[Effect of endonasal endoscopic dacryocystorhinostomy combined with lacrimal duct drainage tube implantation in treating lacrimal duct obstruction].

Objective:To investigate the clinical effect of endonasal endoscopic dacryocystorhinostomy（EES-DCR） combined with lacrimal duct drainage tube implantation in treating the patients with lacrimal duct obstruction. Methods: 32 patients （37 eyes） with lacrimal duct obstruction were included into this study, including 1 patient （2 eyes） of functional nasal lacrimal duct obstruction,2 patients （2 eyes） of recurrence after EES-DCR,17 patients （19 eyes） of nasal lacrimal duct obstruction,6 patients （8 eyes） of small lacrimal sac, and 6 patients （6 eyes） of lacrimal duct obstruction. Intraoperative EES-DCR was performed, and lacrimal drainage tubes were implanted from the upper and lower lacrimal points. Septoplasty was performed in 3 patients with nasal septum deviation, and endoscopic sinus surgery was performed in 1 patient with chronic sinusitis.After operation, nasal hormone spraying was performed. During follow-up, the operation effect was evaluated according to the degree of symptom improvement, the patency of lacrimal passage irrigation and the opening state of dacryocystorhinostomy under nasal endoscope. Results:After 3-30 months of follow-up, 29 cases（34 eyes） were cured, 2 cases（2 eyes） were improved, and 1 case（1 eye） was ineffective. The total effective rate was 97.3%（36/37）. No intraorbital, intracranial or nasal complications occurred in all patients. Conclusion:EES-DCR combined with lacrimal duct drainage tube implantation is safe and effective in treating lacrimal duct obstruction. Implantation of lacrimal duct drainage tube can effectively avoid stoma blockage, prevent the adhesion of lacrimal duct, and significantly improve the success rate of surgery.

Effects of MiR-194-5p on the proliferation and invasion of laryngeal cancer cells by regulating the expression of smurf1 and activating the mTOR signaling pathway.

Laryngeal cancer has become the focus of research because of its high incidence rate and mortality rate. However, the research on miR-194-5p in laryngeal cancer is quite rare. The purpose of this study is to explore the effect of miR-194-5p on the proliferation and invasion of laryngeal cancer cells in order to find an effective way to treat laryngeal cancer. The results showed that miR-194-5p could activate the mTOR signaling pathway by regulating the expression of Smurf1, which had an effect on laryngeal cancer cells. The results showed that the absorbance of the miR-194-5p group was 0.38 lower than that of the NC group, which indicated that up-regulation of mir-194-5p could weaken the proliferation of laryngeal cancer cells. In addition, the average number of laryngeal cancer cells in NC and the miR-194-5p groups was 125.2 and 53.8, respectively, which indicated that miR-194-5p could reduce the number of laryngeal cancer cells passing through the basement membrane and their invasion ability.

CEBPB knockdown sensitizes nasopharyngeal carcinoma cells to cisplatin by promoting the expression of serine protease inhibitor Kazal-type 5.

Serine protease inhibitor Kazal-type 5 (SPINK5) has been indicated to act as a prognostic predictor for patients with head and neck squamous cell carcinoma. However, its specific role in nasopharyngeal carcinoma (NPC), a malignancy that has a high propensity for chemoresistance, remains largely obscure. We, thus, sought to investigate the importance of SPINK5 expression in regulating chemoresistance in NPC. Differentially expressed genes in NPC were screened using the cancer genome atlas-head and neck squamous cell carcinoma database and microarray analysis. SPINK5 was downregulated in NPC tissues and cells. After SPINK5 upregulation, the cells treated with cisplatin showed reduced cell survival and the ability to migrate, invade and metastasize. Mechanistically, the transcription factors regulating SPINK5 were queried through the JASPAR website, followed by dual-luciferase and Chromatin immunoprecipitation assay validation. CCAAT enhancer-binding protein (CEBP) beta (CEBPB) bound to the SPINK5 promoter region in NPC cells. The silencing of CEBPB enhanced the expression of SPINK5. CEBPB overexpression reversed the inhibitory effects of cisplatin on NPC cell malignant phenotype in the presence of SPINK5 overexpression. In conclusion, CEBPB silencing promoted chemoresistance of NPC cells via activating SPINK5, signifying that targeting CEBPB was a new approach to enhance the chemotherapy efficacy in NPC.

Long Noncoding RNA MIAT Regulates the Process of Laryngeal Squamous Cell Carcinoma Through Regulation of miR-147a/BCOR.

BACKGROUND: Myocardial infarction associated transcript (MIAT) is a long non-coding RNA (lncRNA) that can play oncogenic role in different kinds of cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unknown. AIM: The study aimed to explore the effect of MIAT/miR-147a/BCOR axis on LSCC progression. METHODS: The expression pattern of MIAT, miR-147a and BCOR in LSCC samples and cells was identified through qRT-PCR. The proliferation of LSCC cells was assessed by colony formation assay and CCK-8 assays. Transwell assays were implemented to test the migratory and invasive abilities of LSCC cells. Proteins associated with migration and epithelial-mesenchymal transition were probed in transfected LSCC cells by western blot. The interaction of miR-147a with MIAT or BCOR was analyzed by luciferase reporter assays, RNA pulls down assays and Ago2-RIP assays. RESULTS: High MIAT expression was closely correlated with unfavorable prognosis. MIAT knockdown inhibited cell proliferation, migration, invasion and EMT progress in LSCC. MIAT acted as a miR-147a sponge to increase the expression of BCOR. Silencing of MIAT suppressed LSCC progression through miR-147a/BCOR axis. CONCLUSION: MIAT acts as an oncogene by controlling miR-147a/BCOR axis in LSCC.

A model of seven immune checkpoint-related genes predicting overall survival for head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease characterized by different molecular subtypes with different prognosis and response to treatment. Therefore, the aim of this study was to construct reliable gene signatures based on immune checkpoint-related genes to distinguish between subgroups of patients with different risks. METHODS: We obtained the HNSCC data from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) as a training set and the external validation set, respectively. First, differentially expressed immune checkpoint-related genes in tumor tissues and normal tissues were determined, and the potential functions of differential genes were explored through GO function annotation and KEGG pathway enrichment analysis. Using univariate Cox regression analysis, 20 immune checkpoint-related genes in HNSCC patients were significantly associated with overall survival (OS). Subsequently, seven genes were selected by multivariate Cox regression analysis to create a gene signature. Next, the stability of gene signatures was assessed using Kaplan-Meier curve, Time-dependent receiver operating characteristic (ROC) curve. Finally, we constructed a nomogram visualization modelled to facilitate subsequent clinical applications. RESULTS: A total of 80 differentially expressed genes (DEGs) were obtained, the GO analysis of these DEGs indicated that they were significantly enriched in positive regulation of cell activation, T cell activation; the KEGG analysis results performed and showed that the DEGs were enriched in the MAPK signaling pathway, PI3K - Akt signaling pathway. 7 genes (PPP2R1B, MYD88, CD86, CD80, MAP2K1, TRIB3 and ICOS) were screened by univariate and multivariate Cox regression, and they were used to construct a prognostic model. In the TCGA and GEO datasets, Kaplan-Meier analysis indicated that patients in the high-risk group have a poor prognosis. The sensitivity and specificity evaluation of prognostic model for 1-, 3-, 5-year OS in TCGA were 0.644, 0.661 and 0.625, respectively; and in GSE41613 were 0.748, 0.719, and 0.727, respectively. The calibration chart curve showed that the nomogram has strong clinical performance in the prognosis prediction of HNSCC patients. CONCLUSIONS: A novel immune checkpoint-related gene signature can effectively predict and stratify OS in HNSCC patients.

TIPE1-mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway.

Recent studies have shown that tumour necrosis factor-α-induced protein 8 like-1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1-overexpressing CNE-1 and CNE-2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1-overexpressing CNE-1 and CNE-2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.

Soyasapogenol B Attenuates Laryngeal Carcinoma Progression through Inducing Apoptotic and Autophagic Cell Death.

Soyasapogenol B (Soy B), a constituent of soybean, has been shown to exhibit antitumor activities against different types of cancers. However, to our knowledge, no studies so far have investigated the effect of Soy B in human laryngeal carcinoma. This study, therefore, aimed to determine the effect of Soy B in human laryngeal carcinoma cell lines HeP-2 and TU212 and to elucidate the possible underlying mechanisms by which Soy B can induce its antitumor effects. The results showed that Soy B effectively attenuated the cell growth by causing G0/G1 phase cell cycle arrest in laryngeal carcinoma cell lines. Moreover, the percentage of apoptotic and autophagic cells dramatically increased upon exposure to Soy B. Western blotting results confirmed that Soy B can alter the expression levels of established markers of apoptosis and autophagy. Interestingly, both apoptosis inhibitor (ZVAD-fmk) and autophagy inhibitor (3-MA) could partially reverse the effect of Soy B, while blocking autophagy did not cause obvious alteration in the percentage of apoptotic cells. Similarly, in vivo studies validated that Soy B could effectively reduce the size of the tumor and induce apoptosis and autophagy in tumor tissues. Collectively, these results suggested that Soy B can exert anticancer activities against laryngeal carcinoma through inducing apoptotic and autophagic cell death. Our study highlighted the potential role of Soy B as a chemotherapeutic agent for laryngeal carcinoma. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1851-1858, 2020. © 2019 American Association for Anatomy.

Role of the Akt/mTOR signaling pathway in human papillomavirus-associated nasal and sinonasal inverted papilloma.

Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface epithelial cells grow downward into the underlying supportive tissue with varying degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal agent in the pathogenesis of this disease. Many studies have shown that HPV can activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but the role of this pathway in HPV-associated NSIP is largely unknown. In this study, we enrolled 40 control tissue samples and 80 NSIP tissue samples. HPV genotyping showed that 47 of the 80 examined cases of NSIP were HPV-positive (58.8%), and the most common subtype was HPV11 (20/53, 37.7%). The immunohistochemistry showed statistically significant differences in phosphorylated Akt and phosphorylated S6 ribosomal protein staining among control samples, HPV-positive NSIP and HPV-negative NSIP. The HPV11 L1-L2 plasmid increased the proliferation of normal human nasopharyngeal epithelial NP69-SV40T cells and human nasopharyngeal cancer CNE1 cells. Meanwhile, rapamycin, an mTOR inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2 plasmid. Western blot analysis showed that Akt/mTOR/S6 were overexpressed in NP69-SV40T cells and CNE1 cells infected with the HPV11 L1-L2 plasmid. These data demonstrate that HPV promotes cell proliferation through the Akt/mTOR signaling pathway in NSIP.

Packing fractal Sierpinski triangles into one-dimensional crystals via a templating method.

Crystalline structures with Sierpinski triangles as building blocks were constructed via a templating method in an ultra-high vacuum and studied by low-temperature scanning tunneling microscopy. Cobalt atoms and 4,4''-dicyano-1,1':3',1''-terphenyl molecules were used to build the Sierpinski triangles. The Au(100)-(hex), Au(111)-22 ×, and stepped Au(111) surfaces were used as templates to guide the packing of Sierpinski triangles. One-dimensional double chains and two-dimensional small domains of Sierpinski triangles were successfully prepared using the method in experiments.

Charging single Co atoms on ultrathin NaCl films.

Single Co adatoms adsorbed on a double-layer NaCl film supported by Cu(111) were negatively charged after applying a positive voltage pulse to the sample in a scanning tunnelling microscope. Density functional calculations showed that the magnetic moment of Co changed from 3µB to 2.2µB after charge state manipulation.