Nicotine downregulates miR-375-3p via neurotrophic tyrosine receptor kinase 2 to enhance the malignant behaviors of laryngopharyngeal squamous epithelial cells.

Nicotine exposure from smoking constitutes a significant global public health concern. Furthermore, smoking represents a pivotal risk factor for head and neck squamous cell carcinoma (HNSCC). However, the influence of nicotine on HNSCC remains relatively underexplored. Our aim was to unravel the molecular mechanisms that underlie the effect of nicotine on the metastatic cascade of HNSCC. In this study, we discovered a significant association between smoking and HNSCC metastasis and prognosis. Nicotine significantly enhanced HNSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Analysis of TCGA-HNSCC and FDEENT-HNSCC cohorts revealed reduced miR-375-3p levels in HNSCC tumor tissues, particularly among current smokers. Additionally, miR-375-3p level was strongly correlated with both lymph node metastasis and tumor stage. By downregulating miR-375-3p, nicotine promotes HNSCC cell metastasis in vitro and hematogenous metastatic capacity in vivo. Utilizing transcriptomic sequencing, molecular docking, dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH), we demonstrated that miR-375-3p specifically binds to 3' untranslated region (3'UTR) of NTRK2 mRNA. Thus, this study uncovers a novel nicotine-induced mechanism involving miR-375-3p-mediated NTRK2 targeting, which promotes HNSCC metastasis. These findings have implications for improving the prognosis of patients with HNSCC, especially in smokers.

Fusobacterium nucleatum facilitates proliferation and autophagy by activating miR-361-3p/NUDT1 axis through oxidative stress in hypopharyngeal squamous cell carcinoma.

BACKGROUND: To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins. RESULTS: Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH-, which could be proven by H2O2 assay and N-acetylcysteine. CONCLUSIONS: Higher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.

Diagnostic and prognostic value of plasma cell-free DNA combined with VEGF-C in laryngeal squamous cell carcinoma.

BACKGROUND: Circulating cell-free DNA (cfDNA) and vascular endothelial growth factor-C (VEGF-C) can be utilized to detect cancer and predict its prognosis. However, their potential application in laryngeal squamous cell carcinoma (LSCC) is unclear. PURPOSE: This study aimed to identify the diagnostic and prognostic value of cfDNA and VEGF-C in LSCC patients. METHODS: The plasma cfDNA of 148 LSCC patients and 43 non-tumor patients were isolated. Quantitative real-time PCR (qRT-PCR) was performed to assess long and short DNA fragments in plasma by amplifying the ALU repeats. ALU-qPCR results (ALU247/ALU115) were used to calculate cfDNA integrity index. Vascular endothelial growth factor-C (VEGF-C) level was detected by ELISA assay. Correlation between cfDNA and clinical features was analyzed. For detecting the sensitivity and specificity of cfDNA and VEGF-C alone or in combination for diagnosing LSCC, receiver operator characteristic (ROC) was established. For evaluating the overall survival (OS) of LSCC, Kaplan-Meier curves were established. RESULTS: LSCC patients had significantly higher levels of plasma cfDNA (ALU115, ALU247, and cfDNA integrity index) and VEGF-C than those without cancer (p < 0.05), showing area under the curve (AUC) values of 0.79, 0.74, 0.62 and 0.80, when cutoff value was correspondingly defined at 2.14 ng/mL, 1.39 ng/mL, 0.73 and 412.90 pg/mL, respectively. The AUC for distinguishing LSCC patients from non-tumor patients by plasma cfDNA combined with VEGF-C was 0.89 (95% CI: 0.83-0.94). A significant correlation was found between plasma cfDNA levels and Ki-67, tumor size, pT stage, and smoking history (p < 0.05). Based on survival analysis, low VEGF-C concentration groups had longer OS than those with high VEGF-C concentration (p = 0.02). CONCLUSION: Indicators such as plasma cfDNA and VEGF-C may be used to diagnose and monitor LSCC for its noninvasiveness and rapid accessibility.

Clinical Efficacy and Safety of Early Intravenous Administration of Beta-Blockers in Patients Suffering from Acute ST-Segment Elevation Myocardial Infarction Without Heart Failure Undergoing Primary Percutaneous Coronary Intervention: A Study-Level Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Several clinical studies have produced diverse results regarding the efficacy and safety of early intravenous beta-blockers in patients with acute ST-segment elevation myocardial infarction (STEMI). A study-level meta-analysis of randomized clinical trials (RCTs) comparing early intravenous beta-blockers versus placebo or routine care in STEMI patients undergoing primary percutaneous coronary intervention (PCI) was performed. METHODS: A database search was conducted using PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov for randomized clinical trials (RCTs) that compared intravenous beta-blockers versus placebo or routine care in STEMI patients who underwent primary PCI. The efficacy outcomes were infarct size (IS, % of LV) and the myocardial salvage index (MSI) based on magnetic resonance imaging, electrocardiographic findings, heart rate, ST-segment reduction percent (STR%), and complete STR. Safety outcomes included arrhythmias in the first 24 h (ventricular tachycardia and fibrillation [VT/VF], atrial fibrillation [AF], bradycardia, and advanced atrioventricular [AV] block), cardiogenic shock and hypotension during hospitalization, left ventricular ejection fraction (LVEF), and major adverse cardiovascular events (cardiac death, stroke, reinfarction, and heart failure readmission) at follow-up. RESULTS: Seven RCTs with 1428 patients were included in this study, with 709 patients in the intravenous beta-blockers and 719 in the control group. Intravenous beta-blockers improved MSI compared to the control group (weighted mean difference [WMD] 8.46, 95% confidence interval [CI] 3.12-13.80, P = 0.002, I2 = 0%), but no differences were observed in IS (% of LV) between groups. Compared to the control group, the intravenous beta-blockers group had a lower risk of VT/VF (relative risk [RR] 0.65, 95% CI 0.45-0.94, P = 0.02, I2 = 35%) without an increase of AF, bradycardia, and AV-block and significantly decreased HR, hypotension. LVEF at 1 week ± 7 days (WMD 2.06, 95% CI 0.25-3.88, P = 0.03, I2 = 12%) and 6 months ± 7 days (WMD 3.24, 95% CI 1.54-4.95, P = 0.0002, I2 = 0%) was improved in the intravenous beta-blockers group compared to the control group. Subgroup analysis showed that intravenous beta-blockers before PCI decreased the risk of VT/VF and improved LVEF compared to the control group. Furthermore, sensitivity analysis showed that patients with a left anterior descending (LAD) artery lesion had a smaller IS (% of LV) in the intravenous beta-blockers group compared to the control group. CONCLUSION: Intravenous beta-blockers improved the MSI, decreased the risk of VT/VF in the first 24 h, and were associated with increased LVEF at 1 week and 6 months following PCI. In particular, intravenous beta-blockers started before PCI is beneficial for patients with LAD lesions.

Reversible Data Hiding in Encrypted Image Using Multiple Data-Hiders Sharing Algorithm.

Reversible Data Hiding in Encrypted Image (RDHEI) is a technology for embedding secret information in an encrypted image. It allows the extraction of secret information and lossless decryption and the reconstruction of the original image. This paper proposes an RDHEI technique based on Shamir's Secret Sharing technique and multi-project construction technique. Our approach is to let the image owner hide the pixel values in the coefficients of the polynomial by grouping the pixels and constructing a polynomial. Then, we substitute the secret key into the polynomial through Shamir's Secret Sharing technology. It enables the Galois Field calculation to generate the shared pixels. Finally, we divide the shared pixels into 8 bits and allocate them to the pixels of the shared image. Thus, the embedded space is vacated, and the generated shared image is hidden in the secret message. The experimental results demonstrate that our approach has a multi-hider mechanism and each shared image has a fixed embedding rate, which does not decrease as more images are shared. Additionally, the embedding rate is improved compared with the previous approach.

Dynamic Information-Hiding Method with High Capacity Based on Image Interpolating and Bit Flipping.

In this era of rapid information exchange in public networks, there is a risk to information security. Data hiding is an important technique for privacy protection. Image interpolation is an important data-hiding technique in image processing. This study proposed a method called neighbor mean interpolation by neighboring pixels (NMINP) that calculates a cover image pixel by neighbor mean interpolation and neighboring pixels. To reduce image distortion, NMINP limits the number of bits when embedding secret data, making NMINP have a higher hiding capacity and peak signal-to-noise ratio (PSNR) than other methods. Furthermore, in some cases, the secret data are flipped, and the flipped data are treated in ones' complement format. A location map is not needed in the proposed method. Experimental results comparing NMINP with other state-of-the-art methods show that NMINP improves the hiding capacity by more than 20% and PSNR by 8%.

2023 TAMIS/TSOC/TACVPR Consensus Statement for Patients with Acute Myocardial Infarction Rehabilitation.

Cardiac rehabilitation is a comprehensive intervention recommended in international and Taiwanese guidelines for patients with acute myocardial infarction. Evidence supports that cardiac rehabilitation improves the health-related quality of life, enhances exercise capacity, reduces readmission rates, and promotes survival in patients with cardiovascular disease. The cardiac rehabilitation team is comprehensive and multidisciplinary. The inpatient, outpatient, and maintenance phases are included in cardiac rehabilitation. All patients admitted with acute myocardial infarction should be referred to the rehabilitation department as soon as clinically feasible. Pre-exercise evaluation, including exercise testing, helps physicians identify the risks of cardiac rehabilitation and organize appropriate exercise prescriptions. Therefore, the Taiwan Myocardial Infarction Society (TAMIS), Taiwan Society of Cardiology (TSOC), and Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation (TACVPR) address this consensus statement to assist healthcare practitioners in performing cardiac rehabilitation in patients with acute myocardial infarction.

Fusobacterium nucleatum impairs DNA mismatch repair and stability in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Dysbiosis of the laryngeal microbiota has been demonstrated to the development of head and neck squamous cell carcinoma (HNSCC), but the association of Fusobacterium and Fusobacterium nucleatum (F. nucleatum) with DNA mismatch repair (MMR) and microsatellite instability (MSI) has not been investigated. METHODS: The abundance of Fusobacterium and F. nucleatum, the status of deficient MMR (dMMR) and MSI, and MMR-related gene expression were analyzed in 171 HNSCC tissues, 61 paired para-tumor tissues, and 60 vocal cord polyp tissues. The molecular mechanism of F. nucleatum and MMR-related gene expression were investigated in two human HNSCC cell lines (Tu 686 and FD-LSC-1). RESULTS: Our results demonstrated that a high Fusobacterium abundance was detected in the HNSCC tissues and was exaggerated in the recurrent patients. We further found that a high Fusobacterium abundance was detected in the HNSCC tissues with dMMR and MSI. The Fusobacterium abundance was negatively correlated with the expression of MLH1, MSH2, and MSH6 in the HNSCC tissues. The Fusobacterium abundance was closely associated with the F. nucleatum abundance in the HNSCC tissues. F. nucleatum increased miR-205-5p expression to suppress MLH1, MSH2, and MSH6 expression via the TLR4- and MYD88-dependent innate immune signaling pathway, resulting in dMMR, DNA damage, and cell proliferation in HNSCC. CONCLUSIONS: F. nucleatum impacts HNSCC epigenetic changes in tissues with dMMR to promote DNA damage and cell proliferation by suppressing MMR-related gene expression via the TLR4/MYD88/miR-205-5p signaling pathway, which is valuable in the development of efficient strategies for HNSCC prevention and treatment. LAY SUMMARY: This study clearly indicates that Fusobacterium induced head and neck squamous cell carcinoma (HNSCC) aggressiveness to affect poor prognosis in HNSCC patients by epigenetic alteration of DNA mismatch repair (MMR) and microsatellite instability. Moreover, the research has shown that Fusobacterium nucleatum ( F. nucleatum ) impacts HNSCC epigenetic changes in tissues with deficient MMR to promote DNA damage and cell proliferation by suppressing MMRrelated gene expression via the TLR4/MYD88/miR-205-5p signaling pathway.

Nervous Necrosis Virus Coat Protein Mediates Host Translation Shutoff through Nuclear Translocalization and Degradation of Polyadenylate Binding Protein.

Nervous necrosis virus (NNV) belongs to the Betanodavirus genus of the Nodaviridae family and is the main cause of viral nervous necrosis disease in marine fish larvae and juveniles worldwide. The NNV virion contains two positive-sense, single-stranded RNA genomes, which encode RNA-dependent RNA polymerase, coat protein, and B2 protein. Interestingly, NNV infection can shut off host translation in orange-spotted grouper (Epinephelus coioides) brain cells; however, the detailed mechanisms of this action remain unknown. In this study, we discovered that the host translation factor, polyadenylate binding protein (PABP), is a key target during NNV takeover of host translation machinery. Additionally, ectopic expression of NNV coat protein is sufficient to trigger nuclear translocalization and degradation of PABP, followed by translation shutoff. A direct interaction between NNV coat protein and PABP was demonstrated, and this binding requires the NNV coat protein N-terminal shell domain and PABP proline-rich linker region. Notably, we also showed that degradation of PABP during later stages of infection is mediated by the ubiquitin-proteasome pathway. Thus, our study reveals that the NNV coat protein hijacks host PABP, causing its relocalization to the nucleus and promoting its degradation to stimulate host translation shutoff. IMPORTANCE Globally, more than 200 species of aquacultured and wild marine fish are susceptible to NNV infection. Devastating outbreaks of this virus have been responsible for massive economic damage in the aquaculture industry, but the molecular mechanisms by which NNV affects its host remain largely unclear. In this study, we show that NNV hijacks translation in host brain cells, with the viral coat protein binding to host PABP to promote its nuclear translocalization and degradation. This previously unknown mechanism of NNV-induced host translation shutoff greatly enhances the understanding of NNV pathogenesis and provides useful insights and novel tools for development of NNV treatments, such as the use of orange-spotted grouper brain cells as an in vitro model system.

A novel signature derived from metabolism-related genes GPT and SMS to predict prognosis of laryngeal squamous cell carcinoma.

BACKGROUND: A growing body of evidence has suggested the involvement of metabolism in the occurrence and development of tumors. But the link between metabolism and laryngeal squamous cell carcinoma (LSCC) has rarely been reported. This study seeks to understand and explain the role of metabolic biomarkers in predicting the prognosis of LSCC. METHODS: We identified the differentially expressed metabolism-related genes (MRGs) through RNA-seq data of The Cancer Genome Atlas (TCGA) and Gene set enrichment analysis (GSEA). After the screening of protein-protein interaction (PPI), hub MRGs were analyzed by least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic signature. Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) was applied to verify the effectiveness of the prognostic signature in four cohorts (TCGA cohort, GSE27020 cohort, TCGA-sub1 cohort and TCGA-sub2 cohort). The expressions of the hub MRGs in LSCC cell lines and clinical samples were verified by quantitative reverse transcriptase PCR (qRT-PCR). The immunofluorescence staining of the tissue microarray (TMA) was carried out to further verify the reliability and validity of the prognostic signature. Cox regression analysis was then used to screen for independent prognostic factors of LSCC and a nomogram was constructed based on the results. RESULTS: Among the 180 differentially expressed MRGs, 14 prognostic MRGs were identified. A prognostic signature based on two MRGs (GPT and SMS) was then constructed and verified via internal and external validation cohorts. Compared to the adjacent normal tissues, SMS expression was higher while GPT expression was lower in LSCC tissues, indicating poorer outcomes. The prognostic signature was proven as an independent risk factor for LSCC in both internal and external validation cohorts. A nomogram based on these results was developed for clinical application. CONCLUSIONS: Differentially expressed MRGs were found and proven to be related to the prognosis of LSCC. We constructed a novel prognostic signature based on MRGs in LSCC for the first time and verified it via different cohorts from both databases and clinical samples. A nomogram based on this prognostic signature was developed.

Smoking-mediated nicotinic acetylcholine receptors (nAChRs) for predicting outcomes for head and neck squamous cell carcinomas.

BACKGROUND: As a human tumor disease, head and neck squamous cell carcinoma (HNSCC) is associated with a high mortality rate worldwide. Nicotinic acetylcholine receptors (nAChRs) are transmembrane receptor proteins and exert their biological effects following activation by nicotine. We aimed to construct a prognostic signature based on the expression of nAChRs among smokers with HNSCC. METHODS: The transcriptome profile of nAChRs was obtained from The Cancer Genome Atlas (TCGA). Following the integration of survival information, univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were performed to screen the prognosis-related nAChRs and construct a prognostic signature. Kaplan-Meier (KM), receiver operating characteristic (ROC), principal component analysis (PCA), and independent prognostic analysis were utilized to verify the predictive power of the nAChR-associated prognostic signature. The expression of α5 nAChR in clinical samples was verified by quantitative reverse transcriptase PCR. RESULTS: Subunits α2, α5, α9, and ß4 were related to the prognosis. The prognostic signature comprised the expression of subunits α5, α9, and ß4. The nAChR-associated signature showed high sensitivity and specificity for prognostic prediction and was an independent factor for overall survival. Based on the clinical variables and expression of nAChRs, a nomogram was constructed for predicting the outcomes of HNSCC patients who were smokers in the clinical settings. In clinical specimens, α5 nAChR showed high expression in HNSCC tissues, especially among smokers. CONCLUSIONS: The nAChR-associated signature constructed in this study may provide a better system for the classification of HNSCC patients and facilitate personalized treatment according to their smoking habits.

Oncologic outcomes of transoral laser microsurgery versus open partial laryngectomies in the management of early stage glottic carcinoma.

BACKGROUND: The oncologic outcomes between transoral laser microsurgery (TLM) and open partial laryngectomy (OPL) using comprehensive analysis in one clinical center is rare. The purpose of this study was to evaluate the oncologic outcomes of TLM in patients with early stage glottic carcinoma, and to compare the results with OPL. SUBJECTS AND METHODS: Records of 425 glottic carcinoma patients with T1 - T2 stage treated with TLM, vertical partial laryngectomy (VPL), and cricohyoidoepiglottopexy (CHEP) from 2005 to 2010 were retrospectively analyzed. The overall survival (OS), disease-specific survival (DSS), and laryngeal function preservation (LFP) of these three treatments were assessed. RESULTS: One hundred and twenty-two patients were treated with TLM. Regarding OPL, 167 patients underwent VPL, and 136 patients underwent CHEP. The mean age was 59.7 years, with men accounting for 97.2 % of all cases. The OS, DSS, and LFP rates of patients with anterior commissure (AC) involvement undergoing TLM were worse than those of patients without AC involvement, but these differences were not statistically significant. The 5-year OS, DSS, and LFP of patients undergoing TLM were 88.4 %, 89.9 %, and 83.5 %, respectively, and the oncologic outcomes of patients undergoing TLM, VPL, and CHEP were not statistically different. CONCLUSION: Glottic carcinoma patients with early stage treated with TLM experience satisfactory oncologic outcomes. No compelling difference in oncologic outcomes among three treatments of TLM, VPL and CHEP, as well as VPL and CHEP can be alternatives to patients who are not suitable for receiving TLM.

Preoperative tracheotomy in the treatment of upper airway obstruction of patients with advanced stage supraglottic carcinoma.

BACKGROUND: Preoperative tracheotomy is an effective option that secures upper airway patency in laryngeal carcinoma patients suffering from upper airway obstruction, but the influence of this treatment on oncologic outcomes of laryngeal carcinoma remains controversial. The purpose of this study was to determine the impact of preoperative tracheotomy on overall survival in supraglottic carcinoma patients with tumor obstruction of the upper airway, and explore the potential causes. MATERIALS AND METHODS: This retrospective study collected 243 consecutive patients with advanced stage supraglottic carcinoma from 2005 to 2010. Preoperative tracheotomy in the management of upper airway obstruction in patients with supraglottic carcinoma was analyzed. RESULTS: The mean age was 60.9 years at diagnosis, with men accounting for 98.4% of all patients. Thirty nine (16.0%) patients presenting with tumor obstruction of the upper airway required preoperative tracheotomy. T4 stage patients had higher rate of tracheotomy than those of patients with T3 stage (36.8% vs 12.2%). Patients with upper airway obstruction presented with greater tumor area compared with patients without (13.7 cm2 vs 9.0 cm2). The optimal cutoff value of tumor area for tracheotomy and OS rate were both at 10 cm2. Supraglottic patients with upper airway obstruction receiving preoperative tracheotomy had poorer OS rate compared with patients without. T stage and tumor area were correlated with upper airway obstruction, and these two variables were independent predictors of OS rate in supraglottic carcinoma patients. CONCLUSIONS: Advanced stage supraglottic carcinoma patients with upper airway obstruction undergoing preoperative tracheotomy experienced worse overall survival. Advanced T stage and greater tumor size were associated with upper airway obstruction, indicating that the negative influence of tumor obstruction on survival may be cause by these two preoperative variables. Therefore, preoperative tracheotomy acts only as an alternative procedure, and is not a prognostic agent.

An Efficient Authenticated Key Agreement Scheme Supporting Privacy-Preservation for Internet of Drones Communications.

In recent years, due to the rapid development of Internet of things (IoTs), various physical things (objects) in IoTs are smart enough to make their own decisions without the involvement of humans. The smart devices embedded in a drone can sense, collect, and transmit real-time data back to the controller from a designated environment via wireless communication technologies. The mobility, flexibility, reliability and energy efficiency of drones makes them more widely used in IoT environments such as commercial, military, entertainment applications, traffic surveillance and aerial photography. In a generalized IoD architecture, we have communications among the drones in a flying zone, among the drones and the control server, and also among the drones and authorized user. IoD still has many critical issues that need to be addressed, such as data access being carried out through a public channel and battery operated drones. To address these concerns in IoD communications, in this paper, an efficient authentication and secure communication scheme with privacy preservation is proposed and it only uses secure one-way hash function and bitwise XOR operations when control server, drone and user mutually authenticate each other. After the successful authentication, both IoD-based participants can agree on a common session key to secure the subsequent communication messages. The widely accepted ProVerif and BAN logic analysis have been used to assure that the proposed scheme is provably secure against existing well-known security attacks and ensures privacy. Finally, a comparative analysis is presented to demonstrate the proposed scheme preserves efficiency when compared to existing competitive schemes.

Oropharynx microbiota transitions in hypopharyngeal carcinoma treatment of induced chemotherapy followed by surgery.

AIMS: To analyze changes in oropharynx microbiota composition after receiving induced chemotherapy followed by surgery for hypopharyngeal squamous cell carcinoma (HPSCC) patients. METHODS: Clinical data and swab samples of 38 HPSCC patients (HPSCC group) and 30 patients with benign disease (control group, CG) were enrolled in the study. HPSCC group was stratified into two groups: induced chemotherapy group (IC) of 10 patients and non-induced chemotherapy group (nIC) of 28 patients. The microbiota from oropharyngeal membrane was analyzed through 16S rRNA sequencing. RESULTS: Alpha-diversity (Shannon and Ace indexes) and weighted UniFrac based beta-diversity severely decreased in the HPSCC group when compared with CG. In pre-operative comparisons, PCoA and NMDS analyses showed microbial structures in the IC group were more similar to CG than nIC. Both IC group and nIC group yielded significantly diverse post-operative communities in contrast to their pre-operative counterparts, evident by the decrease in genera Veillonella and Fusobacterium and increase in genera Streptococcus and Gemella. Given that post-operative oropharynx microbiota showed no difference between IC and nIC groups, the IC group showed less accumulation in anaerobic communities. The abundance of genera Fusobacterium, Parvimonas, Actinomyces were enhanced in the advanced stages (III/IV). CONCLUSIONS: Oropharynx microbiota in the HPSCC group presents dysbiosis with low diversity and abundance. Induced chemotherapy is beneficial in adjusting the oropharynx microbial environment leading to fewer amounts of anaerobe accumulation after operation. Higher amounts of Fusobacterium in advanced stages (III/IV) may influence the progression of HPSCC.

miR-17-5p drives G2/M-phase accumulation by directly targeting CCNG2 and is related to recurrence of head and neck squamous cell carcinoma.

BACKGROUND: The human miR-17-92 polycistron is the first reported and most well-studied onco-miRNA with a cluster of seven miRNAs. miR-17-5p, a member of the miR-17-92 family, plays an important role in tumor cell proliferation, apoptosis, migration and invasion. However, few studies have shown the role of miR-17-5p in the cell cycle of head and neck squamous cell carcinoma (HNSCC). METHODS: RT-qPCR was used to detect miR-17-5p expression levels in 64 HNSCC tissues and 5 cell lines. The relationship between the expression of miR-17-5p in the tissues and the clinical characteristics of the patients was analyzed. HNSCC cells were transfected with an miR-17-5p mimic or inhibitor to evaluate cell cycle distribution by flow cytometry. Cell cycle distribution of cells transfected with target gene was evaluated using flow cytometry. Dual-luciferase reporter assay was used to detect the regulatory effect of miR-17-5p on target gene expression. RESULTS: In the present study, we found that miR-17-5p expression in HNSCC tissues and cell lines was remarkably increased, and miR-17-5p is related to recurrence in HNSCC patients. Silencing miR-17-5p blocked HNSCC cells in G2/M phase, whereas its overexpression propelled cell cycle progression. More importantly, we verified that miR-17-5p negatively regulated CCNG2 mRNA and protein expression by directly targeting its 3'UTR. CONCLUSION: These findings suggest that miR-17-5p might act as a tumor promoter and prognostic factor for recurrence in HNSCC patients.

Prognostic value of pathological tumor size in patients with supraglottic carcinoma.

BACKGROUND: The association between pathological tumor size and predictive value in patients with supraglottic carcinoma who receive surgery is poorly understood. To gain further insight into this association, the influence of postoperative tumor size assessed via pathological evaluation on survival outcomes in patients with supraglottic carcinoma was fully analyzed. MATERIALS AND METHODS: This study collected data from 375 consecutive supraglottic carcinoma patients who underwent primary surgical treatment between 2005 and 2010. The parameters of tumor size, including tumor diameter, tumor area, and tumor volume, were used to analyze the prognostic abilities of overall survival (OS) and disease-free survival (DFS) in supraglottic carcinoma. RESULTS: Twelve women and 363 men were included, with a mean age of 61.2 years. The 5-year OS and DFS rates were 65.4% and 56.2%, respectively. The mean tumor diameter, tumor area, and tumor volume of all patients was 3.1 cm, 8.6 cm2, and 9.1 cm3, respectively. Tumors with higher pT stages had a larger tumor diameter, tumor area, and tumor volume. These three factors were significantly correlated with pT stage, and tumor volume was the strongest factor contributing to pT stage. Patients with a larger tumor diameter, tumor area, and tumor volume had worse OS and DFS. Tumor area and tumor volume were independent prognostic factors of OS and DFS in supraglottic carcinoma patients. CONCLUSIONS: Patients with a larger tumor size have inferior survival outcomes, and tumor area and tumor volume are independent predictive parameters of survival in supraglottic carcinoma patients who are treated with primary surgery.

A nomogram for predicting occult lymph node metastasis in early hypopharyngeal cancer with cN0.

PURPOSE: To explore the risk factors of cervical occult lymph node metastasis (OLNM) in early cN0 hypopharyngeal squamous cell carcinoma (HPSCC), and construct a nomogram model to predict the risk of OLNM in patients with early cN0 HPSCC. METHODS: 78 cases of early (T1-T2) HPSCC patients who underwent hypopharyngectomy were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine independent risk factors and a nomogram was constructed according to the results of the multivariate logistic regression analysis. Model performance was assessed by constructing a receiver operating characteristic (ROC) curve, and discriminatory capacity assessed using the area under the curve (AUC). Calibration was completed using a plotted calibration curve accompanied by the Hosmer-Lemeshow test. RESULTS: Multivariate logistic regression analysis revealed that age (OR 0.928, 95% CI 0.863-0.997), history of drinking (OR 6.668, 95% CI 1.724-25.788), histological differentiation of tumor (OR 7.269, 95% CI 1.000-52.820), depth of invasion (OR 5.046, 95% CI 1.281-19.874) were independent risk factors of OLNM in early cN0 HPSCC. The ROC curve had an AUC of 0.811 (95% CI 0.713-0.909), which implies good discriminate capacity. The calibration curve and the Hosmer-Lemeshow test (P = 0.972) demonstrated good model fitted and high calibration. CONCLUSION: A nomogram model based on age, drinking history, histological differentiation of tumor, and depth of tumor invasion was successfully developed to predict occult cervical lymph node metastasis in patients with early cN0 hypopharyngeal cancer.

Preoperative tracheotomy as reflection of tumor size impacting oncologic outcomes of patients with advanced stage glottic carcinoma.

PURPOSE: The aim of this study was to evaluate the influence of preoperative tracheotomy on oncologic outcomes of advanced stage glottic carcinoma patients, and to explore the potential reason. METHODS: We retrospectively analyzed 413 consecutive advanced stage glottic carcinoma patients from January 2005 to December 2010. The correlation of preoperative tracheotomy and potential impacting factor of tumor size involving tumor diameter and tumor area with overall survival (OS) and disease-free survival (DFS) was fully assessed. RESULTS: Our cohort consisted of 302 (73.1%) patients with T3 and 111 (26.9%) patients with T4, and 98 (23.7%) patients received preoperative tracheotomy. The OS and DFS rates of patients receiving preoperative tracheotomy were worse than those without (5-year OS: 49.3% versus 69.8%; 5-year DFS: 45.3% versus 61.0%). The mean tumor diameter and tumor area of patients with preoperative tracheotomy were greater than those without (3.3 cm versus 2.4 cm, 8.9 cm2 versus 4.7 cm2). The optimal cutoff values of tumor diameter and tumor area for tracheotomy were 2.85 cm and 6.64 cm2. Tumor diameter and tumor area were correlated with tracheotomy intervention. Furthermore, when considering the potential effect of tumor area in multivariate model, we found that it was a significant factor in survival outcomes but variable of preoperative tracheotomy was not. CONCLUSION: This study indicates that tumor size is correlated with preoperative tracheotomy, and tracheotomy intervention may be reflection from effect of great tumor size that is a true adverse factor influencing oncologic outcomes of advanced stage glottic carcinoma patients.

Nitrogen Functionalities of Amino-Functionalized Nitrogen-Doped Graphene Quantum Dots for Highly Efficient Enhancement of Antimicrobial Therapy to Eliminate Methicillin-Resistant Staphylococcus aureus and Utilization as a Contrast Agent.

There is an urgent need for materials that can efficiently generate reactive oxygen species (ROS) and be used in photodynamic therapy (PDT) as two-photon imaging contrast probes. In this study, graphene quantum dots (GQDs) were subjected to amino group functionalization and nitrogen doping (amino-N-GQDs) via annealing and hydrothermal ammonia autoclave treatments. The synthesized dots could serve as a photosensitizer in PDT and generate more ROS than conventional GQDs under 60-s low-energy (fixed output power: 0.07 W·cm-2) excitation exerted by a 670-nm continuous-wave laser. The generated ROS were used to completely eliminate a multidrug-resistant strain of methicillin-resistant Staphylococcus aureus (MRSA), a Gram-positive bacterium. Compared with conventional GQDs, the amino-N-GQDs had superior optical properties, including stronger absorption, higher quantum yield (0.34), stronger luminescence, and high stability under exposure. The high photostability and intrinsic luminescence of amino-N-GQDs contribute to their suitability as contrast probes for use in biomedical imaging, in addition to their bacteria tracking and localization abilities. Herein, the dual-modality amino-N-GQDs in PDT easily eliminated multidrug-resistant bacteria, ultimately revealing their potential for use in future clinical applications.