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Epithelial-mesenchymal transition (EMT) is an important characteristic in the remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). IL-36γ and fibroblast activation protein (FAP) may exacerbate remodeling in CRS. Here, we aimed to determine whether IL-36γ and FAP expression are associated with EMT and may be a predictor for CRSwNP prognosis.52 non-Eos CRSwNP patients and 12 control patients were obtained and were followed up for more than 1 year after surgery. IL-36γ, FAP and EMT markers expression were evaluated by real-time polymerase chain reaction and western-blot. Masson trichrome staining was adopted to assess tissue fibrotic changes. Furthermore, the soluble form of IL-36γ and FAP in nasal secretions were detect by ELISA.While basal expression of E-cadherin decreased, the expression of IL-36γ, vimentin and FAP increased in nasal polyps. In well prognosis patients, the expression of IL-36γ, vimentin and FAP were significantly decreased than in poor prognosis patients, while the protein expression of E-cadherin was increased. The protein expression of IL-36γ was notably increased in recurrent nasal polyps than in preoperation specimens. A positive relationship between IL-36γ and FAP expression, a negative relationship between IL-36γ and E-cad expression was noted. The soluble form of IL-36γ and FAP increased during the development of non-Eos CRSwNP, with the highest level in poor prognosis patients after surgery.Non-Eos CRSwNP have partially undergone EMT under baseline conditions. IL-36γ and FAP expression were related with EMT, the soluble form of IL-36γ and FAP in nasal-secretions may predict the prognosis of patients.

PurposeThe COVID-19 pandemic has accelerated the process of teleworking and teleworking is expected to be a central feature of workplaces of the future. The present study examines the effect of leader-member exchange (LMX) and perception of loneliness on the relationship between proactive coping and the work productivity of teleworkers during the COVID-19 crisis time.Design/methodology/approachUsing structural equation modeling (SEM), this study the study is based on a survey of 572 teleworkers in Taiwan drawn from a variety of industry sectors.FindingsThrough the application of a hypothesized moderated mediation model, the indirect effects of proactive coping on work productivity via LMX are stronger for employees who experience a higher level of perceived loneliness.Research limitations/implicationsThe results have contributed to current understanding on the success of telework at the individual level and extends research framework of teleworking. Using self-report questionnaire is one of the limitations; however, this was feasible data collection method during COVID-19.Practical implicationsOrganizations need to provide further training aimed at enhancing proactive coping and dealing with future work challenges in the complex and dynamic workplace.Originality/valueThis study is the first among its type to examine proactive coping and job productivity from a LMX during COVID-19.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of

Key points:  Diagnosis of AIFRS should be alert in the immunocompromised patient presenting with new-onset, rapidly progressive sinusitis with facial-cranio-orbital spread.  Extended debridement should be considered on a case-by-case basis.  Antifungal agent contributed greatly to the outcome of AIFRS.  Prognosis mostly up to the balance of underlying disease and fungal invasion, more emphasizes should be focused on comprehensive treatment.  AIFRS with facial-cranio-orbital involved often had a disastrous end.

Purpose We investigated the role of Glut-1 and H+/K+-ATPase expression in pepsin-induced development of human vocal cord leukoplakia cells (HVCLCs). Next, we analyzed the relationship between Glut-1 and H+/K+-ATPase expression with the clinicopathological features of laryngeal carcinoma. Methods Glut-1 and H+/K+-ATPase expression levels in HVCLCs were determined after treatment with artificial gastric juice containing pepsin and laryngeal carcinoma tissues. Results Exposure to pepsin-containing artificial gastric juice significantly enhanced the migration and proliferation of VSCLCs in a time-dependent manner. The apoptotic rate of VSCLCs decreased over time after exposure to pepsin and reached a nadir on day 7 (p p +/K+-ATPase α, β significantly increased in HVCLCs compared to in the absence of pepsin (p +/K+-ATPase α, β gradually increased from vocal cord leukoplakia (VLC) to laryngeal carcinoma (p p p p Conclusions Elevated Glut-1 expression may promote the development of VCL by upregulating laryngeal H+/K+-ATPase expression to reactivate absorbed pepsin, thus damaging the laryngeal mucosa.

Purpose The purpose of this study is to explore the critical factors that affect users’ acceptance and usage intention toward blockchain-based smart lockers. Design/methodology/approach The research is designed in two phases. In the first phase, the key stakeholders are interviewed. Participants include managers from technology providers and logistics companies. In the second phase, a questionnaire survey is used to validate the proposed model. Findings Based on the final results, this study makes the following three suggestions. First, perceived usefulness and perceived ease of use are the critical factors. In other words, it is important to emphasize the function and convenience of a new service when introducing it to a potential user. Second, safety is not the major concern when using a blockchain-based smart locker. This means that users will trust the service provider for providing a secure service. Users do not worry about the security problem. Finally, the network externality of smart locker is also insignificant. Originality/value This study has three major contributions. First, this study identifies the critical factors that will affect user acceptance of blockchain-based smart lockers. Next, this study combines the opinions from service providers and users to understand the gap between different stakeholders. Finally, this study can enrich our understanding on the applications of blockchain from a managerial perspective and not only from a technical perspective, as in most previous studies.

Background Glucose transporter (GLUT)-mediated glucose uptake is an important process in the development of laryngeal carcinoma, one of the most common malignancies of the head and neck. GLUT-1, together with HIF-1α, is also an indicator of hypoxia. Both proteins play a critical role in glucose uptake and glycolysis in laryngeal carcinoma cells under hypoxic stress. A double gene knockout model in which HIF-1α and GLUT-1 are no longer expressed can provide important information about carcinogenesis in laryngeal carcinoma. Purpose In this study we used the CRISPR/Cas 9 system to induce HIF-1α and GLUT-1 double gene knockout in HEp-2 cells and then used the knocked-out cells to study the role of these markers in laryngeal carcinoma, including in chemoradioresistance. Methods High-grade small-guide RNAs (sgRNAs) of HIF-1α and GLUT-1 were designed using an online tool and inserted into the pUC57-T7-gRNA vector. The recombinant plasmids were transfected into HEp-2 cells and positive cells were screened using the dilution method. Gene mutation and expression were determined by sequence analysis and immunoblotting. Results In HIF-1α and GLUT-1 double gene knockout HEp-2 cells, a 171-bp deletion in the HIF-1α genomic sequence was detected, whereas multiple base insertions resulted in frameshift mutations in the GLUT-1 gene. Neither HIF-1α nor GLUT-1 protein was expressed in positive cells. The proliferation, migration, and invasion of HEp-2 cells were significantly decreased afterward. The possible mechanism may be that the inhibition PI3K/AKT/mTOR pathway by HIF-1α and GLUT-1 double gene knockout using CRISPR/Cas9 technique lead to reduction of glucose uptake and lactic acid generation. Conclusion Our HIF-1α and GLUT-1 double gene knockout HEp-2 cell model, obtained using a CRISPR/Cas9-based system, may facilitate studies of the pathogenesis of laryngeal carcinoma.

In this study, we investigated the ability of curcumin alone or in combination with GLUT1 siRNA to radiosensitize laryngeal carcinoma (LC) through the induction of autophagy. Protein levels in tumour tissues and LC cells were measured by immunohistochemistry and Western blotting. In vitro, cell proliferation, colony formation assays, cell death and autophagy were detected. A nude mouse xenograft model was established through the injection of Tu212 cells. We found that GLUT1 was highly expressed and negatively associated with autophagy-related proteins in LC and that curcumin suppressed radiation-mediated GLUT1 overexpression in Tu212 cells. Treatment with curcumin, GLUT1 siRNA, or the combination of the two promoted autophagy. Inhibition of autophagy using 6-amino-3-methypourine (3-MA) promoted apoptosis after irradiation or treatment of cells with curcumin and GLUT1 siRNA. 3-MA inhibited curcumin and GLUT1 siRNA-mediated non-apoptotic programmed cell death. The combination of curcumin, GLUT1 siRNA and 3-MA provided the strongest sensitization in vivo. We also found that autophagy induction after curcumin or GLUT1 siRNA treatment implicated in the AMP-activated protein kinase-mTOR-serine/threonine-protein kinase-Beclin1 signalling pathway. Irradiation primarily caused apoptosis, and when combined with curcumin and GLUT1 siRNA treatment, the increased radiosensitivity of LC occurred through the concurrent induction of apoptosis and autophagy.

This study examines the relationship between proactive coping, future time orientation, and perceived work productivity during the coronavirus (COVID-19) pandemic, based on the work-from-home experience of employees in Taiwan and the United States (U.S.). It draws on the conservation of resources (COR) theory, which posits that proactive coping and future time orientation are crucial personal resources that affect the capacity of an individual to adapt to stressful situations. The results show that in the relationship between proactive coping and perceived work productivity, future time orientation acts as a full mediator in Taiwan and a partial mediator in the U.S. The study extends the application of the COR theory to the context of the COVID-19 pandemic and offers important insights that will enable professionals to assess the role of proactive coping and future time orientation in their productivity evaluations of working tasks and to design appropriate training sessions., Highlights • Telecommuting experiences of two samples were examined during COVID-19. • Proactive coping is positively associated with future time orientation and productivity. • Future time orientation served as an important mediator. • Mediating effect was different in two cultural samples. • Eastern cultural sample reported stronger links between examined constructs.

Systemic inflammation via host-tumor interactions is currently recognized as the seventh cancer hallmark. The purpose of this study was to detect whether pretreatment peripheral indexes were associated with aggressive behavior and prognosis of laryngeal carcinoma patients.The pretreatment peripheral indexes such as albumin and systematic immune-inflammation index (SII) in 338 patients with laryngeal carcinoma were retrospectively recorded, the relationships between them and clinicopathological features and prognosis were analyzed.A high SII value was significantly positively associated with age (Pretreatment peripheral indexes SII and albumin could function as inexpensive indicators of aggressive behavior and be feasible and promising predictive biomarkers for prognosis in laryngeal carcinoma patients. Quantification of pretreatment SII and albumin may help physicians to design more effective management and follow-up strategies in laryngeal carcinoma patients.

Purpose: Although the alteration of tumor immunity after radiotherapy (RT) has been studied widely in recent years, how radiotherapy mediates tumor immunity and whether glycolysis is involved in the mediation in hypopharyngeal cancer are still unclear. This study aimes to determine whether radiotherapy regulates programmed cell death ligand 1( PD-L1) partly via glucose transporter 1(GLUT-1) expression and whether PD-L1 expression predicts overall survival (OS) in patients with hypopharyngeal cancer. Methods: PD-L1, Glut-1 expression and C D4+, CD8+ T cell were detected by immunohistochemistry analysis on 47 pre-RT and 25 post-RT specimens of hypopharyngeal cancer. The changes of these indicators before and after radiotherapy were compared, and their association with overall survival of patients were analyzed. Moreover, we used siRNA-GLUT-1 to inhibit GLUT-1 expression and determined whether GLUT-1 was a key factor involved in mediation of PD-L1 expression by RT in vitro. Results: In multivariate analysis, patients with higher PD-L1 expression (P=0.037), higher CD4+ T cell infiltration (P=0.016) and earlier clinical stage (P=0.019) had favourable OS. The PD-L1 expression and CD4+, CD8+ T cell increased significantly after RT. PD-L1 expression was correlated with Glut-1 in pre-RT (P=0.002), but not after-RT(P=0.051). The PD-L1 expression of FaDu cells was upregulated after RT, especially at 96h after RT in vitro. However, the PD-L1 expression of siRNA-GLUT-1 FaDu cells was significantly decreased at 96h after RT when compared with FaDu cells. Conclusion: The patients with high PD‑L1 expression and CD4+ T cell infiltration might have favourable OS in hypopharyngeal cancer. RT could increase PD-L1 expression and alter tumor immunity, the expression of PD-L1 was correlated with Glut-1, and inhibiting GLUT-1 expression might decrease the expression of PD-L1. GLUT-1 might participate in the alteration of tumor immunity after RT.

Radiotherapy is one of the main methods for tumor treatment, with the improved radiotherapy delivery technique to combat cancer, there is a growing interest for finding effective and feasible ways to predict tumor radiosensitivity. Based on a series of changes in metabolism, microvessel density, hypoxic microenvironment, and cytokines of tumors after radiotherapy, a variety of radiosensitivity detection methods have been studied. Among the detection methods, positron emission tomography-computed tomography (PET/CT) is a feasible tool for response evaluation following definitive radiotherapy for cancers with a high negative predictive value. The prognostic or predictive value of PET/CT is currently being studied widely. However, there are many unresolved issues, such as the optimal probe of PET/CT for radiosensitivity prediction, the selection of the most useful PET/CT parameters and their optimal cut-offs such as total lesion glycolysis (TLG), metabolic tumor volume (MTV) and standardized uptake value (SUV), and the optimal timing of PET/CT pre-treatment, during or following RT. Different radiosensitivity of tumors, modes of radiotherapy action and fraction scheduling may complicate the appropriate choice. In this study, we will discuss the diverse methods for evaluating radiosensitivity, and will also focus on the selection of the optimal probe, timing, cut-offs and parameters of PET/CT for evaluating the radiotherapy response.

Background We investigated the relationships between glucose transporter protein-1 (GLUT-1) and hypoxia inducible factor-1α (HIF-1α) expression, 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) uptake and prognosis in laryngeal and hypopharyngeal carcinomas patients. Methods Levels of GLUT-1 and HIF-1α proteins were examined by immunohistochemistry in 55 patients with laryngeal and hypopharyngeal carcinomas. All patients underwent 18F-FDG positron emission tomography-computed tomography (PET/CT) before surgery. Results Levels of GLUT-1 and HIF-1α in laryngeal and hypopharyngeal carcinomas were significantly higher than in vocal cord polyps. GLUT-1 expression was correlated with HIF-1α expression (r=0.571, P

Background This study is to explore the role of curcumin and GLUT-1 antisense oligodeoxynucleotides (AS-ODN) on autophagy modulation-initiated radiosensitivity. Methods BALB/c mice were employed to establish xenograft model using Tu212 cell. The expression of autophagy- and apoptosis-related proteins was determined by WB. Autophagosome was observed under transmission electron microscope. Apoptosis of tumor tissue were detected by TUNEL staining. Results Combinations of curcumin and GLUT-1 AS-ODN with 10 Gy inhibited the tumor growth by inducing apoptosis of laryngeal cancer cells followed with the enhancement of autophagy. 3-MA also had a promotion effect on irradiation-mediated growth inhibition possibly by depressing PI3K and on curcumin/GLUT-1 AS-ODN-mediated growth inhibition potentially by regulating autophagic events. Of note, a de-escalation of radiotherapy dose (5 Gy) along with curcumin, GLUT-1 AS-ODN or 3-MA produced a stronger effect than high dosage of radiotherapy (10 Gy) alone. Conclusions Curcumin and GLUT-1 AS-ODN improve the radiosensitivity of laryngeal carcinoma through regulating autophagy and inducing apoptosis.

Background Glucose transporter (GLUT)-mediated glucose uptake is an important process in the development of laryngeal carcinoma, one of the most common malignancies of the head and neck. GLUT-1, together with HIF-1α, is also an indicator of hypoxia. Both proteins play a critical role in glucose uptake and glycolysis in laryngeal carcinoma cells under hypoxic stress. A double gene knockout model in which HIF-1α and GLUT-1 are no longer expressed can provide important information about carcinogenesis in laryngeal carcinoma. Purpose In this study we used the CRISPR/Cas 9 system to induce HIF-1α and GLUT-1 double gene knockout in HEp-2 cells and then used the knocked-out cells to study the role of these markers in laryngeal carcinoma, including in chemoradioresistance. Methods High-grade small-guide RNAs (sgRNAs) of HIF-1α and GLUT-1 were designed using an online tool and inserted into the pUC57-T7-gRNA vector. The recombinant plasmids were transfected into HEp-2 cells and positive cells were screened using the dilution method. Gene mutation and expression were determined by sequence analysis and immunoblotting. Results In HIF-1α and GLUT-1 double gene knockout HEp-2 cells, a 171-bp deletion in the HIF-1α genomic sequence was detected, whereas multiple base insertions resulted in frameshift mutations in the GLUT-1 gene. Neither HIF-1α nor GLUT-1 protein was expressed in positive cells. The proliferation, migration, and invasion of HEp-2 cells were significantly decreased afterward. The possible mechanism may be that the inhibition PI3K/AKT/mTOR pathway by HIF-1α and GLUT-1 double gene knockout using CRISPR/Cas9 technique lead to reduction of glucose uptake and lactic acid generation. Conclusion Our HIF-1α and GLUT-1 double gene knockout HEp-2 cell model, obtained using a CRISPR/Cas9-based system, may facilitate studies of the pathogenesis of laryngeal carcinoma.

Branchial cleft anomalies are the second most common head and neck congenital lesions in children. It may sometimes be a part of branchio-oto-renal (BOR) syndrome, so in patients with branchial cleft anomalies associated with a complaint of auricular deformity or a similar history and findings in other family members, we should take an additional examination to find the possibility of BOR syndrome. Complete excision is essential for good prognosis. For the management of branchial cleft anomalies, various methods have been reported. Endoscopically assisted dissection technique and transoral robot-assisted surgery were used in the management of fistula and allowed excellent visualization of the pharyngeal component of the lesion and a minimally invasive approach. It is essential for the surgeon to fully comprehend the congenital lesions to attain the correct preoperative diagnosis and plan for an appropriate surgical approach to prevent the most common complication and recurrence in these lesions. The following sections discuss the anatomy, common presentation, auxiliary examination, differential diagnosis, the current principles of surgical treatment and prognosis for second branchial cleft anomalies in children, and discussed the branchio-oto-renal syndrome.

Rationale: Basal cell adenoma (BCA) is a rare benign salivary gland tumor. It is difficult to be completely resected when arising in parapharyngeal space. A contemporary trend is to develop minimally invasive approaches on the premises of safety and complete resection. Patient concerns: Three patients were referred to our ENT Outpatient Department with the chief complaint of an uncomfortable throat. CT or MRI revealed a unilateral mass in the parapharyngeal space, round or oval in shape, with well-defined borders. Diagnoses: CT and MRI provided useful information for the preoperative evaluation. The appearance of large-scale cystic components may be an important clue for the diagnosis of BCA. PET/CT images were also available in one case. The final diagnoses were all basal cell adenomas (tubular type) in parapharyngeal space according to the regular histopathological examination after surgery. Interventions: All three cases were completely resected by a trans-oral approach. The average operative time and estimated blood loss were 86 (range, 61–106) min and 116.7 (range, 50–200) mL, respectively. Endoscopy was used in the largest case to further assess the residual cavity after the complete resection and hemostasis. Outcomes: Postoperative recovery courses were quick and uneventful, with no neurovascular complication. Patients were discharged on the 3rd–5th day after surgery on an oral diet. One patient reported symptoms of velopharyngeal incompetence, manifested as mild slurred speech and nighttime salivation, for up to 3 months, which recovered spontaneously thereafter. There was no evidence of recurrence in the follow-up period. Lessons: In our experience, the trans-oral approach appeared to be effective, safe, and less invasive for extirpation of selected basal cell adenomas in the parapharyngeal space. An assistance of endoscopy facilitates the surgery.

// Li-Fang Shen 1 , Xin Zhao 2 , Shui-Hong Zhou 1 , Zhong-Jie Lu 3 , Kui Zhao 2 , Jun Fan 4 , Min-Li Zhou 1 1 Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China 2 Center of PET/CT, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China 3 Department of Radiotherapy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China 4 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China Correspondence to: Shui-Hong Zhou, email: zhouyunzhoush@163.com Keywords: hypoxia-inducible factor 1α, glucose transporter-1, antisense oligodeoxynucleotides, radiosensitivity, 18 F-FDG micro PET/CT Received: November 04, 2016 Accepted: March 15, 2017 Published: March 29, 2017 ABSTRACT Purpose: Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2′-deoxy-2’-[18F]fluoro-D-glucose ( 18 F-FDG) uptake and whether 18 F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo . Materials and Methods: To verify the above hypotheses, an in vivo model was applied by subcutaneously injecting Hep-2 (2 × 107/mL × 0.2 mL) and Tu212 cells (2 × 107/mL × 0.2 mL) into nude mice. The effects of HIF-1α antisense oligodeoxynucleotides (AS-ODNs) (100 μg) and GLUT-1 AS-ODNs (100 μg) on the radiosensitivity of laryngeal carcinoma were assessed by tumor volume and weight, microvessel density (MVD), apoptosis index (AI) and necrosis in vivo based on a full factorial (2 3 ) design. 18 F-FDG-PET/CT was taken before and after the treatment of xenografts. The relationships between HIF-1α and GLUT-1 expression and 18 F-FDG uptake in xenografts were estimated and the value of 18 F-FDG-PET/CT was assessed after treating the xenografts. Results: 10 Gy X-ray irradiation decreased the weight of Hep-2 xenografts 8 and 12 days after treatment, and the weights of Tu212 xenografts 8 days after treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after treatment. There was a synergistic interaction among the three treatments (GLUT-1 AS-ODNs, HIF-1α AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis, decreasing MVD, and increasing necrosis in Hep-2 xenografts 8 days after treatment ( p < 0.05) and in Tu212 xenografts 12 days after treatment ( p < 0.001). Standardized uptake value (tumor/normal tissue)( SUVmaxT/N) did not show a statistically significant correlation with GLUT1 and HIF-1α expression and therapeutic effect (necrosis, apoptosis). Conclusions: Simultaneous inhibition of HIF-1α and GLUT-1 expression might increase the radiosensitivity of laryngeal carcinoma, decreasing MVD, and promoting apoptosis and necrosis. 18 F-FDG-PET/CT wasn’t useful in evaluating the therapeutic effect on laryngeal cancer in this animal study.