Associations between weight-adjusted-waist index and telomere length: Results from NHANES: An observational study.

Previous studies have demonstrated the connection between obesity and telomere length. A recently devised metric for determining obesity, the weight-adjusted-waist index (WWI), offers a distinct advantage in predicting fat and lean mass by depicting weight-independent abdominal adiposity. This article presents the results of the inaugural study on the relationship between WWI and telomere length in adult populations. The cross-sectional investigation analyzed data from 3479 participants from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2000. To inspect linear and nonlinear correlations, we adopted weighted multiple logistic regression analysis and smooth curve fit, respectively. In addition, threshold effects and subgroup analyses were accomplished. In the fully adapted model, a significant adverse association of WWI with telomere length was detected [ß = -0.02, 95% CI: (-0.03, -0.00), P value = 0.01]. The adverse correlation remained consistent across all subcategories. We also discovered an inverted U-shaped curve linking WWI and telomere length, with a conspicuous inflection point of 10.07 cm/√kg. For the first time, our research demonstrated strong links between WWI and telomere length. The inflection point suggests that controlling WWI within an optimum range might be essential for aging and health.

Comparison between combined ultrasounds and magnetic resonance imaging in the differentiation of benign and malignant breast lesions: a cross-sectional study.

AIM: To explore the performance of single or combined ultrasound (US) in diagnosing malignant breast lesions, and then compare the results with a magnetic resonance imaging (MRI) aspect. MATERIAL AND METHODS: Patients' demographics, tumor markers, and imaging examination were collected. Diagnostic models based on B-mode, color Doppler ultrasounds (CDU), strain elastography (SE), MRI, B-mode US + CDU, B-mode US + SE, and B-mode US + CDU + SE were developed using logistic regression analysis. The performance was assessed using the area under the curve (AUC) with 95% confidence intervals (CIs). Performance of MRI and B-mode US + CDU was compared using DeLong analysis. RESULTS: For single imaging modality, MRI showed the best performance, with AUC of 0.938 (95%CI: 0.888-0.988). For combined US modalities, combination of B-mode US and CDU had the best performance, with AUC of 0.948 (95%CI: 0.877-1.000). There was no significant difference in the diagnostic performance between the combination of B-mode US and CDU and MRI (p>0.05). CONCLUSIONS: Our study found the performance of B-mode + CDU was comparable to MRI. Our findings suggested that the combination of B-mode US and CDU was recommended to diagnose malignant breast lesions in order to save time and expense and provide guidance to make decisions for a biopsy.

Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma.

BACKGROUND: Copper and copper-binding proteins are key components of tumor progression as they play important roles in tumor invasion and migration, but their associations in gliomas remain unclear. METHODS: Transcriptomic datasets of glioblastoma, low-grade glioma, and normal brain cortex were derived from the TCGA and GTEX databases. Differentially expressed genes (DEGs) of copper-binding proteins were screened and used to construct a prognostic model based on COX and LASSO regression, which was further validated by the CGGA datasets. The expressions of risk-model genes were selectively confirmed via anatomic feature-based expression analysis and immunohistochemistry. The risk score was stratified by age, gender, WHO grade, IDH1 mutation, MGMT promoter methylation, and 1p/19q codeletion status, and a nomogram was constructed and validated. RESULTS: A total of 21 DEGs of copper-binding proteins were identified and a six-gene risk-score model was constructed, consisting of ANG, F5, IL1A, LOXL1, LOXL2, and STEAP3, which accurately predicted 1-, 3-, and 5-year overall survival rates, with the AUC values of 0.87, 0.88, and 0.82, respectively. The high-risk group had a significantly shorter OS (p < 0.0001) and was associated with old age, wild-type IDH1, a high WHO grade, an unmethylated MGMT promoter, and 1p/19q non-codeletion and had higher levels of immune cell infiltration, cancer-immunity suppressor, and immune checkpoint gene expression as well as a higher TMB. CONCLUSIONS: The model based on the genes of copper-binding proteins could contribute to prognosis prediction and provide potential targets against gliomas.

Assessment of 13 essential and toxic trace elements in tumor and peritumoral brain tissues from human glioblastoma.

Trace elements within the brain are important for proper neurological function, but their imbalance has been rarely investigated in glioblastoma. This study enrolled a total of 14 patients with glioblastoma, and the tumor and peritumoral brain tissues were collected while undergoing surgery. The concentrations of Mg, Ca, Cr, Mn, Fe, Co, Cu, Zn, Se, As, Cd, Tl and Pb were determined using a well-evaluated ICP-MS method. The Cu- and Cd-binding proteomes were further analyzed using the anatomic transcriptional atlas from Ivy GAP. Histological evaluation was based on rubeanic acid staining and immunohistochemistry, respectively. The 13 trace element concentrations were obtained, and the highest were Ca, Mn, Fe, Zn and Cu, ranging from a few to dozens of ug/g. Correlation analysis suggested the existence of two intra-correlated clusters: essential metals (Cu-Ca-Zn-Mg) and heavy metals (Pb-As-Cd-Tl-Co-Cr-Mn). Compared to the tumor samples, significantly higher levels of Cu and Cd were observed in the peritumoral region. Further analysis of the Cu- and Cd-binding proteins from the anatomic view suggested that DBH and NOS1 were obviously increased in the leading edge than the central tumor region. Consistent with the above findings, histological evaluation of Cu and DBH further confirmed more copper and DBH expressions in the peritumoral area compared to the tumor core. Trace elements differ in tumor and peritumoral brain zone in glioblastoma, which may associate with tumor angiogenesis.

The prognostic value and immune landscaps of m6A/m5C-related lncRNAs signature in the low grade glioma.

BACKGROUND: N6-methyladenosine (m6A) and 5-methylcytosine (m5C) are the main RNA methylation modifications involved in the oncogenesis of cancer. However, it remains obscure whether m6A/m5C-related long non-coding RNAs (lncRNAs) affect the development and progression of low grade gliomas (LGG). METHODS: We summarized 926 LGG tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas and Chinese Glioma Genome Atlas. 105 normal brain samples with RNA-seq data from the Genotype Tissue Expression project were collected for control. We obtained a molecular classification cluster from the expression pattern of sreened lncRNAs. The least absolute shrinkage and selection operator Cox regression was employed to construct a m6A/m5C-related lncRNAs prognostic signature of LGG. In vitro experiments were employed to validate the biological functions of lncRNAs in our risk model. RESULTS: The expression pattern of 14 sreened highly correlated lncRNAs could cluster samples into two groups, in which various clinicopathological features and the tumor immune microenvironment were significantly distinct. The survival time of cluster 1 was significantly reduced compared with cluster 2. This prognostic signature is based on 8 m6A/m5C-related lncRNAs (GDNF-AS1, HOXA-AS3, LINC00346, LINC00664, LINC00665, MIR155HG, NEAT1, RHPN1-AS1). Patients in the high-risk group harbored shorter survival times. Immunity microenvironment analysis showed B cells, CD4 + T cells, macrophages, and myeloid-derived DC cells were significantly increased in the high-risk group. Patients in high-risk group had the worse overall survival time regardless of followed TMZ therapy or radiotherapy. All observed results from the TCGA-LGG cohort could be validated in CGGA cohort. Afterwards, LINC00664 was found to promote cell viability, invasion and migration ability of glioma cells in vitro. CONCLUSION: Our study elucidated a prognostic prediction model of LGG by 8 m6A/m5C methylated lncRNAs and a critical lncRNA regulation function involved in LGG progression. High-risk patients have shorter survival times and a pro-tumor immune microenvironment.

A Comparison of the Safety, Efficacy, and Accuracy of Frame-Based versus Remebot Robot-Assisted Stereotactic Systems for Biopsy of Brainstem Tumors.

BACKGROUND: Brainstem tumors are rare and extremely heterogeneous and present significant challenges in surgical treatment. Thus, biopsies often set the foundation for the diagnosis of brainstem tumors. Multimodal, image-guided, robot-assisted frameless stereotactic biopsies are increasingly popular in neurosurgery centers. This study aimed to compare the safety, efficacy, and duration of the Remebot robot-assisted (Remebot) frameless brainstem tumor biopsy versus those of frame-based stereotactic biopsy. METHOD: A retrospective analysis of 33 patients with brainstem tumors who underwent stereotactic brainstem biopsies in the department of neurosurgery from January 2016 to January 2021 was conducted. The patients were divided into two groups: the Remebot group (n = 22) and the frame-based group (n = 11). The clinical characteristics, trajectory strategy, duration of procedure, diagnostic yielding, histopathological diagnosis, and postoperative complications were retrospectively analyzed and compared between the groups. RESULTS: More pediatric patients performed Remebot frameless brainstem tumor biopsy than frame-based biopsy, with a mean age of 17.3 ± 18.7 vs. 32.8 ± 17.1 (p = 0.027). The diagnostic yield had no significant difference in the two groups, with the diagnostic yield of frame-based biopsy and Remebot frameless brain biopsy being 90.9% and 95.5%, respectively. The time of the total process was 124.5 min for the frame-based biopsy and 84.7 min for the Remebot frameless brain biopsy (p < 0.001). There were no significant differences with respect to the occurrence of complication or the duration of the operation between the two groups. CONCLUSION: Remebot frameless stereotactic brainstem biopsy is as safe and efficacious as frame-based stereotactic biopsy. However, Remebot frameless biopsy can reduce the total duration of the procedure and has better application in young pediatric patients. Remebot frameless stereotactic biopsies can be a better option towards the safe and efficient treatment of brainstem tumors.

DIA-MS Based Proteomics Combined with RNA-Seq Data to Unveil the Mitochondrial Dysfunction in Human Glioblastoma.

Mitochondrial dysfunctions underlie the pathogenesis in glioblastoma multiforme (GBM). Comprehensive proteomic profiling of mitochondria-specific changes in human GBM is still insufficient. This study carried out a DIA-MS based proteomic analysis on the mitochondria isolated from human primary GBM and peritumoral tissue (as paired control), and further compared those findings with the transcriptomic datasets. A total of 538 mitochondrion-specific proteins were rigorously confirmed, among which 190 differentially expressed proteins were identified. Co-regulations of the mitochondrial dysfunction pathway networks were observed, including significant up-regulations of mitochondrial translation and apoptosis, as well as down-regulations of OXPHOS and mitochondrial dynamics. Proteins related to FA, AA metabolism and ROS also showed significant variations. Most of these alterations were consistent in trend when compared the proteomics findings with the RNA-Seq datasets, while the changes at protein levels appeared to be more dramatic. Potentially key proteins in GBM were identified, including up-regulated pro-apoptotic protein CASP3, BAX, fatty acid oxidation enzymes CPT1A, CPT2, ACADM, serine-glycine enzymes SHMT2, GATM, ROS-related protein SOD2, GPX1, and CAT; and down-regulated dynamin-related protein MFN1, MFN2, OPA1, and OXPHOS components; and also several differentially expressed ALDH isoforms. This study systematically profiled the mitochondrial dysfunctions by combining proteomic findings and mRNA datasets, which would be a valuable resource to the community for further thorough analyses.

The Dual Role of PDCD10 in Cancers: A Promising Therapeutic Target.

Programmed cell death 10 (PDCD10) was initially considered as a protein associated with apoptosis. However, recent studies showed that PDCD10 is actually an adaptor protein. By interacting with multiple molecules, PDCD10 participates in various physiological processes, such as cell survival, migration, cell differentiation, vesicle trafficking, cellular senescence, neurovascular development, and gonadogenesis. Moreover, over the past few decades, accumulating evidence has demonstrated that the aberrant expression or mutation of PDCD10 is extremely common in various pathological processes, especially in cancers. The dysfunction of PDCD10 has been strongly implicated in oncogenesis and tumor progression. However, the updated data seem to indicate that PDCD10 has a dual role (either pro- or anti-tumor effects) in various cancer types, depending on cell/tissue specificity with different cellular interactors. In this review, we aimed to summarize the knowledge of the dual role of PDCD10 in cancers with a special focus on its cellular function and potential molecular mechanism. With these efforts, we hoped to provide new insight into the future development and application of PDCD10 as a clinical therapeutic target in cancers.

Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells.

Glioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alternative RNA splicing. The acidic pH in the core switches before messenger RNA splicing of the ribosomal gene RPL22L1 towards the RPL22L1b isoform. This allows cells to survive acidosis, increases stemness and correlates with worse patient outcome. Mechanistically, RPL22L1b promotes RNA splicing by interacting with lncMALAT1 in the nucleus and inducing its degradation. Contrarily, in the tumour edge region, RPL22L1a interacts with ribosomes in the cytoplasm and upregulates the translation of multiple messenger RNAs including TP53. We found that the RPL22L1 isoform switch is regulated by SRSF4 and identified a compound that inhibits this process and decreases tumour growth. These findings demonstrate how distinct GBM cell populations arise during tumour growth. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy.

[The value of ACR-TIRADS and C-TIRADS in the diagnosis of nodular Hashimoto thyroiditis and papillary thyroid carcinoma with Hashimoto thyroiditis].

Objective:To explore the diagnostic value of American Society of Radiology Thyroid Imaging Reporting and Data System（ACR-TIRADS） and Chinese Thyroid Nodule Ultrasound Malignant Risk Stratification（C-TIRADS） in nodular Hashimoto thyroiditis and papillary thyroid carcinoma with Hashimoto thyroiditis. Methods:This retrospective analysis included 144 patients（204 thyroid nodules） accompanied by nodular Hashimoto thyroiditis or papillary thyroid carcinoma under the background of Hashimoto thyroiditis confirmed by surgical pathology examination in the First Affiliated Hospital of Hebei North University from August 2018 to May 2021, all nodules were examined by ultrasound, and 204 nodules were scored and graded according to the classification standards of ACR-TIRADS and C-TIRADS. The surgical pathological results were the gold standard. The receiver operating characteristic curve of ACR-TIRADS and C-TIRADS was constructed to evaluate and compare the diagnostic performance of the two guideline. Results:①Ultrasound feature results showed that nodular Hashimoto thyroiditis and Papillary thyroid carcinoma had statistically significant differences in the location, echogenicity, calcifications and margins（P<0.001）, but there is no significant difference in structure and aspect ratio between the two kinds of nodular（P=0.141, P=0.240）; nodular Hashimoto thyroiditis were mostly absent focal echogenicity and hyperechogenicity, while papillary thyroid carcinoma was mostly manifested as focal echogenicity and extrinsic thyroid invasion. ②The sensitivity and negative predictive value of C-TIRADS were 91.7% and 83.1%, respectively, which were higher than those of ACR-TIRADS, and the difference was statistically significant（P=0.021, P=0.013）; The specificity and positive predictive value of C-TIRADS T were 98.3% and 99.2%, both of which were slightly higher than ACR-TIRADS, althought the difference was not statistically significant（P=0.157, P=0.062）. The area under the curve of the ACR-TIRADS and C-TIRADS were 0.806 and 0.941, respectively, and the difference was statistically significant（P=0.031）. ③The unnecessary FNAB rate of C-TIRADS was 10.3%, which was lower than ACR-TIRADS. Conclusion:C-TI-RADS has a better diagnostic value of nodular Hashimoto thyroiditis and thyroid papillary carcinoma under the background of Hashimoto thyroiditis, which is helpful for clinical evaluation of such nodules.