[Retracted] Suppressive effect of microRNA­138 on the proliferation and invasion of osteosarcoma cells via targeting SIRT1.

[This retracts the article DOI: 10.3892/etm.2017.4426.].

Analysis of scRNA-seq and bulk RNA-seq demonstrates the effects of EVI2B or CD361 on CD8+ T cells in osteosarcoma.

Osteosarcoma (OS) is a common primary malignant tumor of the bone in children and adolescents. The five-year survival rate is estimated to be ~70% based on the currently available treatment modalities. It is well known that tumor-infiltrating immune cells (TIICs) that are the most important components in the tumor microenvironment can exert a killing effect on tumor cells. Therefore, in the present study, 85 RNA-sequencing OS samples were categorized into high- and low-immune score groups with ESTIAMATE. Based on the immune score groups, 474 differentially expressed genes (DEGs) were acquired using the LIMMA package of R language. Subsequently, 86 DEGs were taken through univariate COX regression analysis, of which 14 were screened out by least absolute shrinkage and selection operator regression analysis. Furthermore, multivariate COX regression analysis was performed to obtain 4 DEGs. Finally, ecotropic virus integration site 2B (EVI2B) or CD361 gene was screened out via Kaplan-Meier analysis. In addition, CIBERSORT algorithm was used to evaluate the proportion of 22 kinds of TIICs in OS. Correlation analysis revealed that the high expression level of EVI2B can elevate the infiltrated proportion of CD8+ T cells. Moreover, analysis of single cell RNA-sequencing transcriptome datasets and immunohistochemical staining uncovered that EVI2B was mainly expressed on CD8+ T cells and that EVI2B could promote the expression of granzyme A and K of CD8+ T cells to exhibit a potent killing effect on tumor cells. Therefore, EVI2B was identified as a protective immune-related gene and contributed to good prognosis in OS patients.

Corrigendum: Single-cell transcriptomics reveals the complexity of the tumor microenvironment of treatment-naive osteosarcoma.

[This corrects the article DOI: 10.3389/fonc.2021.709210.].

A new model of preoperative systemic inflammatory markers predicting overall survival of osteosarcoma: a multicenter retrospective study.

BACKGROUND: The purpose of this study was to investigate the significance of preoperative C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting overall survival (OS) of osteosarcoma, to establish a nomogram of an individualized prognostic prediction model for osteosarcoma. METHODS: Two hundred thirty-five patients with osteosarcoma from multiple centers were included in this study. Receiver operating characteristic (ROC) and Youden index were used to determine the optimal cutoff values ​​for CAR, NLR, and PLR. Univariate analysis using COX proportional hazards model to identify factors associated with OS in osteosarcoma, and multivariate analysis of these factors to identify independent prognostic factors. R software (4.1.3-win) rms package was used to build a nomogram, and the concordance index (C-index) and calibration curve were used to assess model accuracy and discriminability. RESULTS: Univariate analysis revealed that the OS of osteosarcoma is significantly correlated (P < 0.05) with CAR, NLR, PLR, Enneking stage, tumor size, age, neoadjuvant chemotherapy (NACT), and high alkaline phosphatase. Multivariate analysis confirmed that CAR, NLR, Enneking stage, NACT and tumor size are independent prognostic factors for OS of osteosarcoma. The calibration curve shows that the nomogram constructed from these factors has acceptable consistency and calibration capability. CONCLUSION: Preoperative CAR and NLR were independent predictors of osteosarcoma prognosis, and the combination of nomogram model can realize individualized prognosis prediction and guide medical practice.

LncRNA UCA1 accelerates osteosarcoma progression via miR-145 and Wnt/ß-catenin pathway.

Long non-coding (lnc) urothelial cancer associated 1 (UCA1) has been confirmed to participate in osteosarcoma (OS), but its specific mechanism is still under investigation. The study was designed to reveal the interaction between UCA1 and its downstream effector molecules, so as to determine whether there is any interaction of regulating physiological processes in tumor cells. Here, we studied the signaling cascade involving UCA1, miR-145, and HMGA1. The expression of UCA1 and miR-145 levels was interfered to assess their effects on physiological processes of tumor cells. The relationship between UCA1 and miR-145 as well as between HMGA1 and miR-145 was identified by the dual-luciferase reporter (DLR) assay, and the in vivo effect of UCA1 was estimated in nude mouse xenografts. As a result, a negative association was found between UCA1 and miR-145 in OS cells. Both UCA1 knockout and miR-145 over-expression inhibited malignant progression and induced apoptosis in MG-63 and U2OS cells. UCA1 knockout led to an increase in miR-145 and decreases in HMGA1, p-ß-catenin and cyclin D1. In addition, UCA1 upregulation promoted tumor growth in vitro and changed miR-145 and HMGA1 levels in vivo. Moreover, the DLR assay and RNA immunoprecipitation (RIP) showed that UCA1 was likely to regulate HMGA1 levels by sponging miR-145. Overall, the inhibition of UCA1 increases miR-145 levels and decreases HMGA1 levels, thereby exerting an anti-tumor role in OS.

Facile hydrothermal synthesis of manganese sulfide nanoelectrocatalyst for high sensitive detection of Bisphenol A in food and eco-samples.

Bisphenol A (BPA) is a renowned plasticizer, and a key component of various plastics, resins, and food packaging materials. However, BPA have been identified as an endocrine disruption compound and cause severe consequences such as infertility, diabetic, obesity, carcinoma, and possess high risk of exposure in aquatic ecosystem. To this, we crafted an ultrasensitive electrochemical sensor based on the manganese sulfide nanoparticles (MnS NPs) catalyzed electrochemical oxidation of BPA, and its eventual application in rapid screening of BPA contamination. The physiochemical characteristics and electrocatalytic performance of the MnS nanocatalyst have been well studied and utilized in the fabrication of MnS/GCE based BPA sensor. The fabricated BPA sensor has shown a broad dynamic range (20 nM-2.15 mM), lower detection limits (6.52 nM) and promising towards rapid screening of BPA contaminations in food and environmental samples under mimicked real-world conditions with excellent accuracy and precision.

Nanoarchitectonics for Ultrathin Gold Films Deposited on Collagen Fabric by High-Power Impulse Magnetron Sputtering.

Gold nanoparticles conjugated with collagen molecules and fibers have been proven to improve structure strength, water and enzyme degradation resistance, cell attachment, cell proliferation, and skin wound healing. In this study, high-power impulse magnetron sputtering (HiPIMS) was used to deposit ultrathin gold films (UTGF) and discontinuous island structures on type I collagen substrates. A long turn-off time of duty cycle and low chamber temperature of HiPIMS maintained substrate morphology. Increasing the deposition time from 6 s to 30 s elevated the substrate surface coverage by UTGF up to 91.79%, as observed by a field emission scanning electron microscope. X-ray diffractometry analysis revealed signature low and wide peaks for Au (111). The important surface functional groups and signature peaks of collagen substrate remained unchanged according to Fourier transform infrared spectroscopy results. Multi-peak curve fitting of the Amide I spectrum revealed the non-changed protein secondary structure of type I collagen, which mainly consists of α-helix. Atomic force microscopy observation showed that the roughness average value shifted from 1.74 to 4.17 nm by increasing the deposition time from 13 s to 77 s. The uneven surface of collagen substrate made quantification of thin film thickness by AFM difficult. Instead, UTGF thickness was measured using simultaneously deposited glass specimens placed in an HiPIMS chamber with collagen substrates. Film thickness was 3.99 and 10.37 nm at deposition times of 13 and 77 s, respectively. X-ray photoelectron spectroscopy showed preserved substrate elements on the surface. Surface water contact angle measurement revealed the same temporary hydrophobic behavior before water absorption via exposed collagen substrates, regardless of deposition time. In conclusion, HiPIMS is an effective method to deposit UTGF on biomedical materials such as collagen without damaging valuable substrates. The composition of two materials could be further used for biomedical purposes with preserved functions of UTGF and collagen.

The regulatory mechanism of LncRNA-mediated ceRNA network in osteosarcoma.

Aberrantly expressed lncRNAs have been reported to be closely related to the oncogenesis and development of osteosarcoma. However, the role of a dysregulated lncRNA-miRNA-mRNA network in osteosarcoma in the same individual needs to be further investigated. Whole transcriptome sequencing was performed on the tumour tissues and matched paratumour tissues of three patients with confirmed osteosarcoma. Two divergent lncRNA-miRNA-mRNA regulatory networks were constructed in accordance with their biological significance. The GO and KEGG analysis results of the mRNAs in the two networks revealed that the aberrantly expressed lncRNAs were involved in regulating bone growth and development, epithelial cell proliferation, cell cycle arrest and the N-terminal acetylation of proteins. The survival analysis results of the two networks showed that patients with high expression of GALNT3, FAM91A1, STC2 and SLC7A1 end in poorer prognosis. Likewise, patients with low expression of IGF2, BLCAP, ZBTB47, THRB, PKIA and MITF also had poor prognosis. A subnetwork was then constructed to demonstrate the key genes regulated by aberrantly expressed lncRNAs at the posttranscriptional level via the ceRNA network. Aberrantly expressed lncRNAs in osteosarcoma tissues regulate genes involved in cellular proliferation, differentiation, angiogenesis and the cell cycle via the ceRNA network.

ATG16L1 is a Potential Prognostic Biomarker and Immune Signature for Osteosarcoma: A Study Based on Bulk RNA and Single-Cell RNA-Sequencing.

BACKGROUND: Osteosarcoma is a common solid malignancy of the bone in children and adolescents, and its metastasis and recurrence are the principal causes of poor treatment outcomes. METHODS: Autophagy-related genes were used to cluster osteosarcoma patients by consensus clustering analysis using the GSE21257 database. Differentially expressed genes (DEGs) were identified by limma package. Multiple-gene risk signature was constructed using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression analyses. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine gene expression levels. Then, single-cell RNA-sequencing dataset GSE152048 were used to identify the correlation between the DEGs and effector molecules expressed in specific tumor-infiltrating immune cells. RESULTS: Two clusters were identified in the consensus clustering analysis, which were confirmed by principal component analysis. Limma analysis revealed that 15 genes were related, and 9 genes were screened using protein-protein interaction network and LASSO regression analysis. Cox regression analyses identified 5 genes. Combined with survival analysis, only the autophagy related 16 like 1 gene (ATG16L1) was significant. The results of qRT-PCR showed low expression levels of ATG16L1 in tumor cells group. Immune infiltration analysis revealed significantly lower expression of CD8+ T cells in the high ATG16L1 gene expression group. ScRNA-seq revealed that in the ATG16L1+ CD8 + T cell group, the expression of GZMB was lower, whereas the expression of ITGA1 was higher. These results showed that ATG16L1 is an immune-related gene, which is associated with poor prognosis in patients with osteosarcoma. CONCLUSION: ATG16L1 is a potential prognostic biomarker and immune signature and may be a therapeutic target for osteosarcoma.

Significance of the neutrophil-to-lymphocyte ratio in predicting the response to neoadjuvant chemotherapy in extremity osteosarcoma: a multicentre retrospective study.

BACKGROUND: At present, no predictive factor has been validated for the early efficacy of neoadjuvant chemotherapy (NACT) in osteosarcoma. The purpose of this study was to investigate the significance of the neutrophil-to-lymphocyte ratio (NLR) in predicting the response to NACT in extremity osteosarcoma. METHODS: Pathological complete response (pCR) was used to assess the efficacy of NACT. Receiver operating characteristic (ROC) curves and the Youden index (sensitivity + specificity-1) were used to determine the optimal cut-off values of the NLR. Univariate and multivariate analyses using logistic regression models were conducted to confirm the independent factors affecting the efficacy of NACT. RESULTS: The optimal NLR cut-off value was 2.36 (sensitivity, 80.0%; specificity, 71.3%). Univariate analysis revealed that patients with a smaller tumour volume, lower stage, lower NLR and lower PLR were more likely to achieve pCR. Multivariate analyses confirmed that the NLR before treatment was an independent risk factor for pCR. Compared to patients with a high NLR, those with a low NLR showed a more than 2-fold higher likelihood of achieving pCR (OR 2.82, 95% CI 1.36-5.17, p = 0.02). CONCLUSION: The NLR is a novel and effective predictive factor for the response to NACT in extremity osteosarcoma patients. Patients with a higher NLR showed a lower percentage of pCR after NACT.

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone.

Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma.

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

Construction of autophagy prognostic signature and analysis of prospective molecular mechanisms in skin cutaneous melanoma patients.

BACKGROUND: Autophagy is closely related to skin cutaneous melanoma (SKCM), but the mechanism involved is unclear. Therefore, exploration of the role of autophagy-related genes (ARGs) in SKCM is necessary. MATERIALS AND METHODS: Differential expression autophagy-related genes (DEARGs) were first analysed. Univariate and multivariate Cox regression analyses were used to evaluate the expression of DEARGs and prognosis of SKCM. Further, the expression levels of prognosis-related DEARGs were verified by immunohistochemical (IHC) staining. Finally, gene set enrichment analysis (GSEA) was used to explore the underlying molecular mechanisms of SKCM. RESULTS: Five ARGs (APOL1, BIRC5, EGFR, TP63, and SPNS1) were positively correlated with the prognosis of SKCM. IHC verified the results of the differential expression of these 5 ARGs in the bioinformatics analysis. According to the receiver operating characteristic curve, the signature had a good performance at predicting overall survival in SKCM. The signature could classify SKCM patients into high-risk or low-risk groups according to distinct overall survival. The nomogram confirmed that the risk score has a particularly large impact on the prognosis of SKCM. Calibration plot displayed excellent agreement between nomogram predictions and actual observations. Principal component analysis indicated that patients in the high-risk group could be distinguished from those in low-risk group. Results of GSEA indicated that the low-risk group is enriched with aggressiveness-related pathways such as phosphatidylinositol-3-kinase/protein kinase B and mitogen-activated protein kinase signalling pathways. CONCLUSION: Our study identified a 5-gene signature. It revealed the mechanisms of autophagy that lead to the progression of SKCM and established a prognostic nomogram that can predict overall survival of patients with SKCM. The findings of this study provide novel insights into the relationship between ARGs and prognosis of SKCM.

Osseointegrating and phase-oriented micro-arc-oxidized titanium dioxide bone implants.

Here, we present a bone implant system of phase-oriented titanium dioxide (TiO2) fabricated by the micro-arc oxidation method (MAO) on ß-Ti to facilitate improved osseointegration. This (101) rutile-phase-dominant MAO TiO2 (R-TiO2) is biocompatible due to its high surface roughness, bone-mimetic structure, and preferential crystalline orientation. Furthermore, (101) R-TiO2 possesses active and abundant hydroxyl groups that play a significant role in enhancing hydroxyapatite formation and cell adhesion and promote cell activity leading to osseointegration. The implants had been elicited their favorable cellular behavior in vitro in the previous publications; in addition, they exhibit excellent shear strength and promote bone-implant contact, osteogenesis, and tissue formation in vivo. Hence, it can be concluded that this MAO R-TiO2 bone implant system provides a favorable active surface for efficient osseointegration and is suitable for clinical applications.

Long Noncoding RNA CCDC144NL-AS1 Promotes the Oncogenicity of Osteosarcoma by Acting as a Molecular Sponge for microRNA-490-3p and Thereby Increasing HMGA2 Expression.

PURPOSE: The long noncoding RNA CCDC144NL antisense RNA 1 (CCDC144NL-AS1) exhibits important functions in gastric cancer. In this study, we aimed to investigate the roles of CCDC144NL-AS1 in modulating the phenotype of osteosarcoma (OS) cells in vitro and in vivo and elucidate its underlying mechanisms. METHODS: Reverse transcription quantitative polymerase chain reaction (PCR) was performed to determine the expression level of CCDC144NL-AS1 in OS tissues and cell lines. The proliferation, apoptosis, migration, and invasion in vitro as well as tumor growth in vivo were determined in OS cells using the Cell Counting Kit 8 assay, flow cytometric analysis, transwell migration and invasion assays, and xenograft experiments, respectively. Bioinformatics analysis was performed to identify the potential microRNA targets of CCDC144NL-AS1, which were subsequently confirmed using the luciferase reporter assay, RNA immunoprecipitation assay, reverse transcription quantitative PCR, Western blotting, and rescue experiments. RESULTS: CCDC144NL-AS1 expression was upregulated in OS tissues and cell lines. Patients with OS who exhibited high CCDC144NL-AS1 expression had shorter overall survival than those who exhibited low CCDC144NL-AS1 expression. Functionally, interference in CCDC144NL-AS1 expression led to a notable decrease in the proliferation, migration, and invasion of OS cells and an increase in cell apoptosis in vitro. Furthermore, CCDC144NL-AS1 knockdown impaired OS tumor growth in vivo. Mechanistically, CCDC144NL-AS1 directly bound to miR-490-3p in OS cells, where it functioned as a molecular sponge and subsequently increased the expression of high-mobility group AT-hook 2 (HMGA2). Rescue experiments further demonstrated that miR-490-3p suppression or HMGA2 restoration abated CCDC144NL-AS1 deficiency-induced cancer-inhibitory actions in OS cells. CONCLUSION: CCDC144NL-AS1 exhibits pro-oncogenic roles in OS by functioning as a sponge for miR-490-3p and increasing HMGA2 expression. Our findings suggest that greater understanding of the CCDC144NL-AS1/miR-490-3p/HMGA2 pathway can provide useful information for OS diagnosis, prognosis, and therapy.

lncRNA LSINCT5 Regulates miR-20a-5p/XIAP to Inhibit the Growth and Metastasis of Osteosarcoma Cells.

BACKGROUND: More and more evidence has shown that non-coding RNA (ncRNA), including long ncRNA (lncRNA) and micro RNA (miRNA), plays a crucial regulatory role in osteosarcoma (OS). Previously, we revealed a Rho-related coiled coil incorporating protein kinase 1(XIAP). A transfer-related gene is negatively regulated by microRNA-20a-5p (miR-20a-5p) and plays the role of oncogene in OS. It is not clear if any lncRNA is involved in the axial upstream of miR-20a-5p/XIAP. METHODS: Expression of LSINCT5 and miR-20a-5p/XIAP in OS tissues was determined through qRT-PCR (qP). The proliferation and migration/invasion activity of OS cells were tested through CCK-8/and transwell assay, respectively. The changes on expression of XIAP were examined through qRT-PCR and Western blot (WB). Targeted binding between LSINCT5, miR-20a-5p, and XIAP has been verified using dual luciferase reporter gene analysis, RNA Immunoprecipitation (RIP), and RNA pull-down experiments. The effect of LSINCT5 on tumor growth was determined by tumor allograft test. RESULTS: In this study, elevated LSINCT5 was found in OS tissue samples and OS cell strains, and the increased LSINCT5 was strongly related to the adverse prognosis of clinical patients. Functional assays showed that inhibition of LSINCT5 could up-regulate miR-20a-5p-mediated OS cells proliferation and metastasis. WB analysis and qP analysis showed that LSINCT5 regulated XIAP by mediating miR-20a-5p. Further cell behavior experiments showed that LSINCT5 acted as a miR-20a-5p sponge to inhibit proliferation and metastasis caused by XIAP. Finally, the results of animal models in vivo showed that LSINCT5 could regulate the tumor growth of OS. CONCLUSION: LncRNA LSINCT5 acts as an oncogene and promotes XIAP mediated growth and metastasis as competitive endogenous RNA (ceRNA) in OS.

PLK1 contributes to autophagy by regulating MYC stabilization in osteosarcoma cells.

BACKGROUND: PLK1, a typical PLK protein, is the main driver of cancer cell growth and proliferation. It is an inhibitor of the protein kinases that is currently being investigated in clinical studies. It is often used as a tumor marker, as high PLK1 expression correlates with poor prognosis in cancer. Overexpression of MYC is a hallmark of many human cancers. MYC modulates the transcription of thousands of genes that required to coordinate a series of cellular processes, including those essential for growth, proliferation, differentiation, self-renewal and apoptosis. To date, functions of PLK1 and MYC on tumor are mostly studied in separate researches, and studies on their mutual crosstalk are lacking. PURPOSE: To investigate the mechanism of PLK1 and MYC in regulating progress of osteosarcoma. METHODS: Protein level was examined using Western blot. Animal experiments were performed with female FOX CHASE severe combined immunodeficient mice. Mice were randomly divided into experimental or control groups. RESULTS: PLK1 or MYC promoted the proliferation of osteosarcoma cells through the autophagy pathway. PLK1 contributed to MYC protein stabilization. PLK1 inhibition enhanced MYC degradation in osteosarcoma cells. PLK1 inhibition led to a marked decline in MYC protein abundance. The representative MYC target genes were deregulated by PLK1 inhibitors. BI2536 treatment caused a significant delay in xenograft tumor growth in mice injected with U-2 OS cells subcutaneously, with lower mean tumor weight compared to the control group. CONCLUSION: PLK1 is crucial for MYC stabilization. It promotes cell proliferation by autophagy pathway in osteosarcoma cells. Data validate PLK1 as a potential therapeutic target in osteosarcoma caused by MYC-amplified.

Expression and predictive value of miR-489 and miR-21 in melanoma metastasis.

BACKGROUND: Melanoma is a highly malignant skin tumour, and is one of the most rapidly growing malignant tumors in recent years. According to statistics, the morbidity of cancer increases with age, accounting for 1.6% of new cancer cases and 0.6% of deaths worldwide. Melanoma has a serious impact on society and families, thus it is of great significance to find biological markers related to the diagnosis and treatment of melanoma. AIM: To explore the expression and predictive value of mir-489 and mir-21 in melanoma metastasis. METHODS: A total of 60 patients with malignant melanoma treated at our hospital from June 2017 to December 2018 were selected as a research group, while 40 healthy subjects were selected as a control group. qRT-PCR technique was used to detect miR-489 and miR-21 in serum of the two groups. ROC curve was drawn to evaluate the predictive value and diagnostic efficiency. Spearman test was used for correlation analysis. Logistic single- and multiple-factor analyses were performed to identify the risk factors related to melanoma metastasis. RESULTS: The expression of miR-489 in the research group was significantly lower than that in the control group (P < 0.001). However, the expression of miR-21 in the research group was significantly higher than that in the control group (P < 0.001). The expression of miR-489 and miR-21 was related to TNM stage and metastasis (P < 0.001). In the diagnosis of melanoma patients, the sensitivity, specificity, and AUC of miR-489 alone were 75.56%, 80.00%, and 0.852, respectively. The sensitivity, specificity, and AUC of miR-21 alone were 77.78%, 82.22%, and 0.844, respectively. MiR-489 was negatively correlated with TNM stage of melanoma (r = -0.612, P < 0.001), while miR-21 was positively correlated with TNM stage (r = 0.609, P < 0.001). Logistic single- and multiple-factor regression analyses showed that TNM stage, miR-489, and mir-21 were independent risk factors for malignant melanoma metastasis. CONCLUSION: MiR-489 and miR-21 may participate in the process of melanoma occurrence, development, and metastasis, and can be used as potential serum biomarkers for melanoma metastasis diagnosis and disease assessment.

Safety and efficacy of microwave ablation for breast cancer thoracic metastases.

BACKGROUND: The objective of the study was to assess the safety and efficacy of microwave ablation (MWA) for breast cancer thoracic metastasis. MATERIALS AND METHODS: Twelve patients in our institution with a single lesion of breast cancer thoracic metastases received MWA and invasive spine surgery from August 2014 to November 2016. MWA was executed using the MWA system (2,450 MHz) at 40 W or 50 W with thermometers to control the ablation end points. The pathology of thoracic metastases was confirmed through intraoperative biopsy before ablation. The postoperative complications were recorded. The patients were followed up at 1, 3 and 6 months with contrast-enhanced computed tomography and magnetic resonance imaging to monitor for tumor recurrence. RESULTS: The average duration of follow-up for breast cancer thoracic metastases patients (mean age 52.7±8.4 years) was 10.2 months. The rate of postoperative main complications was 8.3% (1/12). The recurrence rate was 16.6% (2/12) as confirmed by persistent enhancement. CONCLUSION: MWA may be used as the adjuvant treatment for thoracic metastases of breast cancer. Results showed that few significant complications and less local recurrence occurred during the follow-up stage. Future research should aim at discovering more about the time controls for microwave-tissue interaction and treatment parameters before widespread use.

Tunability of p- and n-channel TiOx thin film transistors.

To acquire device-quality TiOx films usually needs high-temperature growth or additional post-thermal treatment. However, both processes make it very difficult to form the p-type TiOx even under oxygen-poor growth condition. With the aid of high energy generated by high power impulse magnetron sputtering (HIPIMS), a highly stable p-type TiOx film with good quality can be achieved. In this research, by varying the oxygen flow rate, p-type γ-TiO and n-type TiO2 films were both prepared by HIPIMS. Furthermore, p- and n-type thin film transistors employing γ-TiO and TiO2 as channel layers possess the field-effect carrier mobilities of 0.2 and 0.7 cm2/Vs, while their on/off current ratios are 1.7 × 104 and 2.5 × 105, respectively. The first presented p-type γ-TiO TFT is a major breakthrough for fabricating the TiOx-based p-n combinational devices. Additionally, our work also confirms HIPIMS offers the possibility of growing both p- and n-type conductive oxides, significantly expanding the practical usage of this technique.