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BACKGROUND: The symptom burden was tremendous and rates of psychological distress were high because of laryngectomy in Laryngeal carcinoma. Anxiety and depression as mainly psychological distress influenced their sleep, pain, and the quality of life (QOL). This study aimed to assess the effiacy of computer-assisted Cognitive Behavioral Therapy (cCBT) for psychological outcomes and QOL in patients with laryngectomy, in addition to overall experience with health care service, during the perioperative period. METHODS: A cCBT program was be customized focused on improving anxiety and depressive symptoms among patients with laryngectomy, and then its effectiveness was assessed. Participants were randomly assigned to the TAU (treatment as usual) group (n=40) or CCBT group (cCBT+ TAU, n = 40). The primary outcome measures were the State Anxiety Inventory (SAI), Patients Health Questionnaire-9 (PHQ-9). The secondary outcome measures were the Athens Insomnia Scale (AIS), Visual Analogue Scale-10 (VAS-10). The outcomes were obtained from patients before intervention (T1), 1 hour before surgery (T2), postoperative 3-day (T3), postoperative 7-day (T4), and postoperative 10-day(T5: after intervention completed). Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) and satisfaction for health care service were assessed before discharge. RESULTS: A mixed linear model displayed significant improvement in symptoms of anxiety, depression, insomnia, and pain in the two groups (all p<0.001); and revealed a significant decreasing on the SAI, PHQ-9, AIS, and VAS-10 scores in the CCBT group compared to that of TAU group during the post-intervention periods (all p<0.05). Furthermore, the other QOL of patients were higher except for physical well-being (p=0.176) and the satisfaction scores were higher in the CCBT group than that of TAU group (all p<0.05). CONCLUSION: The new developed cCBT program has a positive effect on psychosomatic symptoms surgery-related among patients with laryngectomy,. And patients with cCBT program reported high levels of QOL and satisfaction during perioperative period. To minimize face-to-face contact, the computer-assisted intervention may be an attractive approach.

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BACKGROUND: The core nursing outcomes for laryngeal carcinoma in China needed further screening and revision. This study aimed to evaluate and revise a questionnaire according to the "Core Nursing Outcomes for Otorhinolaryngology Head-Neck" of the Nursing Outcomes Classification (NOC, 5th Edition), and determine suitable postoperative nursing outcomes for patients with laryngeal carcinoma in China. METHODS: The commonly used postoperative nursing outcomes for laryngeal carcinoma were screened using a questionnaire given to 93 nurses. An initial expert consultation questionnaire was constructed to discuss the indicators for each nursing outcome. A total of 20 experts were identified using the Delphi method, and their recommendations and revisions on the selected nursing outcomes were collected. RESULTS: A total of 14 postoperative core nursing outcomes and 69 indicators were identified for postoperative patients with laryngeal carcinoma, which are subordinate to 4 domains of the NOC: "Physiologic Health", "Psychosocial Health", "Health Knowledge & Behavior", and "Perceived Health". CONCLUSIONS: The screening and revision of the NOC outcomes and indicators of the Delphi method could be applied to assess the effect of nursing intervention and the quality of the nursing service in China.

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Objective:To investigate the expression of LINC00520 in laryngeal squamous cell carcinoma(LSCC),and analyze its relevance and roles in carcinogenesis and development of LSCC.Method:The expression of LINC00520 in laryngeal squamous cell carcinoma tissue and paired adjacent normal tissue was determined by real-time PCR.The relationship between the expression of LINC00520 and the clinicopathological characteristics including clinical stage,pathological type,histological grade and lymph node metastasis of LSCC was analyzed.Result:(1)The LINC00520 expression level was significantly upregulated in LSCC tissues compared to that of paired adjacent normal tissues(P<0.000 1).(2)There were no statistical differences of the LINC00520 expression level among supraglottic,glottic and subglottic LSCCs(P>0.05).The LINC00520 expression level had no significant changes in poorly differentiated LSCC compared with that of well and moderately differentiated counterparts(P>0.05).Moreover,the expression of LINC00520 had no significant difference between T1+T2 stage and T3+T4 stage LSCC tissues(P>0.05).Interestingly,the LINC00520 level in LSCC with lymph node metastasis was significantly higher than that in patients without lymph node metastasis(P<0.01).Conclusion:Upregulation of LINC00520 in LSCC may contribute to its metastasis.

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BACKGROUND: Melanin and manganese are both indispensable natural substances that play crucial roles in the human body. Melanin has been used as a multimodality imaging nanoplatform for biology science research because of its natural binding ability with metal ions (eg, 64Cu2+, Fe3+, and Gd3+). Because of its effects on T1 signal enhancement, Mn-based nanoparticles have been used in magnetic resonance (MR) quantitative cell tracking in vivo. Stem cell tracking in vivo is an essential technology used to characterize engrafted stem cells, including cellular viability, biodistribution, differentiation capacity, and long-term fate. METHODS: In the present study, manganese(II) ions chelated to melanin nanoparticles [MNP-Mn(II)] were synthesized. The characteristics, stem cell labeling efficiency, and cytotoxicity of the nanoparticles were evaluated. MR imaging of the labeled stem cells in vivo and in vitro were also further performed. In T1 relaxivity (r1), MNP-Mn(II) were significantly more abundant than Omniscan. Bone marrow-derived stem cells (BMSCs) can be labeled easily by coincubating with MNP-Mn(II), suggesting that MNP-Mn(II) had high biocompatibility. RESULTS: Cell Counting Kit-8 assays revealed that MNP-Mn(II) had almost no cytotoxicity when used to label BMSCs, even with a very high concentration (1,600 µg/mL). BMSCs labeled with MNP-Mn(II) could generate a hyperintense T1 signal both in vitro and in vivo, and the hyperintense T1 signal in vivo persisted for at least 28 days. CONCLUSION: Taken together, our results showed that MNP-Mn(II) possessed many excellent properties for potential quantitative stem cell tracking in vivo.

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A definitive diagnosis of mild traumatic brain injury (mTBI) is difficult due to the absence of biomarkers in standard clinical imaging. The brain is a complex network of interconnected neurons and subtle changes can modulate key networks of cognitive function. The resting state default mode network (DMN) has been shown to be sensitive to changes induced by pathology. This study seeks to determine whether quantitative measures of the DMN are sensitive in distinguishing mTBI subjects. Resting state functional magnetic resonance imaging data were obtained for healthy (n=12) and mTBI subjects (n=15). DMN maps were computed using dual-regression Independent Component Analysis (ICA). A goodness-of-fit (GOF) index was calculated to assess the degree of spatial specificity and sensitivity between healthy controls and mTBI subjects. DMN regions and neuropsychological assessments were examined to identify potential relationships. The resting state DMN maps indicate an increase in spatial coactivity in mTBI subjects within key regions of the DMN. Significant coactivity within the cerebellum and supplementary motor areas of mTBI subjects were also observed. This has not been previously reported in seed-based resting state network analysis. The GOF suggested the presence of high variability within the mTBI subject group, with poor sensitivity and specificity. The neuropsychological data showed correlations between areas of coactivity within the resting state network in the brain with a number of measures of emotion and cognitive functioning. The poor performance of the GOF highlights the key challenge associated with mTBI injury: the high variability in injury mechanisms and subsequent recovery. However, the quantification of the DMN using dual-regression ICA has potential to distinguish mTBI from healthy subjects, and provide information on the relationship of aspects of cognitive and emotional functioning with their potential neural correlates.

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OBJECTIVE: The purposes of this study were to determine whether autophagy was involved in cisplatin (CDDP) resistance and to investigate the role of the autophagy in the regulation of chemosensitivity to CDDP in laryngeal cancer Hep-2 cells. METHODS: A WST-1 assay was performed to determine cell viability and cell proliferation. Autophagy activation and proapoptotic effects were characterized using monodansylcadaverine labeling and Hoechest staining, respectively. Western blot analysis was used to detect the expression of apoptotic and autophagy-related genes. Flow cytometry was used to assess cell apoptosis ratio. RESULTS: Exposure to CDDP induced the aggregation of autophagosomes in the cytoplasms of Hep-2 cells and up-regulated the expression of Beclin 1 and LC3II. However, CDDP treatment could not lead to obvious inhibition of cell proliferation, which implies that the autophagy may protect CDDP-treated cells from undergoing cell death. Meanwhile, the WST-1 assay indicated that knockdown of the autophagic gene Beclin 1 sensitized Hep-2 cells to CDDP. Furthermore, CDDP-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitor 3-methyladenine or small interfering RNA against Beclin 1. For the definite mechanism of Beclin 1-enhancing chemosensitivity to CDDP, we found that Beclin1 augmented CDDP-induced apoptotic signaling via enhancing caspase-9 and caspase-3 activity but not caspase-8. CONCLUSION: Our results suggest that functional autophagy in response to CDDP may lead to cell survival in Hep-2 cells, whereas defective autophagy may contribute to CDDP-induced apoptosis in Hep-2 cells. Thus, modulators of autophagy may be used beneficially as adjunctive therapeutic agents during the treatment of laryngeal cancer with CDDP therapy.

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OBJECTIVE: To study the expressions of key assemblies of cytoskeleton, Fascin-1, Ezrin and Paxillin, in laryngeal squamous cell carcinoma (LSCC) and their correlation with clinicopathologic characteristics, cancer recurrence and survival of patients with LSCC. METHODS: The expressions of Fascin-1, Ezrin and Paxillin proteins were detected by immunohistochemistry in 199 cases of LSCC. Unconditional Logistic regression model or Cox proportional hazards model was used for the analyses of recurrent risks and prognostic factors. RESULTS: Significantly increased expression of Fascin-1, Ezrin or Paxillin expression was showed in the LSCC with poorly differentiated, positively cervical lymph nodal metastasis, and clinical stage III + IV respectively (P < 0.05). The expressions of three kinds of proteins in the recurrent cases were higher than those in non-recurrent cases respectively (χ(2) were 42.479, 43.673 and 22.261, P < 0.05). The highest recurrence rate (69.1%) was observed in group of cases with the highly co-expression of the three kinds of proteins (P < 0.05). The expression of Fascin-1 (OR = 7.89, 95%CI 2.26 - 27.53, P = 0.001), or Ezrin (OR = 2.51, 95%CI 1.18 - 5.32, P < 0.001) was independent risk for recurrence. Five-year disease-free survival rates of patients with high expression of Fascin-1, Ezrin or Paxillin were lower than those of patients with negative or low expressions for the proteins (P < 0.05). Patients with highly co-expression of three kinds of proteins showed the poorest survival prognosis, with a 5-year disease free survival (DFS) of only 26.4% (P < 0.05), and expressions of three proteins were independent prognostic factors for 5-year DFS (P < 0.05). CONCLUSION: Fascin-1, Ezrin, and Paxillin were correlative with LSCC progression and might be potential predictors for cancer recurrence and survival of patients with LSCC, as well as therapeutic targets for LSCC.

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BACKGROUND AND AIMS: Tumor-specific T regulatory cells (Treg) play a critical role in tumor cell survival. The development of tumor-specific Treg is not fully understood. This study aims to elucidate the role of matrix metalloproteinase (MMP)9 in tumor tolerance development. METHODS: We recruited 38 patients with laryngeal cancer (LC) in this study. MMP9 levels in the LC were measured by western blotting. Immune cells were isolated from LC tissue for indicated experiments. The cells' activities were characterized by flow cytometry. RESULTS: High levels of MMP9 were detected in LC that plays a critical role in the development of tolerogenic dendritic cells and LC-specific Tregs. The isolated LC Tregs have the ability to suppress tumor-specific CD8 T cells in a tumor antigen-specific manner. CONCLUSIONS: This study reveals a novel mechanism in tumor tolerance in which MMP9 plays a critical role in tumor survival. The data imply that MMP9 may be a potential target in the treatment of malignant tumors.

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OBJECTIVE: To determine the optimal surgical modality for T3 glottic carcinoma. METHODS: Clinical data of 57 cases of T3 glottic carcinoma were retrospectively reviewed. Their clinical characteristics, surgical procedures and prognosis were analyzed. At different ages and by surgical procedures performed, the 3-year disease-free survival rate of the patients were analyzed. RESULTS: All cases underwent surgical procedures including total laryngectomy, near total laryngectomy and partial laryngectomy, and the 3-year disease-free survival rate was 63.2% (36/57). The 3-year disease-free survival rate of patients who received total laryngectomy was 66.7% (16/24), near total laryngectomy 50.0% (4/8), and partial laryngectomy 64.0% (16/25, P = 0.694). The 3-year survival rate of the cases ≥ 70.0 years old was 70.0% (7/10), and that of < 70 years old was 61.7% (29/47, P = 0.621). Thirty-six cases had neck dissection, including 2 cases with radical neck dissection, 6 cases with modified neck dissection, and 28 cases with selective neck dissection. The lymph node metastasis rate of all cases was 17.5%. Ten cases were diagnosed as postoperative local recurrence, including 1 cases treated with total laryngectomy, 2 cases treated with near total laryngectomy and 7 cases treated with partial laryngectomy. CONCLUSIONS: Both total laryngectomy and partial laryngectomy are important surgical procedures for treating patients with T3 glottic carcinoma. The optimal individual surgical procedure for the patient with T3 glottic carcinoma should be determined on the basis of the local lesions and physical status. Total laryngectomy is prior to partial laryngectomy for the patients with T3 glottic carcinoma ≥ 70 years old.

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OBJECTIVE: To investigate the clinical value of sentinel lymph node (SLN) detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck (cN0) by lymphoscintigraphy method and blue dye. METHODS: Forty patients with cN0 laryngeal neoplasms and ten patients with cN0 hypopharyngeal carcinoma scheduled for tumor resection and neck dissection, were eligible for the study. single photon emission computed tomography (SPECT)/CT lymphoscintigraphy was performed with injection of radioactivity isotope 99Tc(m) labeled sulfur colloid (99Tc(m)-SC). Methylthioninium was injected into the same points as 99Tc(m)-SC during surgery, and the patients underwent lymphatic mapping with a handheld gamma-detecting probe. All removed lymph nodes were examined by routine histopathology. RESULTS: Thirty-five patients with laryngeal carcinoma and six patients with hypopharyngeal carcinoma detected SLN by radiolabeled tracer method, the detection rate of SLN was 82.0%. Twenty-nine patients with laryngeal carcinoma and 4 patients with hypopharyngeal carcinoma detected SLN by blue dye method, the detection rate of SLN was 66.0%. There were significant difference between two groups (chi² = 2.769, P < 0.05), and the number of SLN were respectively 96 and 83 by radiolabeled tracer method and blue dye (chi² = -2.098, P < 0.05), The sensitivity of SLN detection were respectively 83.3% and 66.7%. Twelve (24.0%) patients had lymph node metastasis. CONCLUSIONS: Either lymphoscintigraphy or blue dye mapping can be used to detect the SLN in cN0 laryngeal and hypopharyngeal carcinoma. The lymphoscintigraphy not only preoperatively can locate the accuracy of SLN detection, but also has higher detection rate and sensitivity than dye method.

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Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165-PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38-IRES2-EGFP plasmid. ELISA was used to confirm the expression of VEGF165-PE38 in the transfected cells. These cells released 1396 + or - 131.9 pg VEGF165-PE38/1x10(4) cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary-like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38-IRES2-EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. Quantitative analysis of microvessel density in the treated group was 1.99 + or - 0.69/0.74 mm(2), and was significantly lower than that in the control groups (9.33 + or - 1.99/0.74 mm(2), 8.09 + or - 1.39/0.74 mm(2) and 8.49 + or - 1.69/0.74 mm(2)). Immunohistochemistry analysis indicated that immunotoxin VEGF165-PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165-PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.

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OBJECTIVE: The purpose of this study was to investigate the clinical value of radiolabeled tracer method, methylene blue method and combination of these two methods in detection of sentinel lymph node (SLN), and to evaluate the accuracy of SLN in predicting the cervical lymph nodes status in laryngeal carcinoma patients with clinically negative neck lymph nodes (cN0 ). METHODS: Forty-one patients with cN0 laryngeal neoplasms underwent SLN detection using both of radiolabeled tracer and methylene blue. SLN imaging was performed with laryngoscope-guided injection of radioactive isotope 99Tc(m)-sulfur colloid (SC) into the laryngeal carcinoma before surgery, then all these patients underwent intraoperative lymphatic mapping with a handheld gamma-detecting probe. After mapping of SLN, methylene blue was subsequently injected at the same spots around the tumor in order to identify SLN during surgery. The results of SLN detection by isotope tracer, dye and combination of both methods were compared. RESULTS: The SLN detection rates by radiolabeled tracer, methylene blue and combined method were 87.8%, 70.7% and 92.7%, respectively (P < 0.01). The number of detected SLN was significantly different between radiolabeled tracer method and combined method (P < 0.05), and also between blue dye method and combined method (P < 0.01). However, no statistically significant difference was found between methylene blue method and radiolabeled tracer method (P > 0.05). Nine patients were found to have lymph node metastasis by final pathological examination. The sensitivity, accuracy and negative predictive values of SLN detection by the combined method using radiolabeled tracer and methylene blue were 88.9%, 97.4% and 96.7%, respectively. CONCLUSION: The combined method using radiolabeled tracer and methylene blue can improve the accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately predict the cervical lymph node status in cN0 laryngeal carcinoma.

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T regulatory cells (Treg) have the capability to suppress the skewed immune response, but the generation of antigen (Ag)-specific Treg for therapeutic purpose is a challenge; the mechanism of Ag-specific Treg activation remains obscure. Here, we report that glucuronoxylomannan (GXM) is capable of promoting the development of human tolerogenic dendritic cells (DC). GXM-pulsed DCs increased the expression of forkhead box P3 (Foxp3) in naïve human CD4(+)CD25(-) T cells via activating Fc gamma receptor IIb and activator protein-1 and promoting the expression of transforming growth factor beta in dendritic cells. Furthermore, the conjugated complex of house dust mite Ag, Dermatophagoides pteronyssinus (Der p) 1, and GXM-pulsed DCs to drive the naïve human CD4(+)CD25(-) T cells to develop into the Der p 1-specific Tregs, which efficiently suppressed the Ag-specific Th2 responses. We conclude that GXM-conjugated specific Ag have the capacity to up-regulate the tolerogenic property of DCs and promote the generation of Ag-specific Tregs; the latter can be activated upon the re-exposure to specific Ag and suppress the skewed Ag-specific T helper (Th)2 responses.

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Aberrant T helper (Th)2 polarization plays a critical role in the pathogenesis of allergic disorders; the etiology remains unclear. Dendritic cells (DCs) express T cell immunoglobulin mucin domain (TIM)4 that ligates TIM1 on CD4 T cells to drive them to become Th2 cells, but the pathogenic source of TIM4 is unknown. Here we report that a significant increase in TIM4 expression in human DCs was observed in response to Staphylococcal enterotoxin B (SEB) stimulation via Toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)1 pathway. Coculture SEB-conditioned DCs with naïve CD4 T cells induced Th2 responses that could be abolished using TLR2 or NOD1 or TIM4 or TIM1 with counterpart antibodies or RNA interference. The results demonstrate that Staphylococcus aureus derived SEB promotes the TIM4 production in human DCs. The interaction between TIM4 and TIM1 drives naïve CD4 T cells to develop to Th2 cells.

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The mechanism of food allergy remains unclear. The absorption of intact protein Ag into the intestinal tissue is a prerequisite in the development of intestinal sensitization. Previous studies indicate that thermal stress compromises the intestinal barrier function. Mice were concurrently exposed to thermal stress and oral Ag. Intestinal sensitivity, levels of serum-specific IgE, IL-4 and INF-gamma were assessed. Intestinal dendritic cell, Th1 and Th2 functions were determined. The mice that were treated with thermal stress and oral Ag showed high levels of serum Ag-specific IgE, intestinal mast cell activation in response to oral Ag challenge, suppression of IL-12 expression in the intestinal dendritic cells, inhibition of T-bet expression and Th1 function and marked increases in (GATA)3 expression and Th2 function. Mice exposed to thermal stress alone or oral Ag alone did not show any signs of the intestinal sensitization. Pretreatment with IL-12 inhibited the intestinal sensitization induced by the concurrent exposure to thermal stress and Ag gavage. We conclude that although Ag absorption is essential, Ag absorption alone is insufficient; other accessory factors that can disturb the local immune homeostasis are also required for the induction of intestinal sensitization. The present study illustrates that concurrent exposure to thermal stress and oral Ag can prove to be a factor in the induction of intestinal sensitization by a mechanism of regulating IL-12 expression.

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BACKGROUND: Staphylococcal enterotoxin B (SEB) is a potent immunomodulator and implicated with pathogenesis of inflammatory diseases mediated by Th1 or Th2 dominant immune responses. The objective of this study is to determine a possible association between rhinosinusitis derived SEB and pathogenesis of food allergy (FA). METHODS: The study included chronic rhinosinusitis (CRS) patients with FA (N = 46) or without FA (N = 33). Controls included FA patients without CRS (N = 26) and healthy volunteers (N = 25). In CRS patients, we assessed the parameters associated with FA including prick skin test (PST) reactivity to food allergens, serum levels of allergen-specific IgE and cytokines (IL-4, IL-13, IFN-I3), and the number/reactivity of food-allergen specific Th1/Th2 cells in the peripheral blood before and 2 months after sinus surgery. Changes of these parameters were evaluated in comparison with changes in SEB concentration in the sinus lavage and stool samples and also in vitro reactivity to SEB. In CRS patients with FA, we also assessed changes in reactivity to oral challenge of offending food before and after sinus surgery. RESULTS: Two months following sinus surgery, we observed statistically significant reduction in PST and oral challenge reactivity in CRS patients with FA in parallel to decrease in serum levels of Th2 cytokines (IL-4 and IL-13) and allergen specific IgE. Improvement of reactivity to food allergens was positively associated with decline in SEB concentrations in the sinus lavage and stool samples. In vitro study results also indicated a role of SEB in aggravation of Th2 skewed responses to food allergens. Such changes were not observed in CRS-non FA patients or control FA patients. CONCLUSION: The rhinosinusitis derived SEB plays a certain role in the pathogenesis of FA by augmenting and/or maintaining polarized Th2 responses. Removal of SEB-producing pathogens from the rhinosinuses may be beneficial for attenuating the FA symptoms in patients with CRS-FA.

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