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POU3F4, a transcription factor (TF), has been proved to be critical regulator of inner ear and pancreas development and neurogenesis. Despite growing evidence confirming the indispensable role of POU3F4 in carcinogenesis of specific cancers, the pan-cancer assessment of POU3F4 remains scanty. As a result, we aimed at studying the prognostic value of POU3F4 in thirty-three cancers and to study the underlying function in immunity. On the grounds of data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression and Gene Set Cancer Analysis, we made use of numerous bioinformatics ways to study the prospective carcinogenic effects of POU3F4, DNA methylation, RNA methylation, tumor mutation burden (TMB), mismatch repair (MMR) gene, microsatellite instability (MSI), POU3F4-prognosis interrelation, and immune cell infiltration (ICI) in discrepant tumors. The analysis yielded that the POU3F4 expression was at a low rate in most cancers, while it was higher in breast invasive carcinoma, glioblastoma multiforme, liver hepatocellular carcinoma, and thyroid carcinoma. Additionally, POU3F4 had a link with the prognosis of discrepant cancers, either positively or negatively. Expression of POU3F4 showed relevance to MSI (4 cancer types) and TMB (6 cancer types), and exhibited striking relevance to DNA methylation (13 cancer types) and RNA methylation (most cancers). Additionally, its expression was associated with tumor immune microenvironment, immune-related genes, ICI and drug resistance in different cancers. In vitro experiments had shown that POU3F4 could increase cell viability, proliferation and migration of glioma cells. Our research reveals that concerning the indispensable function in carcinogenesis and tumor immunity, POU3F4 is deemed as a prognostic hallmark in discrepant malignancies.

Calcific aortic valve disease (CAVD) is the most common heart relating disease with high morbidity and mortality, especially in elderly population. A previous recent multi-omics study suggested a novel CAVD molecular interaction network contained miR-21-5p. To confirm the association between miR-21-5p and CAVD progression, in this study, we investigated the roles of miR-21-5p in the mineralization process of aortic valves obtained from CAVD patients and paired normal tissues. Valvular intersitial cells (VICs) were isolated from clinic samples and maintained for the following assays. RT-qPCR was utilized for detection of miR-21-5p and related protein expression levels to confirm the related factors in CAVD progression. Western blotting was applied to strengthen the results of RT-qPCR and confirm osterogenic differentiation of VICs via biomarker detection. The staining of alkaline phosphatase (ALP) and alizarin red was performed to assess the degree of VIC mineralization. We found that miR-21-5p was remarkably increased in calcified aortic valves (AVs) whereas TGFBI was diminished in CAVD samples compared to the paired normal tissues from CAVD patients. Additionally, TGFBI was targeted by miR-21-5p. Furthermore, overexpressing TGFBI could block VIC osteogenic differetiation mediated by miR-21-5p. To sum up, miR-21-5p promotes VIC osteogenic differentiation and calcificaion via TGFBI in CAVD progression. Our work might bring a sight on underlying mechansims of CAVD progression and provide a possible therapeutic target for diagnosis and treatment.

Background Esophageal cancer (EC) is one of the aggressive gastrointestinal malignancies. It has been reported that microRNAs (miRNAs) play key roles during the tumorigenesis of EC. To identify novel potential targets for EC, differential expressed miRNAs (DEG) between EC and adjacent normal tissues were analyzed with bioinformatics tool. Methods The differential expression of miRNAs between EC and adjacent normal tissues was analyzed. CCK-8 and Ki67 staining were used to detect the cell proliferation. Flow cytometry was performed to test the cell apoptosis. The correlation between miR-7-5p and KLF4 was detected by dual-luciferase report assay. Gene and protein expression in EC cells or in tissues were measured by qRT-PCR and Western blot, respectively. Cell migration and invasion were detected with transwell assay. Xenograft mice model was established to investigate the role of miR-7-5p in EC tumorigenesis in vivo. Results MiR-7-5p was found to be negatively correlated with the survival rate of patient with EC. In addition, downregulation of miR-7-5p significantly inhibited the growth and invasion of EC cells. Meanwhile, miR-7-5p directly targeted KLF4 in EC cells. Moreover, downregulation of miR-7-5p inhibited the tumorigenesis of EC via inactivating MAPK signaling pathway in vivo. Conclusion Downregulation of miR-7-5p notably suppressed the progression of EC via targeting KLF4. Thus, miR-7-5p might serve as a new target for the treatment of EC.

Background Non-small cell lung cancer (NSCLC) is a part of the most common cancers in the world. A lot of efforts have been made to clarify the etiology of non-small cell lung cancer, but the molecular mechanism of non-small cell lung cancer is still unclear. Methods In order to identify candidate genes in the occurrence and progression of non-small cell lung cancer, GSE19804 GSE118370 GSE19188 GSE27262 and GSE33532 microarray data sets were downloaded from the Gene Expression General (GEO) database. Identify differentially expressed genes (DEGS) and perform functional enrichment analysis. The protein-protein interaction network (PPI) was constructed, and the module analysis was performed using STRING and Cytoscape. A total of 562 DEGS were identified, consisting of 98 downregulated genes and 464 upregulated genes. Abundant functions and pathways of DEGS include p53 signaling pathway, Cell adhesion molecules,Leukocyte transendothelial migration,Vascular smooth muscle contraction,Complement and coagulation cascades and Axon guidance. Tumor immunity was assessed to investigate the functions of hub genes. Results Totally 562 genes were found to be dysregulated. 12 genes were considered to be the hub genes. NUF2 was considered as the potential immunotherapeutic targets with future clinical significance.12 hub genes were detected, and biological process analysis showed that these genes are mainly enriched in p53 signaling pathway,Progesterone-mediated oocyte maturation,Cell cycle, Oocyte meiosis and Cellular senescence Survival analysis shows that NUF2 may be linked to the occurrence, invasion or recurrence of non-small cell lung cancer. Conclusion NUF2 genes discovered in this study help us include the molecular mechanisms of the occurrence and progression of non-small cell lung cancer, and provide candidate targets for the diagnosis and treatment of non-small cell lung cancer.

Previous studies have shown that long intergenic non-protein coding RNA 00518 (LINC00518) are essential for the cell growth and metastasis of human cancer. However, the role of LINC00518 in lung adenocarcinoma (LUAD) is still unknown. This research put emphasis on the function of LINC00518 on the cell growth of LUAD. The lncRNA, miRNA and mRNA expression were measured by using qRT-PCR. Protein levels were measured by using Western blotting. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Bioinformatic analysis and luciferase reporter assays were chosen to confirm the mechanism of LINC00518 in LUAD. We found that LINC00518 was highly expressed in LUAD specimens and the high-expression was negatively correlated with the overall survival rates. This finding was also proved in the LUAD cell lines. Through a series of in vitro and in vivo experiments, we proved that LICN00518 promoted the cell growth of LUAD by regulating the cell cycle. Moreover, LICN00518 upregulated the expression of MECP2 by mutagenesis of miR-185-3p. The results suggested that LICN00518 could be used as a survival indicator and potential therapeutic target for LUAD patients.

Background: Many esophageal cancer patients with lymph node metastases during surgery are recommended for postoperative radiation therapy. However, postoperative radiation could cause many serious adverse reactions. Here, we introduce a new radical operation for esophageal cancer under bilateral thoracoscopy to reduce the adverse reactions of postoperative radiation.Case presentation: A 50-year-old man was diagnosed with Esophageal squamous cell carcinoma by gastroscopy. Because the tumor was found to have obvious invasion and rapid pathology showed positive lymph nodes during the operation, which is in line with the postoperative chemotherapy indication, we adopted a bilateral thoracic approach for esophageal cancer to reduce adverse reactions of postoperative radiotherapy. We successfully guided the tubular stomach through the left thoracic aortic arch to the left thoracic cavity, and then performed an esophageal-tubular stomach anastomosis on the left neck under bilateral thoracoscopy to reduce radiation exposure to the remnant stomach. The operation went well.Conclusion: For patients with esophageal cancer who are found to have radiotherapy indications during the operation, bilateral thoracoscopic radical resection of esophageal cancer should be preferred during the operation to improve the postoperative radiotherapy effect.

This study aimed to investigate the function of long non-coding RNA FOXD2 adjacent opposite strand RNA 1 (lncRNA FOXD2-AS1) during the progression of esophagus cancer (EC) and explore its underlying molecular mechanisms. The level of FOXD2-AS1 in EC tissues and paracancerous tissues was detected by using RT-qPCR; ROC curve was used to evaluate the diagnostic value of FOXD2-AS1 for EC. In addition, CCK8 assay and immunofluorescence staining assay were used to detect the proliferation of Eca-109 and TE-1 cells. To investigate the function of FOXD2-AS1 on cell apoptosis and cell cycle, flow cytometry was performed. To detect the invasion ability of EC cells, transwell invasion assay was performed. Starbase3.0 and Targetscan were used to predict the target genes of FOXD2-AS1 and miR-145-5p, and protein expressions were detected with western blot. We found FOXD2-AS1 was significantly upregulated in EC tissues compared with adjacent normal tissues, which was positively correlated with clinicopathological parameters of patients with EC. Downregulation of FOXD2-AS1 inhibited the proliferation and invasion by inducing apoptosis of EC cells. Moreover, FOXD2-AS1 may regulate the expression of CDK6 by targeting miR-145-3p. Meanwhile, silencing of FOXD2-AS1 caused G1 phase arrest of EC cells by reducing the expression of CDK6. In conclusion, silening FOXD2-AS1 significantly inhibited the proliferation and invasion of EC cells by regulating the miR-145-5p/CDK6 axis. Therefore, FOXD2-AS1 might be used as diagnostic biomarker and therapeutic target for EC.

Bladder cancer-associated transcript 1 (BLACAT1) is a novel identified long noncoding RNA (lncRNA) in bladder cancer, and has been suggested to function as an oncogenic lncRNA in several types of human cancer. However, its involvement in the progression of small-cell lung cancer (SCLC) remained unknown. The aim of our study was to investigate the clinical value and biological function in SCLC. In our results, BLACAT1 expression was increased in SCLC tissues and cell lines compared with paired adjacent normal tissues and bronchial epithelial cell lines, respectively. In addition, BLACAT1 high-expression was obviously associated with advanced clinical stage, large tumor size, more lymph node metastasis, present distant metastasis, and poor prognosis. Furthermore, multivariate analysis indicated that high-expression of BLACAT1 acted as an independent poor prognostic factor for overall survival in SCLC cases. The loss-of-function studies suggested that of BLACAT1 suppressed SCLC cell proliferation, migration, and invasion, and induced G0/G1 phase arrest. In conclusion, BLACAT1 is associated with the malignant status and prognosis in patients with SCLC, and functions as an oncogenic lncRNA in regulating cell proliferation and motility, suggesting BLACAT1 may act as a potential target for SCLC prevention and treatment.

Background Aristolochic acid nephropathy (AAN) is a type of drug-induced nephropathy that may result in acute kidney injury and is associated with a potentially progressive course of kidney fibrosis and upper tract urothelial carcinoma. Aristolochic acids (AAs) are a group of toxins commonly present in plants of the genera Aristolochia and Asarum, which are found worldwide. AAN still occurs in Asian and Balkan regions. The progressive lesions and mutational events initiated by AAs are irreversible, and no effective therapeutic regimen for AAN has been established. Furthermore, more people are at risk of this disease due to casual exposure to AAs. This study performed a scientometric analysis of global research literature focusing on AAN. Methods The Web of Science database was searched to identify all publications pertaining to "aristolochic acid nephropathy" or "Balkan endemic nephropathy" using these terms as key words to search the literature from 1971 to 2019. The collected data included the document type, author, journal, publication year, citation reports, and country of publication, and were analyzed using the VOSviewer software. Results A total of 1251 records were initially obtained. Publication types, including "meeting abstract," "letter," "editorial material," and "proceedings paper" were excluded, which left 1083 publications comprising 923 articles and 160 reviews. English was the predominant language of the publications. China had the most number of articles published with 217 (20.0%), followed by the USA with 186 articles (17.2%), and Germany with 138 articles (12.7%). Kidney International, Food and Chemical Toxicology, and Toxins were the 3 most active journals in publishing articles related to AAN. The total number of citations received by all publications was 39,970, with an average of 36.91 citations per article (range: 0-1769). The literature mainly focused on apoptosis, oxidative stress, and inflammation in AAN. Conclusion This study indicated that AAN is a significant topic in nephrology research, as shown by the large number of publications. The literature has mainly focused on the mechanisms of AA-induced nephropathy.

Non‑small‑cell lung cancer (NSCLC) accounts for ~80% of human lung cancers that result in mortalities worldwide. Metastasis‑associated in colon cancer‑1 (MACC‑1) has been demonstrated to be significantly expressed in cases of NSCLC and promotes tumor cell migration and metastasis through transactivation of the metastasis‑inducing hepatocyte growth factor/MET proto‑gene, receptor tyrosine kinase (HGF/MET) signaling pathway. The present study constructed a chimeric antibody (Chanti‑MACC‑1) targeting MACC‑1 and investigated its potential as a molecular therapeutic target in the treatment of NSCLC therapy. The expression of MACC‑1 was detected by reverse transcription‑quantitative polymerase chain reaction and western blotting in lung cancer cell lines and tissues. MTT assay was used to detect proliferation of A549 cells treated by Chanti‑MACC‑1, whereas the functional and regulatory effects of Chanti‑MACC‑1 in the migration and metastasis of NSCLC cells was investigated by a cell invasion assay. The therapeutic effect and survival time was observed in animal models. The results demonstrated that MACC‑1 expression was increased and overexpression of MACC‑1 promoted the progression of the cell cycle, significantly promoted NSCLC cell growth and enhanced tumor migration and invasion through the HGF/MET signaling pathway. It was further demonstrated that Chanti‑MACC‑1 efficiently suppressed MACC‑1 expression and significantly inhibited NSCLC cell proliferation, migration and invasion by blocking the HGF/MET signaling pathway. The data revealed that Chanti‑MACC‑1 was not only beneficial for tumor remission, however additionally contributed to the long‑term survival of NSCLC ‑bearing mice. The findings of the present study indicated that MACC‑1 was significantly upregulated and promoted tumor cell growth and migration in NSCLC cells and tissues via transactivation of the metastasis‑inducing HGF/MET signaling pathway. However, Chanti‑MACC‑1significantly inhibited tumor growth and metastasis, which suggested that MACC‑1 may be essential for tumor initiation and progression by negatively regulating tumor suppressors.

Huiwen Chang, Jianxiang Song, Jixiang Wu, Yajun Zhang Department of Cardiothoracic Surgery, Yancheng Third People’s Hospital, The Affiliated Yancheng Hospital of Southeast University, Yancheng, Jiangsu 224001, PR China Purpose: E2F transcription factor 8 (E2F8) is a novel member of the E2F family, but its function in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to research the function of E2F8 in ESCC. Materials and methods: We used quantitative real-time PCR and Western blot analyses to detect the expression pattern of E2F8 in ESCC. The effects of E2F8 on proliferation were investigated by Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation assays. We also confirmed the function of E2F8 invivo. Results: E2F8 expression was upregulated in ESCC, and promoted cell proliferation and influenced the expression of CCND1/p21. Downregulation of E2F8 expression inhibited cell proliferation invivo. Conclusion: E2F8 was identified as a new potential oncogene in ESCC. Keywords: E2F8, cell cycle, ESCC, cell proliferation

Background: Non-small cell lung carcinoma (NSCLC) is a common malignant tumor with poor prognosis. CircRNA-100876 has been considered to be involved in NSCLC. However, the mechanism by which circRNA_100876 mediated the progression of NSCLC remains unclear. Methods: CCK8 assay and immunofluorescence were used to detect cell proliferation. Flow cytometry and transwell assay were performed to analyze cell apoptosis, migration and invasion, respectively. Verification of possible target for circRNA_100876 and related miR-636 were done using luciferase assay. In addition, western blot was performed to detect the protein expressions in NSCLC cells. Results: Silencing of circRNA_100876 notably inhibited the proliferation of NSCLC cells. Moreover, downregulation of circRNA_100876 significantly induce the apoptosis of NSCLC cells via mediation of apoptosis-related proteins. In addition, silencing of circRNA_100876 significantly inhibited migration and invasion of NSCLC cells. MiR-636 was the downstream target of circRNA_100876. Meanwhile, RET was the direct target of miR-636. Finally, circRNA_100876 shRNA2 notably suppressed the progression of NSCLC through PI3K/Akt signaling. Conclusion: CircRNA_100876 knockdown notably suppressed the progression of NSCLC through regulation of miR-636/RET axis, which may serve as a potential target for treatment of NSCLC.

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA) are the two most common types of esophageal cancer, which is the sixth highest cause of cancer‑associated mortality and the eighth most common cancer worldwide. Gene associated with retinoid‑interferon (IFN)‑induced mortality‑19 (Grim‑19) is reported to be a cell death activator that may be used to define mechanisms involved in IFN‑β‑ and retinoic acid‑induced cell death and apoptosis in a number of tumor cell lines. The present study constructed a recombinant adenovirus expressing Grim‑19 (rAd‑Grim‑19) and investigated its therapeutic outcomes in ESCC cells and tumor‑bearing mice. Grim‑19 expression was detected in EC‑109 (ESCC) cells by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Tumor cell death and apoptosis induced by rAd‑Grim‑19 in EC‑109 cells were analyzed by flow cytometry. The inhibitory effects of rAd‑Grim‑19 on EC‑109 growth were determined by MTT assays. Furthermore, the therapeutic effects of rAd‑Grim‑19 were investigated in EC‑109‑bearing mice. The results demonstrated that Grim‑19 mRNA and protein expression was downregulated in EC‑109 esophageal carcinoma cells compared with Het‑1A normal esophageal epithelial cells. In addition, EC‑109 cells exhibited a significant reduction in tumor cell growth in the rAd‑Grim‑19 group compared with the control groups. Furthermore, rAd‑Grim‑19 increased EC‑109 cell apoptosis compared with the control group. These results indicated that rAd-Grim-19 may regulate tumor cell growth and apoptosis. Additionally, the results demonstrated that rAd‑Grim‑19 led to beneficial outcomes and prolonged the survival of esophageal tumor‑bearing mice. In conclusion, the present study demonstrated that rAd‑Grim‑19 may have potential as an antitumor agent for esophageal neoplasms and may therefore be beneficial for patients with esophageal neoplasms.

Jianxiang Song,1,2,* Woda Shi,1,2,* Yajun Zhang,2 Mingzhong Sun,3 Xiaodong Liang,3,4 Shiying Zheng1 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 2Department of Cardiothoracic Surgery, 3Department of Clinical Laboratory, 4Department of Pathology, The Third People’s Hospital of Yancheng City, Yancheng, Jiangsu Province, People’s Republic of China *These authors contributed equally tothis work Abstract: Biomarkers that can serve as diagnostic and prognostic indicators of esophageal squamous cell carcinoma (ESCC) are urgently needed to help improve patient outcomes. Here, the expression of epidermal growth factor receptor (EGFR) and costimulatory molecule B7-H3, both of which have been implicated in tumor onset and progression in certain tumors, was investigated in relation to the clinical characteristics and survival outcomes of patients with ESCC. ESCC tissue samples were analyzed for 100 patients. Tumor and patient characteristics were recorded. Tissues were investigated for EGFR and B7-H3 staining by immunohistochemistry. Patients were followed for up to 96 months to determine overall survival (OS) and progression-free survival (PFS). High expression for EGFR (68.0%) and B7-H3 (66.0%) was observed in the majority of cases. High expression of either EGFR or B7-H3 was correlated with tumor invasion depth and clinical stage (P

We attempt to dissect the pathology of non-small cell lung cancer (NSCLC) patients at different stages and discover the novel candidate genes. Microarray data (GSE21933) were retrieved from the Gene Expression Omnibus database. The differential expression profiles of lung tumor tissues during different stages were analyzed. The significantly altered functions and pathways were assessed and the key nodes in a protein-protein interaction (PPI) network were screened out. Then, the coexpression gene pairs and tumor-related genes were assessed. RT-PCR analysis was performed to validate the candidate gene, natural killer-tumor recognition sequence (NKTR). The number of differentially expressed genes (DEGs) for stage IB, IIB, IIIA and IV tumors were 499, 602, 592 and 457, respectively. Most of the DEGs were NSCLC-related genes identified through literature research. A few genes were commonly downregulated in all the 4 stages of tumors, such as CNTN6 and LBX2. The DEGs in early‑stage tumors were closely related with the negative regulation of signal transduction, the apoptosis pathway and the p53 signaling pathway. DEGs in late-stage tumors were significantly enriched in transcription, response to organic substances and synapse regulation-related biological processes. A total of 16 genes (including NKTR) made up the significant coexpression network. NKTR was a key node in the PPI network and was significantly upregulated in lung cancer cells. The mechanism of NSCLC progression in different tumor stages may be different. NKTR may be the target candidate for NSCLC prevention and treatment.

We read with great interest the study by Martinez-Lopez-de-Castro et al (in July 2018),1 which analysed the factors leading to a greater satisfaction among patients visiting the outpatient hospital pharmacy. We strongly agree with their findings that the information provided, resolution of doubts, pharmacist’s personal treatment of the patient and time devoted to the patient are important in meeting patient preferences and expectations. We are from a district general hospital in China with 1800 beds. With electronic prescriptions and an automatic drug delivery machine, which were introduced in 2014, considerable time and manpower is saved. However, a neutral third-party investigation report shows that the patient satisfaction of the outpatient hospital pharmacy did not exhibit a consistent upward trend. We sought to explore a method to improve the quality of pharmaceutical care by setting up full-time clinical pharmacists to resolve any doubts the patients raised during the treatment, showing the patients how …

Background Methimazole is an antithyroid drug that is widely used for the treatment of hyperthyroidism. As an inhibitor of the enzyme thyroperoxidase, methimazole is generally well-tolerated. However, there have been increasing reports of methimazole-induced liver damage, although this effect of methimazole has been limited by the absence of objective diagnosis of the liver condition or the inappropriate use of the Naranjo scale. We present the case of an elderly man with hyperthyroidism, gastritis, and epilepsy who developed liver damage after administration of multiple drugs. Key points from the case Considering the low sensitivity of the Naranjo scale in detecting rare reactions associated with liver damage, we used the Roussel-Uclaf Causality Assessment Method scale, with a finding of cholestatic jaundice hepatitis induced by methimazole. The patient's liver enzyme levels improved after discontinuation of methimazole. Main lessons learned Our case underlines the possible hepatoxicity associated with the use of methimazole. A review of the literature confirmed a selective hepatoxicity risk in individuals of Asian ethnicity, which has not been identified in Caucasian or Black populations. Physicians should be aware of the risk of hepatoxicity when prescribing oral methimazole to patients of Asian ethnicity.