METTL16 Inhibits the Malignant Progression of Epithelial Ovarian Cancer through the lncRNA MALAT1/ß-Catenin Axis.

Epithelial ovarian cancer (EOC) ranks third in the incidence of gynecological malignancies. m6A methylation as RNA modification plays a crucial role in the evolution, migration, and invasion of various tumors. However, the role of m6A methylation in ovarian cancer (OC) only recently has begun to be appreciated. Therefore, we used various bioinformatic methods to screen the public GEO datasets of epithelial ovarian cancer (EOC) for m6A methylation-related regulators. We identified methyltransferase 16 (METTL16) that was dramatically downregulated in EOC as such a regulator. We also identified metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a known target lncRNA of METTL16, in these five GEO datasets. RT-qPCR and immunohistochemical staining confirmed that compared with the normal ovarian tissues and cells, METTL16 was significantly downregulated, while lncRNA MALAT1 was significantly upregulated, in 30 EOC tissues of our own validation cohorts and EOC cell lines, revealing a negative correlation between METTL16 and lncRNA MALAT1. Moreover, our analysis unveiled a correlation between downregulated METTL16 and the known adverse prognostic factors of EOC patients in our own cohorts. The CCK-8, EdU, scratch wound healing, and transwell invasion assays revealed that METTL16 significantly suppressed the proliferating, migrating, and invading abilities of OC cells. The inhibitory effects of METTL16 on the in vivo tumor growth of EOC cells were measured by subcutaneous tumor formation assay in mice. Furthermore, the RIP, RNA stability assay, western blotting, and cytoimmunofluorescence staining showed that METTL16 hindered the growth of EOC cells through promoting the degradation of MALAT1 by binding that, in turn, upregulates ß-catenin protein and promotes nuclear transport of ß-catenin protein in EOC cells. This study suggests that METTL16 acts as a tumor suppressor gene of EOC by achieving its inhibitory function on the malignant progression of EOC through the METTL16/MALAT1/ß-catenin axis that are new targets for EOC diagnosis and therapy.

Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration.

Lung cancer maintains high morbidity and mortality rate globally despite significant advancements in diagnosis and treatment in the era of precision medicine. Pathological analysis of tumor tissue, the current gold standard for lung cancer diagnosis, is intrusive and intrinsically confined to evaluating the limited amount of tissues that could be physically extracted. However, tissue biopsy has several limitations, including the invasiveness of the procedure and difficulty in obtaining samples for patients at advanced stages., there Additionally,has been no major breakthrough in tumor biomarkers with high specificity and sensitivity, particularly for early-stage lung cancer. Liquid biopsy has been considered a feasible auxiliary tool for tearly dianosis, evaluating treatment responses and monitoring prognosis of lung cancer. Circulating tumor DNA (ctDNA), an ideal biomarker of liquid biopsy, has emerged as one of the most reliable tools for monitoring tumor processes at molecular levels. Herein, this review focuses on tumor heterogeneity to elucidate the superiority of liquid biopsy and retrospectively discussdeciphersolution. We systematically elaborate ctDNA biological characteristics, introduce methods for ctDNA detection, and discuss the current role of plasma ctDNA in lung cancer management. Finally, we summarize the drawbacks of ctDNA analysis and highlight its potential clinical application in lung cancer.

Clinical Significance of Methyltransferase-like 16 Expression in Epithelial Ovarian Cancer.

OBJECTIVE: To detect methyltransferase-like (METTL) 16 expression in epithelial ovarian cancer (EOC) by immunohistochemistry (IHC), and its relationship with clinicohistopathological parameters and prognosis. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Gynaecology and Pathology, The First Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), from February to June 2022. METHODOLOGY: METTL16 expression in 115 EOC patients was evaluated by IHC. According to the immunoreactive score (IRS), scores <6 represented low expressions and ≥6 high expressions. Clinicopathologic data and follow-up information were collected for statistical evaluation. RESULTS: METTL16 expression decreased in EOC (p = 0.001) and affected the poor prognosis of EOC patients. Low METTL16 patients expression had significantly higher frequencies of advanced FIGO stage, low grade, more lymph node metastasis, high CA125 levels, bilateral disease, distant metastasis, and high frequency of neural/vascular invasion compared to high METTL16 patients (p ≤0.001, <0.001, <0.001, 0.017, 0.027, <0.001, and 0.010, respectively). The survival analysis showed that the overall survival (p <0.0001) as well as the disease-free survival (p <0.0001) were remarkably shorter in low METTL16 patients compared to high METTL16 patients, suggesting worse survival. CONCLUSION: There was a clear association between the expression of METTL16, poor prognostic factors, and lower survival of EOC patients, suggesting that it might exert a vital effect on the malignant progression / prognosis of EOC. KEY WORDS: Epithelial ovarian cancer (EOC), METTL16, Immunohistochemistry, Prognosis.

Emerging Role of Noncoding RNAs in EGFR TKI-Resistant Lung Cancer.

Lung cancer accounts for the majority of malignancy-related mortalities worldwide. The introduction of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and significantly improved the overall survival (OS) of lung cancer. Nevertheless, almost all EGFR-mutant patients invariably acquire TKI resistance. Accumulating evidence has indicated that noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), have a central role in the tumorigenesis and progression of lung cancer by regulating crucial signaling pathways, providing a new approach for exploring the underlying mechanisms of EGFR-TKI resistance. Therefore, this review comprehensively describes the dysregulation of ncRNAs in EGFR TKI-resistant lung cancer and its underlying mechanisms. We also underscore the clinical application of ncRNAs as prognostic, predictive and therapeutic biomarkers for EGFR TKI-resistant lung cancer. Furthermore, the barriers that need to be overcome to translate the basic findings of ncRNAs into clinical practice are discussed.

Comparison between open reduction with internal fixation to circular external fixation for tibial plateau fractures: A systematic review and meta-analysis.

Peer-reviewed published studies on tibial plateau fractures treated with either open reduction with internal fixation (ORIF) or circular external fixation were reviewed to compare functional, radiological outcomes, postoperative complications, and reoperation rates between the two methods. A systematic search of various databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until June 2019 was performed. 17 studies with 1168 participants were included in the review. Most of the studies (76%) were retrospective in nature and had low or unclear bias risks. Incidence of total infection (Odds ratio [OR], 2.58; 95% CI, 1.33-5.02) and malunions (OR, 2.56; 95% CI, 1.12-5.84) were higher and length of hospital stay was shorter in patients treated with circular external fixator (Mean difference [MD], -6.1; 95% CI, -11.1--1.19). There were no differences in the incidence of secondary osteoarthritis (OR, 1.49; 95% CI, 0.92-2.42), range of motion (MD, 2.28; 95% CI, -11.27-15.82) non-union (OR, 1.44; 95% CI, 0.14-14.27) and reoperation rates (OR, 1.84; 95% CI, 0.90-3.78) between the two groups. Results from this investigation suggest that circular fixation may offer some advantages over ORIF such as a shortened length of hospital stay and early return to preinjury activities. Definitive clinical recommendations cannot be made as it also presents higher rates of postoperative complications than ORIF.

Correlation between notch width index assessed via magnetic resonance imaging and risk of anterior cruciate ligament injury: an updated meta-analysis.

PURPOSE: To analyze the correlation between notch width index (NWI) and/or femoral intercondylar notch width (NW) assessed by magnetic resonance imaging (MRI) and risk of anterior cruciate ligament (ACL) injury. METHODS: We searched the PubMed, Embase, China National Knowledge Infrastructure and Wanfang databases for literature reporting a correlation between ACL injury and NWI and/or NW. Subgroup analyses were stratified by ethnicity, sex and control source. The weighted mean difference (WMD) and 95% confidence intervals (95% CIs) were calculated for the ACL injury cases and controls using random- or fixed-effects models. Begg's test and sensitivity analyses were applied to assess publication bias and stability of the results, respectively. RESULTS: Twenty-eight eligible studies were finally enrolled. The NW was significantly narrowerin the ACL injury cases than in the control cases (pooled WMD, - 1.88 [95% CI, - 2.43 to - 1.32]). The results were similar when stratified by ethnicity and sex. Similarly, the NWI was lower in ACL injury cases than in the controls. Asian populations presented similar results when stratified by ethnicity, among the self-control group when stratified by control source, and among men when stratified by sex. No publication bias was identified; however, the sensitivity analysis suggested unstable results in the NWI subgroup analysis. CONCLUSIONS: The current meta-analysis evidenced that the NW assessed via MRI was significantly smaller in ACL injury cases than in the controls. The NWI was lower in ACL injury cases among men. Prevention strategies for ACL injury could be applied for people with intercondylar notch stenosis.

Digital three-dimensional model of lumbar region 4-5 and its adjacent structures based on a virtual Chinese human.

OBJECTIVE: To study the methods for constructing a digitized three-dimensional (3D) model of a virtual lumbar region and its adjacent structures in order to assist anatomical study and virtual surgery. METHODS: Images of DSCF5375-p1 to DSCF5745-p1 were taken from the database of the digitized Virtual Chinese human of Southern Medical University in Guangzhou. This region encompasses the superior facet joint of L4 to the inferior edge of the intervertebral body of L5. The regions of interest were interactively segmented from the images utilizing Adobe Photoshop software. The images were further processed using format conversion and segmentation. Finally, a 3D model of the L4-5 region and its neighboring structures was reconstructed with the assistance of Mimics 10.01 software. RESULTS: A digitized 3D model of this part of the virtual lumbar spine and its adjacent structures was reconstructed. This model allows all constructed structures to be displayed individually or jointly, moved or rotated arbitrarily, setting of different transparencies and convenient measurement of the diameters and angles of the reconstructed structures. The 3D model precisely displays the anatomical relationships between all structures and provides a reliable 3D model for a spinal endoscopic surgery simulation system. CONCLUSION: Visualization of the digitized 3D reconstruction of the virtual lower lumbar region displays this region and its adjacent structures stereoscopically and in actuality, thus providing morphological data concerning anatomy, image diagnosis and virtual operations in this region.