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Aim: To explore the correlations between examination tolerance and anxiety, knowledge needs and examination cooperation in sedation‐free gastroscopy examinees. Design: Cross‐sectional survey using convenience sampling. Methods: A total of 170 healthy adults who underwent sedation‐free gastroenteroscopy were asked to complete a visual analogue scale (VAS) to rate their examination tolerance, the state anxiety questionnaire (S‐AI), a newly designed knowledge needs questionnaire and a cooperation questionnaire. Results: The VAS score was 4.47 ± 1.96, the state anxiety score was 39.46 ± 9.81, the total score for knowledge needs was 44.89 ± 11.02, and the average cooperation score was 2.47 ± 0.38. The VAS score during the examination positively correlated with the pretest state anxiety score and pretest knowledge needs score and negatively correlated with the examination cooperation score. The results of multiple linear regression analysis showed that after undergoing the examination for the first time, anxiety, body position and swallowing control were the main factors influencing the examination tolerance of sedation‐free gastroscopy examinees. Patient or Public Contribution: We would like to thank the staff and patients of the participating hospital for their assistance and cooperation in performing the current study. [ABSTRACT FROM AUTHOR]

Objective: Our objective is to assess the oncologic outcomes of observation, elective neck dissection (END), and elective neck irradiation (ENI) in the neck management of head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis (P+) and to evaluate the quality of life (QoL) of patients who received END or ENI. Methods: Patients with P+ HNcSCC were retrospectively enrolled. The impact of observation, END, and ENI on regional control (RC) and overall survival (OS) was analyzed using Cox proportional hazards model with presentation via hazard ratio (HR) with a 95% confidence interval (CI). QoL was evaluated using the University of Washington Quality of Life questionnaire. Results: A total of 134 patients were included in our analysis. In the Cox model for RC, both END and ENI had decreased HRs of 0.27 (95% CI: 0.15–0.69) and 0.34 (95% CI: 0.18–0.86), respectively, in comparison with observation. In the Cox model for OS, both END (p = 0.001, HR: 0.22, 95% CI: 0.10–0.72) and ENI (p = 0.006, HR: 0.30, 95% CI: 0.17–0.83) were superior to observation. In patients with three or more positive parotid lymph nodes, END resulted in significantly better RC (p < 0.001) and OS (p = 0.001) compared with ENI. The two groups were found to be comparable in all 12 domains of the University of Washington Quality of Life questionnaire. Conclusion: In the neck management of P+ HNcSCC, observation is not recommended. END is the preferred option, but ENI is an alternative method without compromise to survival or QoL, except in cases with three or more metastatic parotid lymph nodes. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of the number and ratio of metastatic lymph nodes (LNs) on prognosis in submandibular gland cancer. To this end, patients were selected from the Surveillance, Epidemiology, and End Results database retrospectively. The effect of the number and ratio of metastatic LNs and the American Joint Committee on Cancer (AJCC) N stage on disease-specific survival (DSS) and overall survival (OS) was analyzed. In addition, prognostic models based on LN evaluation methods were developed to predict the OS and DSS. A total of 914 patients were included. Binary recursive partitioning analysis determined the optimal cut-off number of metastatic LNs (0 vs. 1–2. vs. 3+). The presence of 3+ metastatic LNs carried the greatest impact on prognosis, followed by 1–2 positive LNs occurrences. The ratio of metastatic LNs was an independent factor for DSS and OS. The model had a higher likelihood ratio and C-index than those in the Cox model based on the AJCC N stage. Quantitative LN burden and ratio of metastatic LNs provides better survival stratification than the AJCC N stage. [ABSTRACT FROM AUTHOR]

Survival significance of parotid lymph node (LN) factors in parotid cancer remains unclear, our goal was to assess the impact of number, size, and extranodal extension (ENE) of metastatic parotid LNs on prognosis in parotid cancer. Patients with surgically treated parotid cancer were retrospectively enrolled. Primary outcome variable was recurrence-free survival (RFS) and overall survival (OS). The hazard ratios (HRs) of main predictive variables including the number, size, and ENE of positive parotid LNs on RFS and OS were analyzed using Cox model. The secondary outcome variable was ENE of metastatic parotid LN, its association with clinicopathologic variables were evaluated using Chi-square test. In total, 453 patients (186 male and 267 female) were included. The 10-year RFS and OS rates were 73% (95%CI: 69%–77%) and 61% (95%CI: 55%–67%), respectively. In Cox model, compared none parotid LN metastasis, one metastatic parotid LN did not offer additional compromise of RFS (p = 0.224) or OS (p = 0.135), but two or more positive LNs decreased the control of RFS (HR: 2.017; 95%CI: 1.378–4.632) and OS (HR: 2.173; 95%CI: 1.367–4.275). When accounting for the number of metastatic LNs, LN size or ENE was no longer related to RFS or OS. ENE of parotid LN tended to develop if there was presence of T3/4 stage, lymphovascular invasion, high histologic grade, N2/3 stage, and three or more positive parotid LNs. Quantitative parotid LN burden but not ENE or LN size is an important determinant of survival in patients with parotid cancer. [ABSTRACT FROM AUTHOR]

Stimulation of insulin secretion by glucose and other secretagogues from pancreatic islet [beta]-cells is mediated by multiple signaling pathways. Rac1 is a member of Rho family GTPases regulating cytoskeletal organization, and recent evidence also implicates Rac1 in exocytotic processes. Herein, we report that exposure of insulin-secreting (INS) cells to stimulatory glucose concentrations caused translocation of Rac1 from cytosol to the membrane traction (including the plasmalemma), an indication of Rac1 activation. Furthermore, glucose stimulation increased Rac1 GTPase activity. Time course study indicates that such an effect is demonstrable only after 15 min stimulation with glucose. Expression of a dominant-negative Rac1 mutant (N17Racl) abolished glucose-induced translocation of Rac1 and significantly inhibited insulin secretion stimulated by glucose and forskolin. This inhibitory effect on glucose-stimulated insulin secretion was more apparent in the late phase of secretion. However, N17Rac1 expression did not significantly affect insulin secretion induced by high [K.sup.+]. INS-1 cells expressing N17Racl also displayed significant morphological changes and disappearance of F-actin structures. Expression of wild-type Rac1 or a constitutively active Rac1 mutant (V12Racl) did not significantly affect either the stimulated insulin secretion or basal release, suggesting that Rac1 activation is essential, but not sufficient, for evoking secretory process. These data suggest, for the first time, that Rac1 may be involved in glucose- and forskolin-stimulated insulin secretion, possibly at the level of recruitment of secretory granules through actin cytoskeletal network reorganization. G protein; translocation; F-actin cytoskeleton

Objective: The aim of this study is to identify the risk factors associated with orocutaneous fistula (OCF) formation after free flap reconstruction for oral squamous cell carcinoma (SCC). Methods: Patients undergoing free flap reconstruction for oral SCC were retrospectively enrolled. The relationship between clinicopathologic variables and OCF formation was analyzed by univariate and multivariate analyses. Results: A total of 87 OCFs occurred in 856 patients. Univariate analysis revealed cachexia, tumor at the tongue/floor of the mouth (TFOM), T4 stage, preoperative hemoglobin level, pull-through procedure, preoperative albumin level, and surgical site infection were associated with the formation of OCF. Multivariate analysis confirmed the independence of cachexia, TFOM, T4 stage, and surgical site infection in predicting OCF development. Conventional wound care could achieve successful fistula closure in 82.4% of the patients with a median time of 28 days. Conclusions: OCF formation was common after free flap reconstruction. The presence of cachexia, TFOM tumor site, T4 stage, and surgical site infection significantly increased the risk of OCF formation. Although it required a long period, conventional wound care can obtain satisfactory outcomes in OCF management. [ABSTRACT FROM AUTHOR]

To examine the influence of adjuvant chemoradiation therapy (CRT) on survival, stratified by varying numbers and level involved of metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). Patients who underwent surgery for metastatic, negative margin HNSCC without extranodal extension were retrospectively enrolled and divided into two groups based on adjuvant therapy received: radiotherapy (RT) and CRT. The impact of RT versus CRT, stratified by the number of positive lymph nodes and the level involved, on Disease-Free Survival (DFS) and Overall Survival (OS) was analyzed. Following propensity score matching, a total of 580 patients were included. The burden and level of lymph node metastasis were independent predictors of poorer survival. Among patients with no more than two positive lymph nodes or involvement of levels I-III, the addition of chemotherapy to RT did not demonstrate a significant improvement in prognosis. However, in patients with three or more positive lymph nodes, CRT showed improved DFS and OS compared to RT. In patients with involvement of levels IV-V, the addition of chemotherapy to RT resulted in a significant 24 % reduction in the risk of recurrence and a 20 % decrease in the risk of death. Incorporation of adjuvant chemoradiation can lead to a favorable prognosis in patients with metastatic HNSCC. This impact was notable in cases where there were three or more positive lymph nodes or involvement of levels IV-V. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the diagnostic benefit of fine needle aspiration biopsy cytology (FNAB-C) and core needle biopsy tissue (CNB-T) with the addition of thyroglobulin (Tg) in the washout of the needle or BRAF V600E mutation assessment in assessing cervical lymph node metastasis (LNM) in papillary thyroid carcinoma. Materials and Methods: A total of 186 lymph nodes were punctured by fine or core needle. The diagnostic performance of FNAB-C and CNB-T with Tg in the washout or BRAF V600E mutation assessment was compared. Results: The optimal cutoff value of FNAB-Tg was 1.0 ng/ml, with an AUC of 0.976. The sensitivity and specificity of FNAB-C in predicting cervical LNM were 97.4% and 71.4%, respectively, and the addition of FNAB-Tg could contribute to a sensitivity of 100% and a specificity of 95%, but the introduction of BRAF V600E mutation assessment was associated with a decreased sensitivity of 96.3% and a decreased specificity of 50.0%. The FNAB-Tg level showed a comparable distribution in malignant lymph nodes with different TgAb statuses, serum TSH levels, and serum Tg levels. The sensitivity and specificity of CNB-T in predicting cervical LNM were 98.9% and 100%, respectively. The addition of CNB-Tg did not alter the diagnostic ability, but the introduction of BRAF V600E mutation assessment obtained the best performance, with a sensitivity of 100% and specificity of 100%. Conclusion: The sensitivity and specificity of FNAB-C could be increased if combined with FNAB-Tg. CNB-T alone could provide satisfactory diagnostic reliability. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the significance of the number of positive lymph nodes in oral squamous cell carcinoma (SCC) stratified by p16. Methods: A total of 674 patients were retrospectively enrolled and divided into 4 groups based on their number of positive lymph nodes (0 vs. 1–2 vs. 3–4 vs. ≥5). The Kaplan-Meier method was used to calculate the disease-free survival (DFS) and disease-specific survival (DSS) rates. Cox model was used to evaluate the independent risk factor. Results: p16 showed positivity in 85 patients with a rate of 12.6%. In patients with p16 negativity, the 5-year DFS rates were 52%, 39%, and 21% in patients with 0, 1–2, and 3–4 positive lymph nodes, respectively, in patients with ≥5 positive lymph nodes, all patients developed recurrence within 2 years after operation, the difference was significant; the 5-year DSS rates were 60, 38, and 18% in patients with 0, 1–2, and 3–4 positive lymph nodes, respectively, in patients with ≥5 positive lymph nodes, all patients died within 4-years after operation. The difference was significant. In p16 positivity patients, the 3-year DFS rates were 41% and 17% in patients with 0–2 and ≥3 positive lymph nodes, respectively, the difference was significant; the 3-year DSS rates were 84 and 46% in patients with 0–2 and ≥3 positive lymph nodes, the difference was significant. Conclusions: The number of positive lymph nodes is significantly associated with the survival in oral SCC, its survival effect is not affected by p16 status. [ABSTRACT FROM AUTHOR]

Objectives: Our goal was to analyze the possibility of using metabolic tumor volume (MTV) to predict occult cervical metastasis and survival in cT1-2N0 squamous cell carcinoma (SCC) of the tongue. Methods: Data on the primary tumor MTV and cervical node status as determined by the maximum standardized uptake value were retrieved. The sensitivity and specificity in predicting occult metastasis were calculated with a fourfold table. Associations between occult metastasis and clinicopathological variables were evaluated by univariate and multivariate analyses. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS). Results: A total of 24 (20.3%) of 118 patients had occult metastasis. An MTV cutoff value of 4.3 cm3 showed a sensitivity of 50.0% and a specificity of 76.6% in predicting occult metastasis. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT1 tumors were 66.6 and 89.8%, respectively, with values of 83.3 and 67.3%, respectively, when combined with the MTV. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT2 tumors were 72.2 and 82.2%, respectively, with values of 88.9 and 57.8%, respectively, when combined with the MTV. Patients with MTV ≥4.3 cm3 had a higher occult metastasis rate than patients with MTV <4.3 cm3. The 5-year LRC and DSS rates were 86 and 94%, respectively, in patients with MTV <4.3 cm3 and 54 and 72%, respectively, in patients with MTV ≥4.3 cm3. Both differences were found to be significant in univariate and multivariate analyses. Conclusions: MTV ≥4.3 cm3 was associated with an increased probability of occult metastasis and lower LRC and DSS rates in early-stage SCC of the tongue. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To analyze the prognostic value of a family cancer history for predicting survival in patients with oral tongue squamous cell carcinoma (SCC).Study Design: Retrospective case series.Methods: Each patient with a family history was paired with one patient with sporadic oral tongue SCC without a family history. The primary endpoint was disease-specific survival (DSS).Results: In total, 124 patients were enrolled as participants with a family cancer history, and the 5-year DSS rate was 51%. In the matched group, the 5-year DSS rate was 40%. The difference was significant (P = .032). In the smoking patients with a family history, the 5-year DSS rate was 43%. In the smoking patients from the matched group, the 5-year DSS rate was 17%; the difference was significant (P = .028). In nonsmoking patients with a history of cancer, the 5-year DSS rate was 51%; in nonsmoking patients in the matched group, the 5-year DSS rate was 40%; the difference was not significant (P = .141).Conclusions: A family cancer history is associated with improved DSS in surgically treated oral tongue SCC patients.Level Of Evidence: 4 Laryngoscope, 130:E605-E610, 2020. [ABSTRACT FROM AUTHOR]

Objective: To analyze the role of frequency of heterotypic neutrophil-in-tumor structure (FNiT) in the prognosis of patients with buccal mucosa squamous cell carcinoma (BMSCC). Methods: In vitro , we cocultured BMSCC cell line-H157 with neutrophils to form heterotypic neutrophil-in-tumor structures, which were then subject to fluorescence staining. Clinically, 145 patients were retrospectively enrolled. Associations between FNiT and clinicopathological variables including age, sex, smoking history, drinking history, betel nut chewing, tumor stage, node stage, metastasis, disease stage, lymphovascular invasion, extranodal extension, perineural invasion, and tumor grade were analyzed by chi-square test, and the main endpoints of interest were recurrence-free survival (RFS) and disease-specific survival (DSS) which were analyzed by the Kaplan-Meier method and Cox model. Results: Fluorescent staining results of typical heterotypic neutrophil-in-tumor structure showed that well-differentiated H157 cells had a stronger ability to internalize more neutrophils than poorly-differentiated H157 cells, with the latter often internalizing only one neutrophil or nothing. The mean FNiT was 4.2‰, with a range from 2.3‰ to 7.8‰. A total of 80 patients relapsed and 84 patients died of the disease. The 5-year RFS and DSS rate was 42% and 42%, respectively. Patients with an FNiT≥4.2‰ had a significantly higher risk for locoregional recurrence and cancer-caused death than those with an FNiT<4.2‰ (p=0.001 and p<0.001, respectively). The FNiT alone was independently significant in predicting poor RFS, and the FNiT along with tumor grade was an independent predictor for DSS. Conclusion: The FNiT as a novel predictor is significantly negatively associated with both the RFS and DSS of patients with BMSCC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of lingual lymph node (LLN) metastasis on locoregional control (LRC) in patients with locally advanced tongue squamous cell carcinoma (SCC).Methods: A total of 231 patients were prospectively enrolled. Analyses focused on the association between the LLN metastasis and clinical pathologic variables as well as the significance of LLN metastasis in predicting prognosis.Results: LLNs were noted in 58 patients, 33 of whom were positive for LLN metastasis. LLN metastasis was significantly related to adverse pathologic characteristics. In patients with LLN metastasis, the 5-year LRC rate was 45%. In patients without LLN metastasis, the 5-year LRC rate was 65% and the difference was significant (P = 0.013). Further, Cox model analysis confirmed the independence of LLN metastasis from prognosis prediction.Conclusion: LLN metastasis in locally advanced tongue SCC is relatively uncommon; however, LLNs should be routinely dissected because they could significantly decrease locoregional control.Level Of Evidence: 2b. Laryngoscope, 129:2527-2530, 2019. [ABSTRACT FROM AUTHOR]

Abstract: Generating surrogate insulin-producing cells from embryonic stem cells (ESCs) through in vitro replication of successive steps during pancreatic development has been challenging . Here we describe a novel reproducible protocol to establish homogeneous and scalable insulin-producing cell lines from mouse (m) ESCs via differentiation of the previously described lineage-restricted clonal mESC-derived E-RoSH cells. Unlike their parental mESCs, E-RoSH cells expressed high levels of mesodermal and endodermal genes. Nutrient depletion in the presence of nicotinamide inhibited proliferation of E-RoSH cells and induced differentiation into heterogeneous cultures comprising vascular-like structures that produced detectable levels of insulin and C-peptide in an equimolar ratio. Limiting dilution of these cultures resulted in the isolation of eight independent insulin-producing cell lines in five experiments. All these lines were cloned and shown to be amenable to repeated cycles of freeze and thaw and to replicate for months with a doubling time of 3–4 days. Under such conditions, the cultured cells exhibited genomic, structural, biochemical, and pharmacological properties of pancreatic β cells, including storage of an equimolar ratio of insulin and C-peptide in granules and release of the contents of these organelles through a glucose-sensitive machinery. After transplantation, these cells reversed hyperglycemia in streptozotocin-treated SCID mice and did not form teratomas. [Copyright &y& Elsevier]

Abstract: We have previously described the derivation of insulin-producing cell lines from mouse embryonic stem cells (mESCs) by differentiation of an intermediate lineage-restricted E-RoSH cell line through nutrient depletion in the presence of nicotinamide followed by limiting dilution. Here we investigated whether insulin-producing cell lines could be similarly derived directly from mouse embryo cells or tissues. Using a similar approach, we generated the RoSH2.K and MEPI-1 to -14 insulin-producing cell lines from the 5.5-dpc embryo-derived E-RoSH-analogous RoSH2 cell line and a 6.0-dpc mouse embryo culture, respectively. Insulin content was ∼8 μg/106 MEPI-1 cells and 0.5 μg/106 RoSH2.K cells. Like insulin-producing mESC-derived ERoSHK cell lines, both MEPI and RoSH2.K lines were amenable to repeated cycles of freeze and thaw, replicated for months with a doubling time of 3–4 days, and exhibited genomic, structural, biochemical, and pharmacological properties of pancreatic β-cells, including storage and release of insulin and C-peptide in an equimolar ratio. Transplantation of these cells also reversed hyperglycemia in streptozotocin-treated SCID mice and did not induce teratoma. Like ERoSHK cells, both RoSH2.K and MEPI-1 cells also induced hypoglycemia in the mice. Therefore, our protocol is robust and could reproducibly generate insulin-producing cell lines from different embryonic cell sources. [Copyright &y& Elsevier]

Glucose induces insulin secretion from β-cells by a complex signaling network. Our earlier work has shown that the small G-protein Rac1 participates in glucose-stimulated insulin secretion probably via maintaining a functional actin structure for recruitment of insulin granules. This study aimed to define the downstream effectors that may mediate the Rac1 effects, focusing on the type lot phosphatidylinositol-4-phosphate 5-kinase (PIP5K-Iα), a key enzyme to form phosphatidylinositol-4, 5-bisphosphate (PIP[sub 2]). Suppression of Rac1 function inhibited PIP5K-Iα translocation from cytosol to the membranes in β-cells. PIP5K-Iα has been shown to affect actin cytoskeletal dynamics, but its possible role in secretory process is unclear. We used RNA interference technique to knock down PIP5K-Iα in INS-I β-cells. Transfection of siRNA duplexes targeting the kinase resulted in a marked decease of its mRNA level by 75% as assessed by real-time PCR. In addition, glucose stimulation reduced PIP[sub 2] content in the plasma membrane, but such effect was suppressed in PIP5K-Iα knock-downed cells. The latter also displayed disruption of F-actin structure (FITC-phalloidin staining) accompanying dramatically morphological changes observed under confocal microscopy. Their cellular actin content was also significantly decreased by 24% (P<0.05). Insulin secretion from PIP5K-Iα knock-downed cells under various conditions was measured by RIA. Basal insulin release at 2.8 mM glucose was significantly increased by 1.15 fold (P<0.01) in PIP5K-Iα knock-downed cells. However, high (16.7mM) glu cose-stimulated insulin secretion was markedly reduced by ∼40% (P<0.01). Similarly, insulin secretion induced by 16.7mM glucose plus 1 p.M forskolin was also inhibited in these cells. In contrast, PIP5K-Iα knockdown did not attenuate high KC1-induced insulin release. PIP5K-Iα knockdown appeared not to affect cell growth and death, assessed by flow cytometry. Our results suggest that PIP5K-Iα is involved in the regulation of actin cytoskeleton and glucose signaling, playing a role in glucose-induced insulin secretion in β-cells. [ABSTRACT FROM AUTHOR]

Background: To explore the metabolic differences of follicular thyroid carcinoma (FTC) by metabonomics, to find potential biomarkers for the diagnosis of FTC, and to explore the pathogenesis and diagnosis and treatment strategies of FTC., Method: The metabonomics of 15 patients with FTC and 15 patients with follicular thyroid nodules(FTN) treated in Henan Cancer Hospital were analyzed by liquid chromatography-mass spectrometry (LC-MS)., Results: The analysis showed that the metabolite profiles of FTC tissues could be well distinguished from those of control tissues, and 6 kinds of lipids were identified respectively, including lysophosphatidic acid(LysoPA) [LysoPA(0:0/18:0),LysoPA(0:0/18:2(9Z,12Z)],LysoPA[20:4(8Z,11Z,14Z,17Z)/0:0)]; phosphatidic acid(PA) [PA(20:3(8Z,11Z,14Z)/0:0),PA(20:4(5Z,8Z,11Z,14Z)/0:0),PA(20:5(5Z,8Z,11Z,14Z,17Z)/0:0)]; lysophosphatidylcholine(LPC) [LPC(18:1),LPC(16:0),LPC[16:1(9Z)/0:0],LPC(17:0),LPC[22:4(7Z,10Z,13Z,16Z),LPC(20:2(11Z,14Z); phosphatidylcholine(PC)(PC(14:0/0:0),PC(16:0/0:0); sphingomyelin(SM) (d18:0/12:0); fatty acid(FA)(18:1(OH3)]. There are 2 kinds of amino acids, including L-glutamate,L-glutamine.There are 3 other metabolites, including retinol,flavin adenine dinucleotide,androsterone glucuronide.Lipid metabolites are the main metabolites in these metabolites.The metabolic pathways related to FTC were analyzed by KEGG and HMDB, and 9 metabolic pathways were found, including 4 amino acid related metabolic pathways, 1 lipid metabolic pathways and 4 other related pathways., Conclusion: There are significant differences in many metabonomic characteristics between FTC and FTN, suggesting that these metabolites can be used as potential biomarkers. Further study found that LysoPA and its analogues can be used as biomarkers in the early diagnosis of FTC.It may be related to the abnormal metabolism of phospholipase D (PLD), the key enzyme of LysoPA synthesis caused by RAS pathway. At the same time, it was found that the metabolic pathway of amino acids and lipids was the main metabolic pathway of FTC. The abnormality of LysoPA may be the cause of follicular tumor carcinogenesis caused by lipid metabolic pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Yang, Du, Li, Wu, Luo, Liu and Fan.)

Objective: To reveal a novel pathological feature: heterotypic neutrophil-in-tumor structure (hNiT) first discovered in patients with oropharyngeal squamous cell carcinoma (OPSCC), to analyze the prognostic role of hNiT in OPSCC patients and to explore the role of p16 in the formation of hNiT structures., Methods: Clinically, 197 patients were enrolled. Clinicopathological information was extracted and analyzed. All pathologic sections made from primary tumors were re-evaluated by immunohistochemistry and immunostaining. In vitro , we cocultured OPSCC cell line SCC-15 with neutrophils to form hNiT structures, which were then subject to fluorescence staining. By RNAi and overexpression techniques, we investigated the role of CDKN2A in the formation of hNiTs. We validated the two techniques by qPCR and Western Blot., Results: The hNiT as a novel pathological feature was first discovered in the tissues of OPSCC. The FNiT was significantly associated with tumor stage, disease stage, p16 and tumor grade. A total of 119 patients died of the disease, and the 5-year disease-specific survival (DSS) rate was 36%. The median survival time was 52.6 months. In patients with an FNiT<0.5%, the 5-year DSS rate was 40%; in patients with an FNiT>=0.5%, the 5-year DSS was 28%, and the difference was significant (p=0.001). Cox model analysis showed that FNiT along with disease stage, p16 and tumor grade was an independent prognostic factor for DSS. Immunostaining results of p16 expression showed hNiT formation was negatively correlated to p16 in OPSCC as well as in the hNiT formation assays in vitro indicated by fluorescent staining. Function assays of CDKN2A implied that reduce CDKN2A promoted the formation of hNiT while elevated CDKN2A impeded the hNiT formation., Conclusion: The hNiT as a novel pathological feature is associated with the adverse prognosis of OPSCC patients with p16 inhibiting the formation of hNiT structures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fan, Li, Fang, Yang, Zhang, Du, Liu and Luo.)

Purpose: Our goal was to analyze the feasibility of submandibular gland (SMG) preservation in cT1-2N0 floor of the mouth (FOM) squamous cell carcinoma (SCC) patients. Methods: Patients with cT1-2N0 FOM SCC were retrospectively enrolled and divided into two groups according to the management of the SMG. Level 1b tissues were divided into six groups according to their location with respect to the SMG. The Kaplan-Meier method was used to calculate the locoregional control (LRC) and disease-specific survival (DSS) rates. A Cox model was used to determine the independent risk factors. Results: Twenty-nine patients underwent SMG-preserving neck dissection, and lymph node metastasis occurred in the superior group in 3 of the 37 dissections with a prevalence of 8.1% and in the anterior group in 2 of the 37 dissections with a prevalence of 5.4%. In patients without SMG preservation, lymph node metastasis occurred in the superior group in 7 of the 137 dissections with a prevalence of 5.1% and in the anterior group in 6 of the 137 dissections with a prevalence of 4.4%. The only pattern of SMG involvement was invasion by positive lymph nodes. The 5-year LRC rates for patients with SMG preservation and patients with SMG excision were 84 and 73%, respectively, and the difference was not significant ( p = 0.239). The 5-year DSS rates for patients with SMG preservation and patients with SMG excision were 88 and 84%, respectively, and the difference was not significant ( p = 0.524). Conclusions: In early-stage FOM SCC patients, SMG involvement is rare, the most common metastatic site in level 1b is the superior group, and SMG preservation does not decrease the LRC or DSS rates. Therefore, the findings suggest that there might be high feasibility of SMG-preserving neck dissection in cT1-2N0 FOM SCC., (Copyright © 2020 Du, Fang, Liu, Chen, Luo and Zhang.)

BACKGROUND lncRNA-ATB plays an oncogenic role in various types of malignancies, but its involvement in papillary thyroid carcinoma (PTC) cells, which is a main type of thyroid cancer, is unknown. MATERIAL AND METHODS A total of 76 patients with PTC and 28 people with normal physiological conditions were included in this study. Tumor tissues and adjacent healthy tissues were collected from PTC patients and blood was extracted from both patients and healthy controls. Expression of lncRNA-ATB in those tissues was detected by qRT-PCR. All patients were followed up for 5 years and diagnostic and prognostic values of serum lncRNA-ATB for PTC were investigated by ROC curve analysis and survival curve analysis, respectively. lncRNA-ATB overexpression PTC cell lines were established and effects of lncRNA-ATB overexpression on cell migration and invasion were investigated by Transwell cell migration and invasion assay, respectively. Effects of lncRNA-ATB overexpression on TGF-β1 expression were investigated by Western blot. RESULTS lncRNA-ATB expression level was higher in tumor tissues than in adjacent healthy tissues in most PTC patients. Serum level of lncRNA-ATB was higher in cancer patients than in healthy control. Serum lncRNA-ATB can be used to accurately predict PTC and its prognosis. lncRNA-ATB overexpression promoted tumor cell migration and invasion, lncRNA-ATB overexpression showed no significant effects on TGF-β1 expression, and TGF-β1 treatment increased the expression level of lncRNA-ATB. CONCLUSIONS Upregulation of lncRNA-ATB by TGF-b1 promotes migration and invasion of PTC cells.

Insulin secretion from beta-cells is regulated by a complex signaling network. Our earlier study has reported that Rac1 participates in glucose- and cAMP-induced insulin secretion probably via maintaining a functional actin structure for recruitment of insulin granules. Type Ialpha phosphatidylinositol-4-phosphate 5-kinase (PIP5K-Ialpha) is a downstream effector of Rac1 and a critical enzyme for synthesis of phosphatidylinositol-4,5-bisphosphate (PIP(2)). By using an RNA interference technique, PIP5K-Ialpha in INS-1 beta-cells could be specifically knocked down by 70-75%. PIP5K-Ialpha knockdown disrupted filamentous actin structure and caused changes in cell morphology. In addition, PIP(2) content in the plasma membrane was reduced and the glucose effect on PIP(2) was abolished but without affecting glucose-induced formation of inositol 1,4,5-trisphosphate. At basal conditions (2.8 mM glucose), PIP5K-Ialpha knockdown doubled insulin secretion, elevated glucose metabolic rate, depolarized resting membrane potential, and raised cytoplasmic free Ca(2+) levels ([Ca(2+)](i)). The total insulin release at high glucose was increased upon PIP5K-Ialpha knockdown. However, the percent increment of insulin secretion by high glucose and forskolin over the basal release was significantly reduced, an effect more apparent on the late phase of insulin secretion. Metabolism and [Ca(2+)](i) rises at high glucose were also attenuated in cells after PIP5K-Ialpha knockdown. In contrast, PIP5K-Ialpha knockdown had no effect on cell growth and viability. Taken together, our data suggest that PIP5K-Ialpha may play an important role in both the proximal and distal steps of signaling cascade for insulin secretion in beta-cells.

Syncollin was first demonstrated to be a protein capable of affecting granule fusion in a cell-free system, but later studies revealed its luminal localization in zymogen granules. To determine its possible role in exocytosis in the intact cell, syncollin and a truncated form of the protein (lacking the N-terminal hydrophobic domain) were stably transfected in insulin-secreting INS-1 cells since these well-studied exocytotic cells appear not to express the protein per se. Studies by subcellular fractionation analysis, double immunofluorescence staining, and electron microscopy examination revealed that transfection of syncollin produced strong signals in the insulin secretory granules, whereas the product from transfecting the truncated syncollin was predominantly associated with the Golgi apparatus and to a lesser degree with the endoplasmic reticulum. The expressed products were associated with membranes and not the soluble fractions in either cytoplasm or the lumens of organelles. Importantly, insulin release stimulated by various secretagogues was severely impaired in cells expressing syncollin, but not affected by expressing truncated syncollin. Transfection of syncollin appeared not to impede insulin biosynthesis and processing, since cellular contents of proinsulin and insulin and the number of secretory granules were not altered. In addition, the early signals (membrane depolarization and Ca(2+) responses) for regulated insulin secretion were unaffected. These findings indicate that syncollin may be targeted to insulin secretory granules specifically and impair regulated secretion at a distal stage.