HELQ suppresses migration and proliferation of non-small cell lung cancer cells by repairing DNA damage and inducing necrosis.

HELQ plays a key role in DNA damage response and cell-cycle checkpoint regulation. It has been implicated in ovarian and pituitary tumors and may play a role in germ cell maintenance. This study investigated the role of HELQ in lung cancer. The expression of HELQ in patients with non-small-cell lung cancer (NSCLC) was downregulated compared with normal human lungs. Clinical prognostic analysis of Kaplan-Meier plots revealed that patients with NSCLC with low HELQ levels had a reduced overall survival. Further, we found that HELQ depletion enhanced lung cancer cell malignancy. Furthermore, overexpression of HELQ in lung cancer cells reduced cell migration in vitro, while DNA damage repair was inhibited. Both in vitro and in vivo studies have shown that HELQ induces cell death. Mechanistically, we found that cells overexpressing HELQ showed a tendency to induce necrosis. After analyzing the database of HELQ interactors. we found that RIPK3 may interact with it and proved this conclusion by immunoprecipitation. Our findings identified the tumor suppressive role of HELQ in malignant human lung cancer and unraveled a potential therapeutic strategy for cancer treatment through HELQ activation. Moreover, HELQ may also be a predictive biomarker for the clinical predisposition, progression, and prognosis of lung cancer.

Effect of screw tunnels on proximal femur strength after screw removal: A finite element analysis.

BACKGROUND: The presence of screw tunnels in the femoral neck is a problem for patients with proximal femoral fractures after removal of internal fixation. The question of how much does the existence of the screw tunnels affect the strength of the femur and whether the patient needs to be protected with an adjunctive device has been controversial. The objective of this finite element analysis was to determine (1) whether the screw tunnels affects normal weight bearing after removal of internal fixation of a proximal femur fracture, (2) which screw tunnels parameters affect the weight bearing capacity of the entire femur. HYPOTHESIS: The presence of the screw tunnels reduces the load-bearing capacity of the femur, and the arrangement, diameter and wall thickness of the screw tunnels affect the load-bearing capacity of the femur. MATERIALS AND METHODS: Twenty patients who underwent surgical treatment for proximal femur fracture at our hospital were included in the study. Computed tomography (CT) values of the screw tunnel wall in the femur after removal of internal fixations were analysed. Mimics v16.0 and Hypermesh v13.0 software programs were used to generate 3-dimensional (3D) tetrahedral finite element models of the proximal femur with different screw tunnel numbers, diameters, thicknesses, and arrangements. An acetabulum exerting a vertical pressure load of 600N on the femoral head was simulated and the force on various parts of the femur in each model was calculated. RESULTS: There was no difference in the Hounsfield Units of the tunnel walls and cortical bone of the proximal femur (893.48±61.28 vs. 926.34±58.43; p=0.091). In each of the 3D models, the cancellous bone was the first structure to reach maximal stress. The compressive strength of the femur decreased with increasing thickness of the screw tunnel wall and decreased with increasing tunnel diameter. The femoral neck model with the inverted triangle screw tunnel arrangement had the highest compressive strength. DISCUSSION: The femoral neck with screw tunnels can withstand day-to-day stress without special intervention. For femoral neck fractures fixed with cannulated screws, inverted triangle screws are recommended; For a single screw tunnel in the femoral neck, the larger the diameter of the femoral neck internal screw channel, the weaker the load-bearing capacity of the femur. LEVEL OF EVIDENCE: III; well-designed computational non-experimental study.

A Bibliometric Analysis of Publications on Spinal Cord Injury Treatment With Glucocorticoids Using VOSviewer.

Background: Spinal cord injury (SCI) has devastating physical and social consequences for patients. Systemic administration of methylprednisolone (MP) at a higher dosage though can reduce neurological deficits following acute SCI. Still, this treatment regimen is controversial, owing to the apparent dose-related side effects and relatively minor improvement in neurological function. Therefore, this study aimed at the bibliometric analysis of published literature related to SCI treatment, which may lead to future research trends. Methods: The literature published relating to SCI and using glucocorticoids for its treatment between 1982 and 2022 was collected and scanned in the Web of Science collection database using the keywords glucocorticoid, dexamethasone, MP, corticosteroids, and SCI, followed by using VOSviewer for bibliometric analysis of these articles. Results: A total of 1,848 published articles and 7,448 authors on SCI and glucocorticoid usage were identified. The SCI total link strength accounts for 1,341, and MP for 762 has a strong link to neuroprotection and inflammation. The mean citation count for the top 20 most-cited articles was 682 (range: 358-1,828), where most of these were descriptive studies having focused on clinical features. The Journal of Neurotrauma was the highest-ranked journal with 6,010 citations. A total of 69 articles were published by Michael G Fehlings from the University of Toronto with 6,092 citations. The University of Toronto has published 90-related manuscripts with 7,632 citations. In contrast, 800 articles were published in the United States, with 39,633 citations and total link strength of 5,714. The second-ranked country was China, with 241 published articles and 3,403 citations. Conclusions: The research published on applying MP in treating SCI has increased with time. Although the United States has made a significant global contribution to this important field of research, it requires rigorous clinical trials designed to verify the therapeutic role of MP in SCI and its appropriate dosage to find solutions for neurological recovery.

Using Machine Learning Methods to Predict Bone Metastases in Breast Infiltrating Ductal Carcinoma Patients.

Breast cancer (BC) was the most common malignant tumor in women, and breast infiltrating ductal carcinoma (IDC) accounted for about 80% of all BC cases. BC patients who had bone metastases (BM) were more likely to have poor prognosis and bad quality of life, and earlier attention to patients at a high risk of BM was important. This study aimed to develop a predictive model based on machine learning to predict risk of BM in patients with IDC. Six different machine learning algorithms, including Logistic regression (LR), Naive Bayes classifiers (NBC), Decision tree (DT), Random Forest (RF), Gradient Boosting Machine (GBM), and Extreme gradient boosting (XGB), were used to build prediction models. The XGB model offered the best predictive performance among these 6 models in internal and external validation sets (AUC: 0.888, accuracy: 0.803, sensitivity: 0.801, and specificity: 0.837). Finally, an XGB model-based web predictor was developed to predict risk of BM in IDC patients, which may help physicians make personalized clinical decisions and treatment plans for IDC patients.

Identification of a Novel Pyroptosis-Related Gene Signature Indicative of Disease Prognosis and Treatment Response in Skin Cutaneous Melanoma.

Purpose: Pyroptosis plays an important role in the occurrence and progression of many tumors; however, the specific mechanisms involved remain unknown. Here, we construct a pyroptosis-related gene signature that can be used to predict survival prognosis of skin cutaneous melanoma (SKCM) and provide guidance for clinical treatment. Methods: By integrating data from the two databases from the GTEx and TCGA, differentially expressed genes (DEGs) from normal tissues and skin cutaneous tumor tissues were identified. The main signaling pathways and function enrichment of these differential genes were determined. Univariate and multivariate COX regression analysis, and risk score analysis were used to construct a signature to assess its predictive value for overall survival. The mRNA expression of these five genes in melanoma cells was determined by quantitative polymerase chain reaction (qPCR). The pRRophetic algorithm was used to estimate the half-maximal inhibitory concentration (IC50) of chemotherapy drugs in SKCM patients. The expression of multiple immune checkpoint genes also was evaluated. Results: Sixteen DEGs associated with pyroptosis in SKCM and normal skin tissues were identified. Of these, 12 pyroptosis-related DEGs were associated with the prognosis of SKCM. A five-gene signature (GSDMA, GSDMC, IL-18, NLRP6, and AIM2) model was constructed. Patients were divided into high-risk and low-risk groups using the risk scores. Of these, the high-risk group had a worse survival prognosis. There are significant differences in the predicted sensitivity of the high-risk and low-risk groups to chemotherapeutic drugs. In addition, compared with the high-risk group, the low-risk group showed higher expression of PD-1, PDL-1, CTLA-4, LAG-3, and VSIR. Conclusion: In this study, we constructed a novel prognostic pyroptosis-related gene-signature for SKCM. These genes showed good predictive value for patient prognosis and could provide guidance for better treatment of SKCM patients.

Aurora-B knockdown inhibits osteosarcoma metastasis by inducing autophagy via the mTOR/ULK1 pathway.

BACKGROUND: Autophagy plays an essential role in metastasis of malignancies. Although our studies showed that Aurora-B facilitate pulmonary metastasis in OS, the mechanism of Aurora-B kinase on autophagy and metastasis in OS has not been explored. METHODS: Clinical-pathological parameters and follow-up information was collected in OS patients. Immunohistochemical staining was performed to detect Aurora-B and LC3 protein in OS tissues. Short hairpin RNA transfection was used to silence Aurora-B in OS cells. Real-time quantitative PCR (RT-qPCR) was performed to detect Aurora-B mRNA expression in OS cells. Aurora-B and autophagy related protein were measured by Western blot. Transmission electron microscopy and laser scanning confocal microscopy were performed to observe the formation of autophagosomes and autolysosomes. Migratory and invasive ability of OS cells were measured by Wound healing and transwell assays. Orthotopic xenograft model was used to evaluate the effect of autophagy mediated by Aurora-B inhibition on pulmonary metastasis of OS. RESULTS: The elevated expression of Aurora-B protein in OS tissues negatively associated with the overall survival of OS patients. Further investigation has found that Aurora-B expression was negatively correlative with autophagy related protein LC3 in OS patient tissues. Knockdown Aurora-B stimulates autophagy and inhibits migratory and invasive ability of OS cells. Mechanistically, Aurora-B knockdown suppressed the mTOR/ULK1 signaling pathway and reactivation of the mTOR/ULK1 pathway decreased autophagy level. Furthermore, the inhibition effect of silencing Aurora-B on migration and invasion of OS was reversed by chloroquine and mTOR activator in vitro and vivo. CONCLUSIONS: Our results suggest that silencing of Aurora-B stimulate autophagy via decreasing mTOR/ULK1 and result in inhibiting OS metastasis. Targeted Aurora-B/mTOR/ULK1 pathway may be a promising treatment strategy for OS patients.

The risk factors of bone metastases in patients with lung cancer.

The risk factors of bone metastasis in patients with lung cancer are still unclear. Here, a retrospective study including a series of consecutive patients who were diagnosed with lung cancer between January 2005 and November 2016 was carried out. A total of 2021 patients with lung cancer were included in this study and 23.9% of them were found to be bone metastases. For patients with bone metastases, adenocarcinoma (62.1%) was the most common pathological subtype, and rib (62.3%) was the most frequent distant metastatic site, followed by thoracic (53.8%) and lumbar spine (40.4%). The histopathologic type, CA-125 level and the concentration of alkaline phosphatase (ALP) were identified as the independent risk factors for bone metastases in lung cancer (P = 0.002, P = 0.001 and P < 0.001). The sensitivities and specificities of diagnosing bone metastasis by CA-125 were 32.1% and 80.8%, and by ALP were 41.3% and 77.1%, respectively. Thus, the incidence of bone metastases in lung cancer patients was relative high, and physicians should pay attention to the histopathologic type, the serum CA-125 and ALP concentrations when patients were firstly diagnosed with lung cancer for early detecting bone metastases.

Neuron-specific enolase, histopathological types, and age as risk factors for bone metastases in lung cancer.

Lung cancer is a malignant tumor with high metastatic ability and bone is the most common site of distant metastasis of it. However, the independent risk factors for bone metastases of lung cancer remain largely to be elucidated. Here, we conducted a retrospective study to evaluate the correlation between clinical-pathological parameters, serum levels of neuron-specific enolase and CYFRA21-1, and bone metastases in lung cancer patients. The results revealed that patients with bone metastases were younger than those without metastases. Adenocarcinoma was the most frequent type of histopathology in patients with bone metastases. And the incidence of bone metastasis in patients with adenocarcinoma was significantly higher than those with other histopathological subtypes ( p < 0.001). Furthermore, the serum concentration of neuron-specific enolase was significantly higher in patients with bone lesions than those without bone metastases. Multivariate logistic regression analysis showed that patients' age (odds ratio = 1.024, p < 0.001), concentrations of neuron-specific enolase (odds ratio = 1.212, p = 0.004), and histopathological types (odds ratio = 0.995, p = 0.001) were the independent risk factors for bone metastases in patients with lung cancer. Thus, physicians should pay attention to these factors in order to identify bone metastasis earlier while patient was primarily diagnosed as having lung cancer.

The incidences and risk factors related to early dysphagia after anterior cervical spine surgery: A prospective study.

Dysphagia is a common complication following anterior cervical spine surgery (ACSS). The incidences of dysphagia were variable and controversial. The purpose of this study was to determine the incidence of early dysphagia after ACSS with a new scoring system, and to identify the risk factors of it. A prospective study was carried out and patients who underwent ACSS from March 2014 to August 2014 in our hospital were included in this study. A self-designed dysphagia questionnaire was delivered to all of the patients from the first day to the fifth day after ACSS. Perioperative characteristics of patients were recorded, and incidences and risk factors of dysphagia were analyzed. A total of 104 patients who underwent ACSS were included and incidences of dysphagia from the first to the fifth day after ACSS was 87.5%, 79.81%, 62.14%, 50% and 44.23%, respectively. There was a good correlation between the new dysphagia scoring system and Bazaz scoring system (P < 0.001). Operative time and body mass index (BMI) were the risk factors for dysphagia during the first to the second day postoperatively. However, the dC2-C7angle was the main risk factor for dysphagia from the third to the fifth day after surgery. There were comparatively high incidences of early dysphagia after ACSS, which may be ascribed to operative time, BMI and the dC2-C7 angle.