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Background Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied. Methods We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins. Results We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P Conclusions To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins.

Background: HuR/ELAVL1 (embryonic lethal abnormal vision 1) protein exerts important prognostic effects of involving in the pathogenesis and development of acute myeloid leukemia (AML). This study aims to investigate the role of HuR targeted by miR-29b-3p in biological behaviors of AML cells and the involvement of the NF-κB and JAK/STAT signaling pathways. Methods: The expressions of HuR and miR-29b-3p were determined using real-time quantitative PCR and Western blot analysis, and the association between them was analyzed using the Spearman’s coefficient correlation. Next, the potential relationship between HuR and miR-29b-3p was predicted based on data from different biological information databases and verified by the Dual-luciferase reporter gene assay. The effect of miR-29b-3p-meidated HuR expressions on the biological behaviors of AML cells was explored after transfecting lentiviruses, mimics, and inhibitors against miR-29b-3p into AML cells. Then, the expression patterns of Bcl-2 and Bax were detected to understand the apoptosis effect of HuR on AML cells. Phosphorylation levels of NF-κB /p65, IκBα, STAT1, STAT3 and STAT5 were determined to assess the influence of HuR on AML as well as the relationship between the NF-κB and JAK/STAT signaling pathways. Results: HuR was negatively correlated with miR-29b-3p, which was thereby identified as a downstream target of miR-29b-3p in AML. When miR-29b-3p was overexpressed in AML cells, HuR expression was lowered, accompanied by inhibited cell proliferation, migration and invasion, decreased Bcl-2 and Bax levels, as well as inhibited phosphorylation levels of p65, IκBα, STAT1, STAT3 and STAT5. Conclusion: HuR is a direct target of miR-29b-3p. Lowered HuR protein expression by miR-29b-3p inhibits the malignant biological behaviors of AML cells via the inactivation of the NF-κB and JAK/STAT pathways. Key words: HuR, miR-29b-3p, malignant biological behaviors, the NF-κB and JAK/STAT signaling pathways, acute myeloid leukemia

BACKGROUND: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied. METHODS: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins. RESULTS: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P

Dermatomyositis (DM) is a type of autoimmune inflammatory myopathy, which primarily affects the skin and muscle. The underlying mechanisms of DM remain poorly understood. The present study aimed to explore gene expression profile alterations, investigate the underlying mechanisms, and identify novel targets for DM. The GSE48280 dataset, which includes data from five DM and five normal muscle tissue samples, was obtained from the Gene Expression Omnibus. Firstly, differentially expressed genes (DEGs) were screened by limma package in R. Subsequently, functional and pathway enrichment analyses were performed using ClueGO from Cytoscape. Finally, protein‑protein interaction (PPI) networks were constructed using STRING and Cytoscape, in order to identify hub genes. As a result, 180 upregulated and 21 downregulated genes were identified in the DM samples. The Gene Ontology enrichment analysis revealed that the type I interferon (IFN) signaling pathway was the most significantly enriched term within the DEGs. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 27 significant pathways, the majority of which can be divided into the infectious diseases and immune system categories. Following construction of PPI networks, 24 hub genes were selected, all of which were associated with the type I IFN signaling pathway in DM. The findings of the present study indicated that type I IFNs may have a central role in the induction of DM. In addition, other DEGs, including chemokine (C‑C motif) ligand 5, C‑X‑C motif chemokine 10, Toll‑like receptor 3, DEXD/H‑Box helicase 58, interferon induced with helicase C domain 1, interferon‑stimulated gene 15 and MX dynamin‑like GTPase 1, may be potential targets for DM diagnosis and treatment.

BACKGROUND Recent studies have highlighted the potential diagnostic values of microRNAs (miRNA) in various cancers involving oral cancer. This meta-analysis sought to summarize the global diagnostic accuracy of miRNAs for patients with oral cancer (OC). METHODS A systematic review of multiple databases was performed to obtain original studies fulfilling search criteria and the quality of studies was assessed by the QUADAS tool. The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve. Influence analysis, meta-regression, and publication bias assay were all conducted using Stata 12.0 software. The trim-fill adjustment method was used to further assess the possible effect of publication bias. RESULTS A total of 8 studies were included. The SROC analysis showed that miRNA profiling allowed for the discrimination between patients with high-risk oral lesions (OC or pre-cancer) and healthy donors, with a sensitivity of 0.84 (95% CI: 0.78-0.88) and specificity of 0.83 (95% CI: 0.78-0.87), corresponding to an area under curve (AUC) of 0.90. Our subgroup analyses suggested that miRNA signature harbored higher accuracy in diagnosing oral squamous cell carcinoma (OSCC) than pre-cancer lesions (AUC, sensitivity, and specificity of 0.90, 0.83, or 0.82, respectively). Moreover, stratified analyses revealed that parallel miRNA profiling, plasma- and Caucasian-based analyses all conferred promising accuracies for OC detection. The funnel plot assay manifested evidence of a publication bias. After the adjustment by the trim and fill method, the pooled adjusted efforts were slightly attenuated. CONCLUSIONS MiRNA profiles hallmark a potential diagnostic value for detection of OC and potentially malignant disorders. Further studies should be performed to rigorously evaluate the diagnostic accuracy of miRNA profiling for OC.

This study was aimed to investigate the effect of SU11248 on proliferation and apoptosis of leukemia cell line K562 in vitro and its mechanism. The inhibitory effect of 3.2 µg/ml SU11248 on K562 proliferation was tested by MTT assay. The ability of SU11248 to induce apoptosis of K562 cells was examined by TUNEL and DNA ladder. The expression of C-MYC, hTERT and BCR-ABL mRNA in K562 cells was detected by RT-PCR. The protein expression of Akt and p-Akt in K562 cells was detected by Western blot. The results showed that the proliferation of K562 cells was obviously inhibited by 3.2 µg/ml SU11248 in a time-dependent manner. SU11248 could induce K562 cells apoptosis in dose-and time-dependent manner. The mRNA expression of C-MYC, hTERT and BCR-ABL was reduced significantly by SU11248 in a time-dependent manner (P0.05). Western blot detection showed that the expression of p-Akt protein in K562 cells decreased in dose-and time-dependent manner after SU11248 treatment, but the expression of Akt was not significantly changed. It is concluded that SU11248 can inhibit the growth of K562 cells efficiently through inducing apoptosis, its mechanism may be closely relate with the expression down-regulation of C-MYC, hTERT, BCR-ABL and the inhibition of Akt phosphorylation.