Targeting ferroptosis as a potential strategy to overcome the resistance of cisplatin in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a crucial public health problem, accounting for approximately 2% of all cancers globally and 90% of oral malignancies over the world. Unfortunately, despite the achievements in surgery, radiotherapy, and chemotherapy techniques over the past decades, OSCC patients still low 5-year survival rate. Cisplatin, a platinum-containing drug, serves as one of the first-line chemotherapeutic agents of OSCC. However, the resistance to cisplatin significantly limits the clinical practice and is a crucial factor in tumor recurrence and metastasis after conventional treatments. Ferroptosis is an iron-based form of cell death, which is initiated by the intracellular accumulation of lipid peroxidation and reactive oxygen species (ROS). Interestingly, cisplatin-resistant OSCC cells exhibit lower level of ROS and lipid peroxidation compared to sensitive cells. The reduced ferroptosis in cisplatin resistance cells indicates the potential relationship between cisplatin resistance and ferroptosis, which is proved by recent studies showing that in colorectal cancer cells. However, the modulation pathway of ferroptosis reversing cisplatin resistance in OSCC cells still remains unclear. This article aims to concisely summarize the molecular mechanisms and evaluate the relationship between ferroptosis and cisplatin resistance OSCC cells, thereby providing novel strategies for overcoming cisplatin resistance and developing new therapeutic approaches.

Emerging strategies for nerve repair and regeneration in ischemic stroke: neural stem cell therapy.

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Application of Stand-Alone Oblique Lateral Interbody Fusion in L4-5 Lumbar Diseases.

Lumbar spine diseases often cause lower back pain, lower extremity pain, numbness, and paresthesia. In severe cases, intermittent claudication may occur, affecting the quality of life of patients. Surgery is often required when conservative treatment fails, or when patients' symptoms become unbearable. Surgical treatments include laminectomy and discectomy, as well as interbody fusion. The main purpose of laminectomy and discectomy is to relieve nerve compression; however, recurrence is common due to spinal instability. Interbody fusion improves stability while relieving nerve compression and significantly reduces the risk of recurrence compared to non-fusion surgery. Nonetheless, conventionally posterior intervertebral fusion requires separation of the muscles to expose the operated segment, which causes more trauma to the patient. In contrast, the oblique lateral interbody fusion (OLIF) technique achieves spinal fusion with minimal trauma to the patients and shortens the recovery time. This article introduces procedures of stand-alone OLIF surgery performed in the lumbar spine, providing a reference for other spine surgeons.

Role of lipocalin 2 in stroke.

Stroke is the second leading cause of death worldwide; however, the treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) is a secreted protein, belonging to the lipocalin superfamily, with multiple biological functions in mediating innate immune response, inflammatory response, iron-homeostasis, cell migration and differentiation, energy metabolism, and other processes in the body. LCN2 is expressed at low levels in the brain under normal physiological conditions, but its expression is significantly up-regulated in multiple acute stimulations and chronic pathologies. An up-regulation of LCN2 has been found in the blood/cerebrospinal fluid of patients with ischemic/hemorrhagic stroke, and could serve as a potential biomarker for the prediction of the severity of acute stroke. LCN2 activates reactive astrocytes and microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates, as well as microvascular thrombosis after hemorrhage. In this paper, we review the role of LCN2 in the pathological processes of ischemic stroke; intracerebral hemorrhage; subarachnoid hemorrhage; and stroke-related brain diseases, such as vascular dementia and post-stroke depression, and their underlying mechanisms. We hope that this review will help elucidate the value of LCN2 as a therapeutic target in stroke.

Incidence and risk factors of lumbar plexus injury in patients undergoing oblique lumbar interbody fusion surgery.

PURPOSE: To investigate the incidence and risk factors of lumbar plexus injury (LPI) after oblique lumbar interbody fusion (OLIF) surgery. METHODS: A total of 110 patients who underwent OLIF surgery between January 2017 and January 2021 were retrospectively reviewed. Patients were divided into two groups: the group with LPI (LPI group) and the group without LPI (non-LPI group). The baseline demographic data, surgical variables and radiographic parameters were compared and analyzed between these two groups. RESULTS: Among all participants, 13 (8.5%) had LPI-related symptoms postoperatively (short-term), and 6 (5.5%) did not fully recover after one year (long-term). Statistically, there were no significant differences in the baseline demographic data, surgery duration, intraoperative blood loss, preoperative diagnosis, surgical procedures used and incision length. Compared with the non-LPI group, patients in the LPI group had a narrower OLIF channel space. In LPI group, the anterior edge of left psoas major muscle overpasses the anterior edge of surgical intervertebral disk (IVD) on axial MRI. Logistic regression analysis revealed that narrow OLIF channel space and the anterior edge of left psoas major muscle overpassing the anterior edge of surgical IVD on axial MRI were independently associated with both short-term and long-term LPI. CONCLUSION: Narrow OLIF channel space and the anterior edge of left psoas major muscle overpassing the anterior edge of surgical IVD are significant risk factors of OLIF surgery-related LPI. Surgeons should use preoperative imaging to adequately assess these risk factors to reduce the occurrence of LPI.

Application of the O-arm Intraoperative Imaging System to Assist Anterior Cervical Screw Fixation for Odontoid Fractures.

Odontoid fractures account for a large proportion of cervical spine fractures in the elderly, causing pain in the occiput and the back of the neck and restricting neck movement. Anterior cervical screw fixation is a common surgical procedure to treat odontoid fractures. Due to the special location and complex anatomy of the odontoid, surgeons need to perform intraoperative fluoroscopies repeatedly to ensure correct screw position and avoid damage to the peripheral nerves and vessels of the odontoid. The traditional anterior cervical screw fixation is usually conducted with the assistance of a C-arm. However, compared to the C-arm, an O-arm intraoperative imaging system can provide 3D images during surgery, which improves the accuracy of screw placement. This study retrospectively analyzed patients with anterior cervical odontoid fractures treated in our hospital. The application of the O-arm intraoperative imaging system for assisting screw placement in the treatment of odontoid fractures can reduce intraoperative blood loss, operation time, and trauma to the patients.

DDOST Correlated with Malignancies and Immune Microenvironment in Gliomas.

Among the most common types of brain tumor, gliomas are the most aggressive and have the poorest prognosis. Dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST) encodes a component of the oligosaccharide transferase complex and is related to the N-glycosylation of proteins. The role of DDOST in gliomas, however, is not yet known. First, we performed a pan cancer analysis of DDOST in the TCGA cohort. The expression of DDOST was compared between glioma and normal brain tissues in the GEO and Chinese Glioma Genome Atlas (CGGA) databases. In order to explore the role of DDOST in glioma, we analyze the impact of DDOST on the prognosis of glioma patients, with the CGGA 325 dataset as a test set and the CGGA 693 dataset as a validation set. Immunohistochemistry was performed on tissue microarrays to examine whether DDOST has an impact on glioma patient survival. Next, using single-cell sequencing analysis, GSEA, immune infiltration analysis, and mutation analysis, we explored how DDOST affected the glioma tumor microenvironment. Finally, we evaluated the clinical significance of DDOST for glioma treatment by constructing nomograms and decision curve analysis (DCA) curves. We found that DDOST was overexpressed in patients with high grade, IDH wild type, 1p19q non-codel and MGMT un-methylated, which was associated with poor prognosis. Patients with high levels of DDOST, regardless of their clinical characteristics, had a worse prognosis. Immunohistochemical analysis confirmed the results of the above bioinformatics analysis. Mechanistic analysis revealed that DDOST was closely associated with the glioma microenvironment and negatively related to tumor-infiltrating B cells and CD4+ T cells and positively related to CAFs and tumor-associated macrophages. In conclusion, these findings suggested that DDOST mediated the immunosuppressive microenvironment of gliomas and could be an important biomarker in diagnosing and treating gliomas.

Risk Factors of Total Blood Loss and Hidden Blood Loss in Patients with Adolescent Idiopathic Scoliosis: A Retrospective Study.

Objectives: To investigate the risk factors of total blood loss (TBL) and hidden blood loss (HBL) in adolescent idiopathic scoliosis (AIS) patients undergoing posterior orthopedic surgery. Methods: The AIS patients who visited department of spine surgery between January 2015 and December 2020 were retrospectively reviewed. Those with a history of posterior orthopedic surgery for AIS were identified, and their clinical data were collected. Gross formula was used to calculate the TBL and HBL. SPSS 20.0 was used for statistical analysis. The potential risk factors of TBL and HBL were assessed by independent t-test or univariate analysis. The risk factors of TBL and HBL were determined by multiple linear regression. Results: A total of 114 patients were included in this study. Operative time (P < 0.001), postoperative platelets (PLT) (P = 0.001), the number of surgical fixation segments (P < 0.001), implanted screws (P < 0.001), hospital stay (P = 0.006), type of scoliosis (P < 0.001), and correction angle of scoliosis (P = 0.063) were the potential risk factors of TBL. Operative time (P < 0.000), postoperative PLT (P = 0.095), the number of surgical fixation segments (P < 0.001), implanted screws (P < 0.001), type of scoliosis (P < 0.001), correction angle of scoliosis (P = 0.073), and total blood volume (P = 0.098) were the potential risk factors of HBL. Multiple linear regression analysis showed that operative time (P = 0.003) and the number of surgical fixation segments (P = 0.014) were risk factors of TBL, while the number of surgical fixation segments (P = 0.004) was a risk factor of HBL. Conclusions: In AIS patients undergoing posterior internal fixation surgery, the operative time and the number of surgical fixation segments are risk factors of TBL, and the number of surgical fixation segments is a risk factor of HBL. Surgeons need to consider these factors when making surgical strategies for AIS patients.

Correlation Analysis between Tamoxifen and Lumbar Intervertebral Disc Degeneration: A Retrospective Case-Control Study.

Objectives: To investigate the correlation between tamoxifen (TAM) and lumbar intervertebral disc (IVD) degeneration (IVDD). Methods: The patients who visited the department of spine surgery from January 2015 to December 2020 were retrospectively reviewed. Those with a history of breast cancer surgery were identified and their data were collected. These data included patients' age, body mass index (BMI), menstrual history, postoperative history, drug treatment plan, and imaging data. The participants were divided into the TAM group and the non-TAM group. Lumbar IVDD was assessed by lumbar lordosis (LL), vertebral CT density, lumbar disc height index (DHI), Modic changes, and modified Pfirrmann grading score. SPSS 20 was used for statistical analysis. Results: A total of 75 patients were included in this study, 46 patients in the TAM group and 29 patients in the non-TAM group. No significant differences were present in age, BMI, postoperative history, LL, and vertebral CT density between the two groups. The DHI of L1/2 and L2/3 in the TAM group was lower compared to the non-TAM group (P=0.038 and P=0.034, respectively), while comparisons regarding the DHI of L3/4, L4/5, and L5/S1, and the average DHI between TAM and non-TAM groups were not significant. The modified Pfirrmann grading scores of the L1/2 and L2/3 IVDs in the TAM group were higher than those in the non-TAM group (P=0.004 and P=0.025, respectively). Comparisons of L3/4, L4/5, and L5/S1 between the two groups were not significant. The comparisons regarding the occurrence of Modic changes did not show a significant difference between the TAM and non-TAM groups. Conclusions: This study indicates that there might be some positive correlation between TAM use and lumbar IVDD. In particular, the degeneration of L1/2 and L2/3 has shown a correlation with TAM use.

Anemia was associated with multilevel lumbar disc degeneration in patients with low back pain: a single-center retrospective study.

PURPOSE: It has not been determined which factors were related to multilevel lumbar disc degeneration (MLDD). The objective of this study was to determine the prevalence of MLDD among symptomatic patients using the magnetic resonance imaging method. The study also aimed to clarify the associations between MLDD and suspected risk factors through a multivariate model. METHODS: A total of 530 young and middle-aged patients, suffered from low back pain were retrospectively assessed by 2 independent observers, who used sagittal T2-weighted MR imaging. Subjects were divided into two groups, MLDD group and non-MLDD group, according to the number of degenerated discs. Demographic and radiological data included age, gender, weight, height, body mass index, smoking status, alcohol drinking, lumbar lordosis, presence of hypertension (HT), diabetes mellitus and anemia. RESULTS: There were 309 men and 221 women with an average age of 37.5 ± 8.5 years. In general, 37.7% of patients were diagnosed with disc degeneration (DD) at more than two levels. Triple level DD was the most common pattern and was more prevalent in women (p <0.05). Using multivariate analyses, age (odds ratio [OR]: 1.14; 95% confidence interval [CI] 1.11-1.18; p <0.001), hypertension (OR: 2.67; 95% CI 1.38-5.16; p = 0.03) and anemia (OR: 3.84; 95% CI 2.03-7.28; p <0.001) were significantly associated with MLDD. CONCLUSION: Despite the young age of this cohort, MLDD is common among patients with low back pain. A significant independent association exists between age, HT, anemia and multilevel disc degeneration in the lumbar region.

Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke.

Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed. Hypoxia inducible factor-1α (HIF-1α) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia/ischemia. It plays an extensive role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, and blood brain barrier regulation. In addition, the spatiotemporal expression profile of HIF-1α in the brain shifts with the progression of ischemic stroke; this has led to contradictory findings regarding its function in previous studies. Therefore, unveiling the Janus face of HIF-1α and its target genes in different type of cells and exploring the role of HIF-1α in inflammatory responses after ischemia is of great importance for revealing the pathogenesis and identifying new therapeutic targets for ischemic stroke. Herein, we provide a succinct overview of the current approaches targeting HIF-1α and summarize novel findings concerning HIF-1α regulation in different types of cells within neurovascular units, including neurons, endothelial cells, astrocytes, and microglia, during the different stages of ischemic stroke. The current representative translational approaches focused on neuroprotection by targeting HIF-1α are also discussed.

Quantitative proteomics reveals arsenic attenuates stem-loop binding protein stability via a chaperone complex containing heat shock proteins and ERp44.

Arsenic pollution impacts health of millions of people in the world. Inorganic arsenic is a carcinogenic agent in skin and lung cancers. The stem-loop binding protein (SLBP) binds to the stem-loop of the canonical histone mRNA and regulates its metabolism during cell cycle. Our previous work has shown arsenic induces ubiquitin-proteasome dependent degradation of SLBP and contributes to lung cancer. In this study, we established the first comprehensive SLBP interaction network by affinity purification-mass spectrometry (AP-MS) analysis, and further demonstrated arsenic enhanced the association between SLBP and a crucial chaperone complex containing heat shock proteins (HSPs) and ERp44. Strikingly, knockdown of these proteins markedly rescued the protein level of SLBP under arsenic exposure conditions, and abolished the increasing migration capacity of BEAS-2B cells induced by arsenic. Taken together, our study provides a potential new mechanism that a chaperone complex containing HSPs and ERp44 attenuates the stability of SLBP under both normal and arsenic exposure conditions, which could be essential for arsenic-induced high cell migration.

Global Phosphoproteomic Analysis Reveals Significant Metabolic Reprogramming in the Termination of Liver Regeneration in Mice.

Phosphorylation is crucial in regulating various biological processes. However, comprehensive phosphoproteomic profiling in the termination of liver regeneration (LR) is still missing. Here, we used Tandem Mass Tag (TMT) labeling coupled with phosphopeptide enrichment and two-dimensional (2D) liquid chromatography-mass spectrometry (LC-MS)/MS analysis to establish a global phosphoproteomic map in the liver of mice at day 5 after partial hepatectomy (PH). Altogether, 9731 phosphosites from 3443 proteins were identified and 7802 phosphosites from 2980 proteins were quantified. Motif analysis of the identified phosphosites revealed a diverse array of consensus sequences, suggesting that multiple kinase families including ERK/MAPK, PKA/PKC, CaMK-II, CKII, and CDK may be involved in the termination of LR. Functional clustering analysis of proteins with dysregulated phosphosites showed that they mainly participate in metabolic pathways, DNA replication, and tight junction. More importantly, the deletion of PP2Acα in the liver remarkably changes the overall phosphorylation profile, indicating its critical role in regulating the termination of LR. Finally, several differentially phosphorylated sites were validated by co-immunoprecipitation and Western blot. Taken together, our data unravel the first comprehensive phosphoproteomic map in the termination of LR in mice, which greatly expands our knowledge in the complicated regulation of this process and provides new directions for the treatment of liver cancer using liver resection.

Prevalence and risk factors of axial neck pain in patients undergoing multilevel anterior cervical decompression with fusion surgery.

OBJECTIVES: The aim of this study was to explore the prevalence and risk factors for axial neck pain in patients undergoing multilevel anterior cervical decompression with fusion surgery. METHODS: In this study, 88 patients, who underwent multilevel anterior cervical decompression with fusion surgery from January 2012 to January 2017, were retrospectively reviewed. Based on the postoperative axial neck pain, the patients were classified into two groups: axial pain group and no axial pain group. The patients were followed up 3 weeks, 3 months, and 1 year after cervical anterior surgery for the early- and long-term clinical evaluation. The possible effect factors included demographic variables (age, sex, BMI, smoking, drinking, heart disease, hypertension, diabetes, preoperative kyphosis, preoperative axial neck pain, preoperative JOA scores, and ODI) and surgery-related variables (surgical option, vertebral lesions, spinal canal stenosis rate, superior fusion segment, presence of intramedullary high signal intensity). RESULTS: The prevalence of axial neck pain was 27.3% (24 cases of 88). Our results showed that preoperative axial neck pain (62% vs 23%, P < 0.001) and preoperative kyphosis (42% vs 21.9%, P < 0.001) were risk factors for axial pain after multilevel anterior cervical surgery. Additionally, for patients with preoperative cervical kyphosis, compared to no axial pain group, the axial neck group was significantly more likely to exist a higher preoperative angle of C2-7 (13.31 ± 2.33 vs 7.33 ± 2.56, P < 0.001) and a higher correction range for kyphosis (20.24 ± 4.12 vs 12.34 ± 3.12, P < 0.001). However, for all the patients with postoperative axial symptoms, the improvement rate of axial pain was significantly higher for patients without cervical kyphosis at the early-term follow-up (3 weeks) (P = 0.032), no significant differences were found at the medium-term (P = 0.554) and long-term follow-up (P = 0.902), and improvements of clinical symptom have no obvious difference at the last follow-up. CONCLUSIONS: Overall, preoperative axial neck pain and kyphosis could predict axial neck pain for patients undergoing multilevel anterior cervical decompression with fusion surgery, and recovery of cervical kyphosis may contribute to the long-term recovery of neural function, but may also suffer from risk of short-term axial pain, which could be reduced through moderate cervical curvature recovery.