude differences between the two procedures in the 50-µl compression group. CONCLUSIONS: The findings of this study suggested that preferential rostral decompression was more beneficial than priority caudal decompression with respect to facilitating spinal cord functional recovery in rabbits with severe paraplegia and may provide clinicians with a reference for the clinical treatment of multiple-segment spinal cord compression injuries.

Prospective randomized evaluation of therapeutic decompressive craniectomy in severe traumatic brain injury with mass lesions (PRECIS): study protocol for a controlled trial.

BACKGROUND: For cases of severe traumatic brain injury, during primary operation, neurosurgeons usually face a dilemma of whether or not to remove the bone flap after mass lesion evacuation. Decompressive craniectomy, which involves expansion of fixed cranial cavity, is used to treat intra-operative brain swelling and post-operative malignant intracranial hypertension. However, due to indefinite indication, the decision to perform this procedure heavily relies on personal experiences. In addition, decompressive craniectomy is associated with various complications, and the procedure lacks strong evidence of better outcomes. In the present study, we designed a prospective, randomized, controlled trial to clarify the effect of decompressive craniectomy in severe traumatic brain injury patients with mass lesions. METHODS: PRECIS is a prospective, randomized, assessor-blind, single center clinical trial. In this trial, 336 patients with traumatic mass lesions will be randomly allocated to a therapeutic decompressive craniectomy group or a prophylactic decompressive craniectomy group. In the therapeutic decompressive craniectomy group, the bone flap will be removed or replaced depending on the emergence of brain swelling. In the prophylactic decompressive craniectomy group, the bone flap will be removed after mass lesion evacuation. A stepwise management of intracranial pressure will be provided according to the Brain Trauma Foundation guidelines. Salvage decompressive craniectomy will be performed for craniotomy patients once there is evidence of imaging deterioration and post-operative malignant intracranial hypertension. Participants will be assessed at 1, 6 and 12 months after randomization. The primary endpoint is favorable outcome according to the Extended Glasgow Outcome Score (5-8) at 12 months. The secondary endpoints include quality of life measured by EQ-5D, mortality, complications, intracranial pressure and cerebral perfusion pressure control and incidence of salvage craniectomy in craniotomy patients at each investigation time point. DISCUSSION: This study will provide evidence to optimize primary decompressive craniectomy application and assess outcomes and risks for mass lesions in severe traumatic brain injury. TRIAL REGISTRATION: ISRCTN20139421.

The value of intraoperative intracranial pressure monitoring for predicting re-operation using salvage decompressive craniectomy after craniotomy in patients with traumatic mass lesions.

BACKGROUND: The risk factors of predicting the need for postoperative decompressive craniectomy due to intracranial hypertension after primary craniotomy remain unclear. This study aimed to investigate the value of intraoperative intracranial pressure (ICP) monitoring in predicting re-operation using salvage decompressive craniectomy (SDC). METHODS: From January 2008 to October 2014, we retrospectively reviewed 284 patients with severe traumatic brain injury (STBI) who underwent craniotomy for mass lesion evacuation without intraoperative brain swelling. Intraoperative ICP was documented at the time of initial craniotomy and then again after the dura was sutured. SDC was used when postoperative ICP was continually higher than 25 mmHg for 1 h without a downward trend. Univariate and multivariate analyses were applied to both initial demographic and radiographic features to identify risk factors of SDC requirement. RESULTS: Of 284, 41 (14.4%) patients who underwent SDC had a higher Initial ICP than those who didn't (38.1 ± 9.2 vs. 29.3 ± 8.1 mmHg, P < 0.001), but there was no difference in ICP after the dura was sutured. The factors which have significant effects on SDC are higher initial ICP [odds ratio (OR): 1.100, 95% confidence interval (CI): 1.052-1.151, P < 0.001], older age (OR: 1.039, 95% CI: 1.002-1.077, P = 0.039), combined lesions (OR: 3.329, 95% CI: 1.199-9.244, P = 0.021) and early hypotension (OR: 2.524, 95% CI: 1.107-5.756, P = 0.028). The area under the curve of multivariate regression model was 0.771. CONCLUSIONS: The incidence of re-operation using SDC after craniotomy was 14.4%. The independent risk factors of SDC requirement are initial ICP, age, early hypotension and combined lesions.

Acute bilateral mass-occupying lesions in non-penetrating traumatic brain injury: a retrospective study.

BACKGROUND: Traumatic acute bilateral mass-occupying lesions (TABML) is a common entity in head injury, with high morbidity and mortality. Our aim in this study was to evaluate the benefits of different treatment options and the outcome predictors in patients with TABML. METHODS: From October 2010 to November 2012, a consecutive cohort of patients aged 16-70 years with TABML were retrospectively analyzed based on the clinical and radiological characteristics. Patients with TABML were included if admitted within 24 h after injury and were excluded if they presented with infratentorial lesions, unilateral lesions within the first 24 h after injury, or penetrating head injury. According to their treatment option, patients were divided into three groups: a conservative treatment group, a unilateral surgery group, and a bilateral surgery group. Outcomes were assessed using the Glasgow Outcome Scale (GOS). Binary logistic regression analysis was applied to determine the outcome predictors. RESULTS: Forty-seven patients (58.8%) had severe injuries (Glasgow Coma Scale score (GCS), 3-8) upon admission, and the overall mortality was 31.3% at 6 months post-injury. The mortality was 55.6% in patients who underwent conservative treatment (N = 18), 17.9% in unilateral surgery patients (N = 39), and 34.8% in the bilateral surgery group (N = 23). In the surgical group, the mortality was 53.3% (8 of 15) in those with a GCS of 3-5, which decreased steeply to 14.9% (7 of 47) of those with GCS ≥ 6. On logistic regression analysis, the absence of pupillary reactivity, disappearances of basal cisterns and conservative treatment were related to higher mortality. A lower initial GCS score was associated with an unfavorable outcome. Midline shift tended to be associated with mortality and an unfavorable outcome, although statistical analysis did not show a significant difference. CONCLUSIONS: TABML is suggestive of severe brain injury. As conservative treatment is always associated with a poorer outcome, surgery is advocated, especially in patients with a GCS score of ≥ 6. Whereas the prognostic value of midline shift might be limited because of the counter-mass effect in TABML, the GCS score, the pupillary reactivity, and particularly, the compression of basal cisterns should be emphasized.

Moderate hypothermia treatment in adult patients with severe traumatic brain injury: a meta-analysis.

OBJECTIVES: To evaluate the effect of moderate hypothermia treatment (MHT) in severe traumatic brain injury (sTBI) compared to normothermia management. METHODS: PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library and Google scholar were searched up to December 2012. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the mortality and clinical neurological outcome of the adult patients with sTBI were collected and calculated in a fixed-effects model or a random-effects model. Summary effect estimates were stratified by study design and ethnicity. Egger's regression asymmetry tests were utilized for detecting the publication bias. RESULTS: The overall estimates showed that MHT could reduce the mortality (hypothermia vs. normothermia, RR = 0.86, 95% CI = 0.73-1.01, p = 0.06) and unfavourable clinical neurological outcomes (RR = 1.21, 95% CI = 0.95-1.53, p = 0.12) for traumatic brain injured patients without statistical significance. Moreover, the further stratification sub-group analysis indicated that MHT presented a significant reduction (RR = 0.60, 95% CI = 0.44-0.83, p = 0.002) of mortality compared to the normothermia management in an Asian population. Surprisingly, American patients treated with moderate hypothermia showed an increasing mortality (RR = 1.07, 95% CI = 0.83-1.39, p = 0.61). CONCLUSIONS: MHT may be effective in reducing death and unfavourable clinical neurological outcomes, but this finding is not statistically significant, except for decreasing the mortality in Asian patients.

Surgical treatment of traumatic multiple intracranial hematomas.

OBJECTIVE: To summarize our experience with the surgical treatment of traumatic multiple intracranial hematomas (TMIHs) and discuss the surgical indications. METHODS: We analyzed the clinical data of 118 patients with TMIHs who were treated at the West China Hospital in Sichuan University, Chengdu, China between October 2008 and October 2011, including age, gender, cause of injury, diagnosis, treatment, and outcomes. RESULTS: Among the 118 patients, there were 12 patients with different types of hematomas at the same site, 69 with one hematoma type in different compartments, and 37 with different types of hematomas in different compartments. In total, 106 patients had obliteration of basal cisterns, and 34 had a simultaneous midline shift >/=5 mm. Eighty-nine patients underwent single-site surgery, 19 had 2-site surgeries, and 10 patients did not undergo surgery. Based on the Glasgow Outcome Scale 6 months post-injury, 41 patients had favorable outcomes, and 77 had unfavorable outcomes. Basal cisterns obliteration was a strong indicator for surgical treatment. Single- or 2-site surgery was not related to outcome (p=0.234). CONCLUSION: Obliteration of the basal cisterns is a strong indication for surgical treatment of TMIHs. After evacuation of the major hematomas, the remaining hematomas can be treated conservatively. Most patients only require single-site surgical treatment.

A GAD1 inhibitor suppresses osteosarcoma growth through the Wnt/ß-catenin signaling pathway.

Background: As a marker of the GABAergic system, the expression of glutamate decarboxylase 1 (GAD1) is mainly restricted to the central nervous system. Emerging studies have shown that aberrant expression of GAD1 in tumor tissues may promote tumor cell growth. The role of GAD1 in the development of osteosarcoma (OS) remains unclear, so this study sought to investigate the expression status of GAD1 and the effect of its specific inhibitor 3-mercaptopropionic acid (3-MPA) on OS. Methods: The R2 database was used to analyze the relationship between the expression of GAD1 and clinical prognosis in OS patients. Immunohistochemistry was used to compare the expression profile of GAD1 between OS and matched neighboring tissues. The potential antitumor effects of 3-MPA on cell viability, colony formation and the cell cycle were examined. Moreover, the in vivo effect of 3-MPA on tumor growth was investigated using tumor-bearing nude mice. Results: The expression level of GAD1 was aberrantly upregulated in OS tissues, but almost no expression of GAD1 was found in matched neighboring tissues. Western blotting analyses showed upregulation of GAD1 in OS cells compared to human osteoblast cells. In vitro and in vivo, 3-MPA significantly suppressed the growth of OS. Regarding the mechanism, 3-MPA inhibited ß-catenin and cyclin D1 in OS cells, thereby inactivating the Wnt/ß-catenin pathway. Conclusions: OS displays increased expression of the GABAergic neuronal marker GAD1, and 3-MPA significantly reduces OS growth by inhibiting the Wnt/ß-catenin pathway.

RARRES2 is involved in the "lock-and-key" interactions between osteosarcoma stem cells and tumor-associated macrophages.

Osteosarcoma (OS) is a type of tumor. Osteosarcoma stem cells (OSCs) are responsible for drug resistance, recurrence, and immunosuppression in OS. We aimed to determine the heterogeneity of OSCs and the immunosuppression mechanisms underlying the interactions between OSCs and tumor-associated macrophages (TAMs). The cell components, trajectory changes, and cell communication profiles of OS cells were analyzed by transcriptomics at the single-cell level. The intercellular communication patterns of OSCs were verified, and the role of the cell hub genes was revealed. Hub geneS are genes that play important roles in regulating certain biological processes; they are often defined as the genes with the strongest regulatory effect on differentially expressed gene sets. Moreover, various cellular components of the OS microenvironment were identified. Malignant cells were grouped, and OSCs were identified. Further regrouping and communication analysis revealed that the genes in the stemness maintenance and differentiation subgroups were involved in communication with macrophages. Key receptor-ligand pairs and target gene sets for cell communication were obtained. Transcriptome data analysis revealed the key gene RARRES2, which is involved in intercellular communication between OSCs and TAMs. In vitro studies confirmed that macrophages promote RARRES2-mediated stemness maintenance in OSCs via the TAM-secreted cytokine insulin-like growth factor 1. Patient studies confirmed that RARRES2 could be a biomarker of OS. OSCs are highly heterogeneous, and different subgroups are responsible for proliferation and communication with other cells. The IGF-RARRES2 axis plays a key role in maintaining OSC stemness through communication with TAMs.

Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma.

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of ß-catenin in BMSCs.

The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of ß-catenin. Ultimately, the nuclear localization of ß-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.

Epidemiological features of 1 281 patients with head injuries arising from the 2008 Wenchuan earthquake.

OBJECTIVE: To analyze the epidemiological features of patients with head injuries in the 2008 Wenchuan earthquake. METHODS: Medical records of patients with head injuries who were admitted to 14 hospitals in Deyang, Mianyang and Chengdu cities after the earthquake were retrospectively analyzed. The patients'age, gender, cause of injury, diagnosis, and outcome were analyzed retrospectively. RESULTS: A total of 1 281 patients with 807 males and 474 females were included. According to Glasgow Coma Scale score at admission, 1 029 patients presented with mild injury, 161 moderate injury and 91 severe injury. The major cause of injuries (83%) was bruise by collapsed buildings. Open head injuries accounted for 60.8%. A total of 720 patients underwent surgical treatment. Good recovery was achieved in 1 056 patients, moderate disability in 106, severe disability in 71, coma in 29 and death in 19. CONCLUSIONS: In this series, male patients were more than female patients. The main cause of injury was hit by falling objects due to building collapse. Minor and open craniocerebral injuries were most common. The epidemiological features of head injuries in Wenchuan earthquake may be helpful to preparation for future rescue.

Decompressive craniectomy or not: intraoperative experience in 41 patients with severe traumatic brain injury.

OBJECTIVE: To present our experience in using decompressive craniectomy (DC) among severe traumatic brain injury (TBI) patients during operation and to discuss its indication. METHODS: From October 2008 to May 2009, 41 patients aged between 18 and 75 years with severe TBI were included in this study. They underwent DC or non-DC (NDC) according to their intraoperative findings. Postoperative intracranial pressure (ICP), complications, requiring second operation or not and outcomes were observed. RESULTS: Fifteen patients underwent DC and 26 patients did not. The average postoperative ICP of each patient was lower than 20 mm Hg. For patients received DC, 2 had seizures after operation and 1 developed cerebrocele in the follow-up period; only 1 NDC patient had post-traumatic seizures, but none of them had delayed haematoma, cerebrospinal fluid fistula, cerebrocele or infections. At the end of follow-up, 10 patients died, 6 had the GOS of 2, 2 of 3, 9 of 4 and 14 of 5. CONCLUSIONS: DC is necessary to manage fulminant intracranial hypertension or intraoperative brain swelling. If there was not brain swelling after removal of the haematoma and necrotized neural tissues, it is safe to replace skull flap. The intraoperative finding is an important factor to decide whether to perform DC or not.

Case report: Ventriculoperitoneal shunt disconnection resulting in migration of the distal catheter entirely into the abdominal cavity due to seizure.

Ventriculoperitoneal (VP) shunt disconnection, a VP shunt complication, can be caused by several factors. We report the case of a young man who suffered VP shunt disconnection, and whose entire distal catheter migrated into the abdominal cavity due to a seizure. To our knowledge, risk factors for seizures related to shunt disconnection have not been previously evaluated. We report this rare case to highlight the fact that seizures are not negligible in increasing the probability of disconnection and migration of the entire distal catheter into the abdominal cavity, and the standardized treatment of traumatic seizures is extremely important.

Traditional Chinese Medicine Compound-Loaded Materials in Bone Regeneration.

Bone is a dynamic organ that has the ability to repair minor injuries via regeneration. However, large bone defects with limited regeneration are debilitating conditions in patients and cause a substantial clinical burden. Bone tissue engineering (BTE) is an alternative method that mainly involves three factors: scaffolds, biologically active factors, and cells with osteogenic potential. However, active factors such as bone morphogenetic protein-2 (BMP-2) are costly and show an unstable release. Previous studies have shown that compounds of traditional Chinese medicines (TCMs) can effectively promote regeneration of bone defects when administered locally and systemically. However, due to the low bioavailability of these compounds, many recent studies have combined TCM compounds with materials to enhance drug bioavailability and bone regeneration. Hence, the article comprehensively reviewed the local application of TCM compounds to the materials in the bone regeneration in vitro and in vivo. The compounds included icariin, naringin, quercetin, curcumin, berberine, resveratrol, ginsenosides, and salvianolic acids. These findings will contribute to the potential use of TCM compound-loaded materials in BTE.

Early expansive single sided laminoplasty decompression treatment severe traumatic cervical spinal cord injury.

Background: Severe traumatic cervical spinal cord injury (tcSCI) is a disastrous event for patients and families. Maximizing spinal cord function recovery has become the primary therapeutic goal. This study investigated the effect of early extensive posterior decompression on spinal cord function improvement after severe tcSCI. Methods: A retrospective review of 83 consecutive patients who underwent extensive open-door laminoplasty decompression within 24 h after severe tcSCI (American Spinal Injury Association (ASIA) impairment scale (AIS) grade A to C) between 2009 and 2017 at our institution was performed. The patient clinical and demographic data were collected. Neurological functional recovery was evaluated according to the Japanese Orthopaedic Association (JOA) score system, ASIA motor score (AMS) and AIS grade. Results: Among the 83 patients initially included, the baseline AIS grade was A in 12, B in 28, and C in 43. Twenty-three patients (27.7%) had a high cervical injury. Cervical spinal stenosis (CSS) was identified in 37 patients (44.6%). The mean intramedullary lesion length was 59.6 ± 20.4 mm preoperatively and 34.2 ± 13.3 mm postoperatively (p < 0.0001). At the final follow-up visit, an improvement of at least one and two AIS grades was found in 75 (90.4%) and 41 (49.4%) patients, respectively. 24 (64.9%) patients with an improvement of least two AIS grades had CSS. The mean AMS and JOA score were significantly improved at discharge and the final follow-up visit compared with on admission (p < 0.0001). Conclusions: Our results suggest that early expansive laminoplasty decompression may improve neurological outcomes after severe tcSCI, especially in patients with CSS. Larger and prospective controlled studies are needed to validate these findings.

Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration.

Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However, its relation to AS is not clear. In the present study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cells and immune cell infiltration (ICI). We studied gene expression profiles of two cohorts of patients with AS (GSE25101 and GSE41038) derived from the gene expression omnibus database, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to build predictive models for AS based on FRGs, and the ferroptosis level in each sample was assessed via single-sample gene set enrichment analysis. Weighted gene co-expression network and protein-protein interaction network analyses were performed for screening; two key genes, DDIT3 and HSPB1, were identified in patients with AS. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, DDIT3 and HSPB1 were identified as diagnostic markers and potential therapeutic targets for AS. DDIT3 was highly positively correlated with the infiltration levels of various immune cells, while HSPB1 was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, DDIT3 and HSPB1 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy.

Theaflavin-3,3'-Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts.

Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3'-digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models.

Elevated intraspinal pressure drives edema progression after acute compression spinal cord injury in rabbits.

Elevated intraspinal pressure (ISP) following traumatic spinal cord injury (tSCI) can be an important factor for secondary SCI that may result in greater tissue damage and functional deficits. Our present study aimed to investigate the dynamic changes in ISP after different degrees of acute compression SCI in rabbits with closed canals and explore its influence on spinal cord pathophysiology. Closed balloon compression injuries were induced with different inflated volumes (40 µl, 50 µl or no inflation) at the T7/8 level in rabbits. ISP was monitored by a SOPHYSA probe at the epicenter within 7 days post-SCI. Edema progression, spinal cord perfusion and damage severity were evaluated by serial multisequence MRI scans, somatosensory evoked potentials (SEPs) and behavioral scores. Histological and blood spinal cord barrier (BSCB) permeability results were subsequently analyzed. The results showed that the ISP waveforms comprised three peaks, significantly increased after tSCI, peaked at 72 h (21.86 ± 3.13 mmHg) in the moderate group or 48 h (31.71 ± 6.02 mmHg) in the severe group and exhibited "slow elevated and fast decreased" or "fast elevated and slow decreased" dynamic changes in both injured groups. Elevated ISP after injury was correlated with spinal cord perfusion and edema progression, leading to secondary lesion enlargement. The secondary damage aggravation can be visualized by diffusion tensor tractography (DTT). Moreover, the BSCB permeability was significantly increased at the epicenter and rostrocaudal segments at 72 h after SCI; by 14 days, notable permeability was still observed at the caudal segment in the severely injured rabbits. Our results suggest that the ISP of rabbits with closed canals increased after acute compression SCI and exhibited different dynamic change patterns in moderately and severely injured rabbits. Elevated ISP exacerbated spinal cord perfusion, drove edema progression and led to secondary lesion enlargement that was strongly associated with BSCB disruption. For severe tSCI, early intervention targeting elevated ISP may be an indispensable choice to rescue spinal cord function.