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Objective Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed. Materials and methods The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells. Results OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P P P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor. Conclusions The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC.

Sarcopenia is a core contributor to several health consequences, including falls, fractures, physical limitations and disability. The pathophysiological processes of sarcopenia may be counteracted with the proper diet, delaying sarcopenia onset. Dietary pattern analysis is a whole diet approach used to investigate the relationship between diet and sarcopenia. Here, we aimed to investigate this relationship in an elderly Chinese population. A cross-sectional study with 2423 participants aged more than 60 years was performed. Sarcopenia was defined based on the guidelines of the Asian Working Group for Sarcopenia, composed of low muscle mass plus low grip strength and/or low gait speed. Dietary data were collected using a FFQ that included questions on 100 food items along with their specified serving sizes. Three dietary patterns were derived by factor analysis: sweet pattern, vegetable pattern and animal food pattern. The prevalence of sarcopenia was 16·1 %. The higher vegetable pattern score and animal food pattern score were related to lower prevalence of sarcopenia (Ptrend = 0·006 and < 0·001, respectively); the multivariate-adjusted OR of the prevalence of sarcopenia in the highest v. lowest quartiles were 0·54 (95 % CI 0·34, 0·86) and 0·50 (95 % CI 0·33, 0·74), separately. The sweet pattern score was not significantly related to the prevalence of sarcopenia. The present study showed that vegetable pattern and animal food pattern were related to a lower prevalence of sarcopenia in Chinese older adults. Further studies are required to clarify these findings.

Introduction: Mounting evidence has demonstrated that skeletal muscle and visceral adiposity play crucial roles in glucose metabolism. The purpose of this study was to investigate whether the appendicular skeletal muscle mass index (ASMI) to trunk fat mass (TFM) ratio (ASMI/TFM) is a more specific and identifiable factor for type 2 diabetes mellitus (T2DM) in older adults than conventional anthropometric measures. Methods: This cross-sectional study included 1,370 older adults from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) cohort. ASMI and TFM were measured by using a bioelectrical impedance analyzer, and T2DM was defined with the criteria of the American Diabetes Association. Odds ratios (ORs) were evaluated using multivariable logistic analysis. Results: The prevalence of T2DM is 20.0% in this study. The multivariable-adjusted ORs (95% confidence interval) of T2DM for increasing categories of ASMI/TFM, BMI, and waist circumference (WC) were 1.00 (reference), 0.70 (0.49, 1.02), 0.61 (0.42, 0.89), and 0.45 (0.30, 0.67; p for trend p for trend = 0.10); and 1.00 (reference) and 1.78 (1.19, 2.74; p < 0.01), respectively. Conclusions: Higher ASMI/TFM was associated with a lower prevalence of T2DM in this study of older adults. The T2DM predictive value of ASMI/TFM may be stronger than BMI and WC in this population.

Hypertension is one of the most common chronic cardiovascular diseases in older adults. Frailty and hypertension often coexist in older people, but few studies have explored frailty in older hypertensive adults. We aimed to explore the association of frailty with quality of life in older hypertensive adults. We collected the data of 291 patients with hypertension aged ≥ 60 years. Blood pressure was measured with a standard aneroid sphygmomanometer and an ambulatory blood pressure monitor. The characteristics of the Fried phenotype were used to assess physical frailty. The Medical Outcomes Study’s 36-Item Short Form Health Survey (SF-36) was used to assess the quality of life. Forty-eight (16.5%) patients were frail. Compared with pre-frail or robust older hypertensive patients, those who were frail were older, had higher incidences of living alone, a longer duration of hypertension, lower grip strength, and slower walking speed. Moreover, frail patients had a lower diastolic blood pressure (DBP) and mean arterial pressure (MAP), more chronic diseases, a lower proportion of beta-blocker usage, and worse quality of life. Frailty was positively correlated with pulse pressure and negatively correlated with DBP and MAP, but these associations disappeared after adjustment by age. The SF-36 score was negatively correlated with frailty and positively correlated with grip strength and walking speed. After adjusting for age, the SF-36 total score remained negatively correlated with frailty and positively correlated with walking speed. Frailty states remained significantly associated with the SF-36 score. Frailty was associated with a worse quality of life in older adults with hypertension. Frailty prevention and intervention may help improve the quality of life of older adults with hypertension.

Purpose Treatment recommendations have been widely reported for primary tongue squamous cell carcinoma (TSCC) with contralateral neck metastases (CNMs), but little is known concerning recurrent TSCCs with CNMs, especially in patients who have undergone ipsilateral neck dissection. The aim of this study was to estimate overall survival (OS) and to identify prognostic factors associated with OS in patients treated for recurrent TSCCs. Patients and Methods We performed a retrospective cohort study of patients who underwent salvage surgery (SS) for recurrent TSCC in our institution between January 2010 and December 2014. Before SS, all patients had been surgically treated for primary TSCC with ipsilateral neck dissection. The primary outcome variable was OS, and the patients were grouped by the primary predictor variable of CNM status for comparison. Other heterogeneous variables of interest included demographics, medical histories, clinicopathologic characteristics, surgical data, and adjuvant treatment modalities. In addition, the midline involvement and anatomic subsites of local recurrences were evaluated. Univariate log-rank and Cox regression tests were used for statistical analyses. Results The study sample included 177 subjects with a mean age of 55.4 years, and 44.6% were males. The median OS was 18 months. Within the entire cohort, the incidence of CNM was 23.7% (n = 42), with an inclination (n = 30) for contralateral level I or II. Factors associated with improved survival included CNM (hazard ratio [HR], 2.108; 95% confidence interval [95% CI], 1.341 to 3.315; P = .001), disease-free interval (HR, 0.601; 95% CI, 0.387 to 0.934; P = .023), and local recurrence subsite score (HR, 3.276; 95% CI, 0.924 to 11.623; P = .001). Conclusions Patients with both recurrent TSCCs and CNMs had a dismal prognosis (OS rate, 16.2%) compared with those without CNMs (OS rate, 52.7%). SS for TSCC patients with collateral failures should be used cautiously because of the very unfavorable outcomes.

BACKGROUND Patients with chronic hepatitis B (CHB) with long-term nucleos(t)ide therapy may experience renal insufficiency. Traditional renal function indicators, such as urine protein, serum urea nitrogen (BUN), and serum creatinine, are normal when early mild lesions occur. Therefore, more sensitive renal function indicators are needed. AIM To investigate the significance of early renal injury indicators in evaluating renal injury in patients with CHB with long-term nucleos(t)ide therapy. METHODS We collected the clinical data of 69 outpatients with CHB at Peking University First Hospital from March 2018 to January 2020 who had been treated with long-term nucleos(t)ide therapy and analyzed the results of early renal injury indicators. Continuous normal distribution data were analyzed by the t-test to determine the difference between two groups. Continuous non-normally distributed data were analyzed by the Mann-Whitney U-test between two groups. The Kruskal-Wallis H test was used to determine the differences among multiple groups. Enumeration data were analyzed by the chi-square test. The related factors of early renal injury indicators were analyzed by logistic regression analysis. RESULTS The average treatment duration with nucleos(t)ide analogs of the 69 patients with CHB was 99.7 ± 28.7 mo. The cases of patients with elevated BUN and hypophosphatemia were 6 (8.7%) and 13 (18.8%), respectively; 31 (44.9%) patients had abnormal early renal injury indicators, including 9 patients with abnormal urine microalbumin, 7 patients with abnormal urine immunoglobulin, 6 patients with abnormal urine transferrin, and 19 patients with abnormal α1 microglobulin. There were no significant differences in the mean values of age, sex, BUN, estimated glomerular filtration rate (eGFR), serum uric acid, serum calcium, or serum phosphorus between the two groups of patients with and without early renal injury indicators. However, the mean levels of serum creatinine and urine creatinine, N-acetyl-β-D-glucosidase enzyme, α1 microglobulin, and urine immunoglobulin in the former group of patients were significantly higher than those in the latter group of patients (P < 0.05). The incidence of early renal injury in patients with eGFR ≥ 90, 60-89, and 30-59 mL/(min·1.73 m2) was 36.4% (8/22), 47.6% (20/42), and 60% (3/5), respectively. Logistic regression analysis results showed that gamma-glutamyl transpeptidase [odds ratio (OR) = 1.05 (1.008-1.093), P = 0.020], direct bilirubin [OR = 1.548 (1.111-2.159), P = 0.010], serum creatinine [OR = 1.079 (1.022-1.139), P = 0.006], and age [OR = 0.981 (0.942-1.022), P = 0.357] were independent predictors of early renal injury. CONCLUSION Patients with CHB treated with long-term nucleos(t)ide analog therapy had a high probability of early renal injury, and early renal injury indicators were highly sensitive and could be used to monitor early renal impairment.

Frailty is a clinical state characterized by an age-related unsteady state of the body, a decline in physiological function, and an increased vulnerability to adverse outcomes. Early diagnosis of frailty is important for improving the quality of life in older adults and promoting healthy aging. The biological mechanisms underlying frailty have been extensively studied in recent years. Combining assessment tools and biomarkers can facilitate the early diagnosis of frailty. However, there is a lack of stable and reliable frailty-related biomarkers for use in clinical practice. Advances in the multi-omics platforms have provided new information on the molecular mechanisms underlying frailty. Thus, identifying biomarkers using omics-based approaches helps explore the physiological mechanisms underlying frailty, and aids the evaluation of the risk of frailty development and progression. This article reviews the current status of frailty biomarkers from the genomics, transcriptomics, proteomics, and metabolomics perspectives.

The advent of the Internet has brought great changes in media use, yet little is known about how media use has changed in China and what leads to the overall media-use changes. Using three waves of...

The use of an optical see-through head-mounted display (OST-HMD) in augmented reality (AR) has significantly increased in recent years, but the alignment between the virtual scene and physical reality is still a challenge. A fast and accurate calibration method of OST-HMD is important for augmented reality in the medical field. We proposed a fast online calibration procedure for OST-HMD with the aid of an optical tracking system. Two 3D datasets are collected in this procedure: the virtual points rendered in front of the observer’s eyes and the corresponding points in optical tracking space. The transformation between these two 3D coordinates is solved to build the connection between virtual and real space. An AR-based surgical navigation system is developed with the help of this procedure, which is used for experiment verification and clinical trial. Phantom experiment based on the 3D-printed skull is performed, and the average root-mean-square error of control points between rendered object and skull model is $$1.30 \pm 0.39$$ mm, and the time consumption of the calibration procedure can be less than 30 s. A clinical trial is also conducted to show the feasibility in real surgery theatre. The proposed calibration method does not rely on the camera of the OST-HMD and is very easy to operate. Phantom experiment and clinical case demonstrated the feasibility of our AR-based surgical navigation system and indicated it has the potential in clinical application.

Hypertension is an important factor affecting the health of older adults. Antihypertensives can reduce stroke, cardiovascular events, and mortality in older hypertensive patients. Blood pressure management is difficult in older adults since geriatric syndromes such as frailty and comorbidities often coexist with hypertension. Recent guidelines propose taking functional status into account when targeting blood pressure in older people. Therefore, a better understanding and control of frailty risk factors could improve the prognosis of older adults with hypertension. However, there are relatively few studies on hypertension and frailty in older adults, especially studies focused on antihypertensive treatment. The goals, target values, and choice of antihypertensive treatment for frail older adults are still disputed. We reviewed the recent literature focusing on frailty and hypertension in older adults and propose a management process for screening and assessing frailty and hypertension before the use of antihypertensives. The process can support older adults with lifestyle interventions and frailty management and help them begin taking a single antihypertensive medication.

Background In our previous study, serine protease inhibitor Kazal-type 5 (SPINK5), which encodes the product of serine protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) was found to be down-regulated in head and neck squamous cell carcinoma (HNSCC) using oligonucleotide microarrays. However, the function and clinical implications of SPINK5/LEKTI remain obscure in HNSCC. Methods The endogenous expression level of SPINK5/LEKTI was further verified in 9 HNSCC cell lines and HNSCCs by means of reverse transcription-polymerase chain reaction, real-time PCR, Western blotting and immunohistochemistry. The biological function of SPINK5/LEKTI was investigated in vitro and in vivo experiments. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to determine the correlation between SPINK5/LEKTI expression and clinical outcome. Results Down-regulation expression of SPINK5/LEKTI was found in six out of nine HNSCC cell lines and in 85.7% HNSCC specimens (P

Objective Normal-weight obesity (NWO) is characterized by high body fat percentage (BFP) in individuals with normal body mass index (BMI). This condition may increase the risk of serious health problems, such as cardiovascular diseases, diabetes, insulin resistance, hypertension, and metabolic syndrome. However, the prevalence of NWO in older adults in Beijing remains unclear. This study aimed to investigate the prevalence of overweight and obesity among older adults in Beijing, using three obesity assessment indicators: BMI, waist circumference, and BFP. Design Cross-sectional study. Setting and participants Data were obtained from the 2012 Beijing Longitudinal Study of Aging, which used a stratified, sectional, random, and cluster sampling method. Methods Questionnaires, physical examinations, and laboratory tests were completed. Obesity was divided into four categories based on combinations of BMI and BFP: non-obese, muscle-type obesity, NWO and fatty obesity. Results A total of 2393 community-dwelling older adults with an average age of 72.98±8.09 years old were recruited. Of them, 1051 were male (43.92%) and 1245 were living in rural areas (52.03%). The prevalence of overweight and obesity among older people in Beijing was 35.5% and 16.1%, respectively. When the sample was divided according to obesity classification, the proportion of muscular obesity, NWO and adipose obesity was 14.7%, 10.7%, and 41.8%, respectively. The prevalence of central obesity was 62.3%. The prevalence of obesity decreased with age, but it was higher in females than in males as well as among individuals living in urban areas than in individuals living in rural areas. Conclusion The prevalence of NWO was 10.7% among older adults in Beijing and increased with age. Older adults who are female or living in urban areas should be instructed to take measures aimed at reducing body fat and increasing muscle strength.

The rapid emergence of antibiotic-resistant bacteria is a threat to global health particularly in the area of healthcare-associate pneumonia (HCAP) where there is high rate of mortality. In general, guidelines should serve as a framework that needs to be complemented by local antibiogram data due to multiple factors influencing the development of multidrug-resistant (MDR) HCAP. Failure to administer prompt and appropriate empirical therapy would often result in a high mortality rate. Based on these concerns, the aim of the study was to evaluate the appropriate empirical use of antibiotic and risk factors of MDR HCAP based on local pathogen resistant pattern. This was a retrospective analysis on HCAP in critical care of a tertiary-care hospital with data from January 2016 to December 2018. Patients diagnosed with HCAP: hospital-associated pneumonia (HAP) and ventilator-associated pneumonia (VAP), with positive bacterial cultures were included into the study. Of the 269 patients and isolates included, 160 (59.5%) had MDR strains. The top causative pathogens isolated were Acinetobacter baumannii (n=104, 38.7%), Pseudomonas aeruginosa (n=66, 24.5%), Klebsiella spp (n==55, 20.4%), and Staphylococcus aureus (n=16, 5.9%). The incidence of inappropriate empirical antibiotic was significantly higher in patients with MDR HCAP (n=135, 84.4%) compared to those with non-MDR HCAP (n=34, 31.2%) (p < 0.001). Mortality was significantly higher in patients receiving inappropriate empirical therapy (n = 118, 72.4%) compared to those receiving appropriate empirical antibiotic (n = 36, 54.5%) (P = 0.009). The independent risk factors for MDR HCAP identified in this study were hypoalbuminemia (odds ratio [OR] 3.43, 95% confidence interval [CI] 1.08 – 10.87, p = 0.036) and indwelling central venous catheter (OR 5.65, 95% CI 1.13 – 28.18, p = 0.035). This work serves as a basis for a center-specific guideline to improve antibiotic use among HCAP patients in intensive care setting.

Banana contains many kinds of substances that are beneficial to depressive symptoms. However, there are no epidemiological researches directly to explore the association between banana consumption and depressive symptoms. This study aimed to investigate whether the banana consumption is related to depressive symptoms in a general adult population.A cross-sectional study was performed in 24,673 adults in Tianjin. Banana consumption was evaluated via a validated food frequency questionnaire. Depressive symptoms were assessed by using Self-Rating Depression Scale (SDS). The association between banana consumption and depressive symptoms was analyzed by multiple logistic regression analysis.The prevalence of depressive symptoms was 16.1% in males and 18.4% in females (SDS ≥ 45), respectively. In males, comparing to the reference group (almost never), the multivariable adjusted odds ratios (ORs) (95% confidence intervals) of depressive symptoms across banana consumption were 0.86 (0.74, 0.99) for1 time/week, 0.76 (0.66, 0.88) for 1-3 times/week and 0.97 (0.82, 1.16) for ≥4 times/week. By contrast, the multivariable adjusted ORs (95% confidence intervals) were 1.11 (0.94, 1.32) for1 time/week, 0.99 (0.85, 1.16) for 1-3 times/week and 1.22 (1.02, 1.46) for ≥4 times/week in females. Similar association was observed when other cut-offs (SDS ≥ 48 and 50) were used to define depressive symptoms.This is a cross-sectional study, causality remains unknown.Findings from this study suggested a negative association between moderate banana consumption and depressive symptoms in males. In females, high banana consumption is positively related to depressive symptoms.

Background Metabolic inflammation plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders often coexist and are closely related with systemic low-grade inflammation. Metabolic inflammatory syndrome (MIS), a cluster of these four metabolic disorders, is a novel concept that is thought to be a better predictor of coronary heart disease than metabolic syndrome. Adiponectin is an adipokine that increases insulin sensitivity and antioxidation as well as has an anti-atherosclerosis effect. It is unclear whether adiponectin is associated with MIS. The objective of this study was to assess whether circulating adiponectin can be used as an indicator for MIS in elderly adults. Methods A total of 136 elderly inpatients were divided into two groups: the MIS group and the non-MIS group. Characteristics, inflammatory markers, blood lipid metabolism, insulin resistance, and circulating adiponectin levels were assessed and compared between the two groups. Logistic regression analysis was used to explore the association between the associated factors and MIS. Results MIS patients were more likely to have a higher body mass index, have a higher fasting blood glucose level, be smokers, have fundus arteriosclerosis, have lower levels of adiponectin (4044.90 ± 3906.82 ng/mL vs 8503.89 ± 3523.89 ng/mL, p < 0.001), and have higher levels of inflammation (white blood cell and C-reactive protein) than non-MIS patients. Multiple factor analysis showed that lower adiponectin levels (OR = 22.937, p < 0.001) were independently associated with MIS. Adiponectin levels were lower in the vascular disease (2673.29 ± 1930.05 ng/mL vs 7194.38 ± 4615.83 ng/mL, p = 0.001), atherosclerosis (2374.14 [1496.41-4263.90] ng/mL vs 6037.48 [3865.61-10,373.60] ng/mL, p < 0.001), and type 2 diabetes (2391.73 [1386.41-4069.68] ng/mL vs 8916.03 [5801.14-12,724.45] ng/mL, p < 0.001) subgroups than in the non-MIS group. Conclusion Lower adiponectin levels in serum are associated with MIS. Low adiponectin may be used as a biomarker for atherosclerosis in patients with MIS.

Ischemia-reperfusion (IR) injury is a major challenge influencing the outcomes of hepatic transplantation. Transforming growth factor-β (TGF-β) and its downstream gene, SMAD family member 3 (Smad3), have been implicated in the pathogenesis of chronic hepatic injuries, such as hepatic fibrosis. Thus, the present study aimed to investigate the role of the TGF-β/Smad3 signaling pathway on hepatic injury induced by IR in vivo. In total, 20 129S2/SvPasCrl wild-type (WT) mice were randomized into two groups; 10 mice underwent IR injury surgery and 10 mice were sham-operated. Histopathological changes in liver tissues and serum levels of alanine aminotransferase (ALT) were examined to confirm hepatic injury caused by IR surgery. The expression levels of TGF-β1, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected via western blotting. Furthermore, a total of five Smad3−/− 129S2/SvPasCrl mice (Smad3−/− mice) and 10 Smad3+/+ littermates received IR surgery, while another five Smad3−/− mice and 10 Smad3+/+ littermates received the sham operation. Histopathological changes in liver tissues and serum levels of ALT were then compared between the groups. Furthermore, hepatic apoptosis and inflammatory cell infiltration after IR were evaluated in the liver tissues of Smad3−/− mice and Smad3+/+ mice. The results demonstrated that the expression levels of TGF-β1, Smad3 and p-Smad3 were elevated in hepatic tissue from WT mice after IR injury. Aggravated hepatic injury, increased apoptosis and enhanced inflammatory cell infiltration induced by hepatic IR injury were observed in the Smad3−/− mice compared with in Smad3+/+ mice. Collectively, the current findings suggested that activation of the TGF-β/Smad3 signaling pathway was present alongside the hepatic injury induced by IR. However, the TGF-β/Smad3 signaling pathway may have an effect on protecting against liver tissue damage caused by IR injury in vivo.

BACKGROUND Ameloblastomas of jaw in the pediatric population are a rare clinical entity and have not been well addressed in the literatures. The present retrospective study analyzed the risk factors associated with recurrence of pediatric ameloblastomas. METHODS Cases of primary pediatric ameloblastomas seen in a tertiary hospital between 2005 and 2015 were analyzed to identify the clinical factors associated with recurrence. RESULTS There were a total of 104 cases of primary pediatric ameloblastomas. The overall mean maximum tumor diameter was 4.11 ± 1.339 cm. The receiver operating characteristic curve and the Youden Index showed an optimal cutoff point of 4.95 cm to accurately predict recurrence. Bone cortex/soft tissue invasion were associated with tumor recurrence (P

Purpose We report our experience of intensity‐modulated proton and carbon‐ion radiotherapy (IMPT/IMCT) for head and neck sarcomas (HNS). Methods and Materials An analysis of the ongoing prospective data registry from the Shanghai Proton and Heavy Ion Center (SPHIC) for patients with HNS was conducted. The 12‐ and 24‐month rates of local recurrence‐free, overall, distant metastasis‐free, progression‐free survival (LRFS, OS, DMFS, and PFS), and acute/late toxicities were calculated. The prognostic factors for the effectiveness of the treatment were also analyzed. Results Between 7/2014 and 5/2018, 51 consecutive patients with HNS received definitive doses of IMCT (41 cases), IMPT (two cases), or their combination (eight cases). One patient had R0 resection and another treated on the Chinese Food and Drug Administration registration trial received IMPT only. Twenty‐seven patients were treated according to various dose escalation trials or institutional protocols using IMCT or IMPT + IMCT boost. Twenty‐two patients with locoregional recurrence (10 and four patients failed surgery or surgery followed by radiotherapy, respectively) or radiation‐induced second primary sarcomas (eight patients) received salvage particle radiotherapy. With a median follow‐up time of 15.7 months, four patients with second primary sarcoma died. The 1‐ and 2‐year OS, PFS, LRFS, and DMFS rates for the entire cohort were 92.9% vs 90%, 73.6% vs 57.4%, 88.4% vs 78.9%, and 84.6% vs 76.5%, respectively. Those rates for patients without prior radiotherapy were 100% vs 100%, 82.1% vs 65.8%, 93.6% vs 85.3%, and 88.4% vs 79.5%, respectively. Multivariate analyses revealed that re‐irradiation was an independent prognostic factor for both LRFS and PFS (P = 0.015 and 0.037, respectively). In addition, gross tumor volume (GTV) was an independent prognostic factor for PFS (P = 0.048). One patient experienced Grade 3 acute toxicity (oral mucositis); another experienced Grade 4 acute event (hemorrhage) which required embolization. He lately died from hemorrhage (Grade 5) at 3.4 months after the completion of treatment. No patient experienced radiation‐induced acute/late toxicity of ≥ Grade 2 otherwise. Conclusion With few observed acute/late toxicities, IMPT/IMCT provided effective short‐term tumor control in our patients with HNS. Further investigations, preferably in a prospective fashion, will be required to confirm the efficacy and toxicities of IMPT/IMCT in this group of patients.

The requirement for detecting faulty equipment is widespread in the industry. In today's big data era, using big data features to detect equipment is facing new opportunities and challenges. In order to improve the efficiency of faulty equipment detection, we found the characteristics of the binary tree that are suitable for manufacturing processes of the current status. In practice, this paper establishes a binary tree model for the manufacturing process. Then, in order to analyze and study the breadth traversal process and depth traversal process of bad nodes in binary tree, this paper proposes a location method of breadth and depth ratio. Finally, the location range of the faulty equipment (bad node) is quickly found due to the influence of breadth and depth ratio. The experimental results show the difference between the existing mechanisms of detection and position. In terms of accuracy and efficiency, both methods of deep traversal and breadth traversal have their own advantages in different devices and processes. To compare with the two methods, the detection method of breadth and depth ratio in this paper has the characteristics of higher efficiency, feasibility and accuracy.

Li Zhang,1,2,&ast; Tong Ji,1,2,&ast; Fei Sun,2 Yun Li,1 Zhe Tang,1,2 Lina Ma1,2 1Department of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Beijing Geriatric Healthcare Center, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lina Ma; Zhe Tang Email malina0883@126.com; tangzhe@sina.comObjective: The comprehensive geriatric assessment (CGA) is an integral tool used to identify vulnerable older adults in need of individualized plans to delay the course of diseases and monitor treatment outcomes. We previously developed and validated a 68-item frailty index (FI) based on the CGA in a large, older, Chinese population. However, substantial time is needed to evaluate the 68 items. Therefore, we aimed to develop and validate a simplified FI for use in Chinese older population.Design: Longitudinal study.Setting and Participants: Data were drawn from the Beijing Longitudinal Study of Aging. The study was conducted in 2004 with 1808 participants evaluated using the CGA and was followed-up for 13 years. Mortality was recorded at 3, 5, 8, 10, and 13 years intervals.Measures: 27-Item, 50-item, and 68-item frailty indices were investigated. A Cox proportional hazards model and area under the curve of the receiver operating characteristic (AUC-ROC) were calculated to compare mortality predictions.Results: The FI was positively correlated with age in males (r = 0.174, P < 0.001) and females (r = 0.270, P < 0.001). The mean baseline FI was 0.225 ± 0.085 (range: 0.04– 0.56) as evaluated by the 27-item FI, 0.181 ± 0.117 (range: 0.02– 0.62) by the 50-item FI, and 0.167 ± 0.101 (range: 0.02– 0.59) by the 68-item FI. Cox regression models showed that mortality was significantly higher in frail people than in non-frail people for all 3 indices (p< 0.001). The AUCs of the 68-item FI, 50-item FI, and 27-item FI for predicting mortality were 0.720, 0.717, and 0.677, respectively (p< 0.001).Conclusion: The 27-item FI is reasonable to expect that the AUC of the indices with the higher items number is inferior to the performance of the indices with higher number of items (FI50 and FI68). But 27-item maybe used as a tool to identify frail older adults and predict mortality in clinical and primary care practices in China.Keywords: frailty index, older adults, comprehensive geriatric assessment, mortality

Objectives Hypertension is highly prevalent in the elderly and represents a major risk factor for cardiovascular complications such as coronary heart disease, stroke, and cognitive dysfunction. Frailty is a common geriatric syndrome characterized by increased risk of disability, hospitalization, and mortality. However, little is known about the frailty status in older adults with hypertension. Thus, we aimed to explore the epidemiological characteristics and related factors of frailty in older Chinese adults with hypertension. Methods The current study included data collected from participants in the China Comprehensive Geriatric Assessment Study. Frailty was defined using the frailty index. Hypertension was defined as SBP at least 140 mmHg, DBP at least 90 mmHg, current treatment with antihypertensive medication, or a self-reported diagnosis of hypertension. Results Frailty index was positively correlated with age. The prevalence of frailty was significantly higher in hypertensive patients than in normal controls. The prevalence of frailty in older adults with hypertension was 13.8% in China. The awareness and treatment of hypertension was higher in frail individuals than in nonfrail individuals. The control rate of hypertension did not differ significantly between the two groups. Logistic analysis showed that older age, poor marital status, coronary heart disease, chronic obstructive pulmonary disease, cerebrovascular disease, diabetic mellitus, osteoporosis, hearing loss, lack of exercise, depression, cognitive impairment, and higher white blood cell count were factors independently related with frailty in older participants with hypertension. Conclusion The current study provides the first evidence regarding the status of frailty in older Chinese adults with hypertension.

Objectives The aim of this study was to retrospectively analyze the clinical characteristics, surgical treatment, and prognosis of patients with diffuse-type tenosynovial giant cell tumor (D-TGCT) involving the temporomandibular joint (TMJ) and the skull base. Study Design A retrospective study was performed in patients with D-TGCT involving the TMJ and the skull base at our institute from April 2009 to August 2018. Data on clinical characteristics, surgical treatment, and prognosis were collected and analyzed. A literature search on D-TGCT involving the TMJ was conducted and the data analyzed. Results The study included 22 patients (14 males and 8 females), with an average age of 44 years. The main symptoms were headache and hearing limitation, accompanied by a swelling in the TMJ area. Magnetic resonance imaging (MRI) showed low signals on T1- and T2-weighted images. All lesions were completely removed. Temporal bone flap, titanium mesh, and temporal muscle flap were used for reconstruction. The recurrence rate was 4.5%. In the literature, 115 cases were reported. Surgery alone was performed in 88 cases; postoperative radiotherapy was performed in 19 cases; the tumor recurrence rates were 9.1% and 15.8% for the 2 procedures, respectively. All patients were alive at the end of the follow-up period. Conclusions D-TGCT involving the TMJ and the skull base is a locally aggressive but benign lesion necessitating complete resection and has a good prognosis.

Nerves have been widely demonstrated to exert major effects in tumor-associated microenvironments. Due to the characteristic innervation of the oral cavity and the fact that cancer-associated pain is a distinct feature of oral squamous cell carcinoma (OSCC), the sensory nerves may dominate in the OSCC-nerve microenvironment. As the most abundant neuropeptide in the trigeminal ganglion, the calcitonin gene-related peptide (CGRP) exerts a dual effect on cancer development and cancer-associated pain in various types of cancer. The present review explored the potential molecular mechanisms of the roles of CGRP in cancer development and cancer-associated pain, suggesting that CGRP may be a promising therapeutic target for OSCC.

Background and Aims: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A recent randomized phase III trial of combined immunotherapy (atezolizumab) with antiangiogenesis (bevacizumab) versus the standard sorafenib monotherapy reported an unprecedented response rate of 27%, leading to FDA approval of this combination as the new standard treatment in May 2020. Yet, despite this undisputable progress, the majority of the HCC cases are likely to recur or develop resistance to both first line therapy. In this study, we aimed to identify novel, druggable candidate genes for patients with sorafenib resistant HCC. Method: CRISPR/Cas9 genome (GeCKO v2) library screening was used to identify loss of function mutations conferring sorafenib resistance upon HCC cells. CCK-8 and clonogenic assays were used to measure cell viability and cytotoxicity. Flow cytometry was performed to analyze cellular reactive oxidative species (ROS) and apoptosis level. Multiple animal models were used to study the synergistic efficacy of the combination of nuclear factor erythroid 2- related factor 2 (NRF2) inhibition and sorafenib. Results: In our study, we explored the mechanisms underlying sensitivity of HCC cells to sorafenib using genome-wide CRISPR-Cas9 screening. Kelch-like ECH- associated protein-1(KAEP1) was discovered as a previously unknown factor for determining the sensitivity of HCC cells to sorafenib. Using established sorafenib resistant HCC cell lines and the parental cell, we validated that KEAP1 mediates NRF2 degradation through the ubiquitin-proteasome pathway, thereby conferring sensitivity to sorafenib. Conversely, the loss of function of KEAP1 reduced degradation of NRF2 and conferred increased sorafenib resistance. Analysis of 55 patients with HCC, who had received hepatic resection followed by postoperative standard sorafenib treatment, revealed that high NRF2 expression shortened both overall survival (P Conclusion: Our results uncovered the potential of NRF2 as a drug target for patients with sorafenib resistant HCC. The impressive efficacy of NRF2 inhibitor and sorafenib suggests a potential combination therapy to supplement the existing standard of treatment for sorafenib resistant HCC. Citation Format: Jiang Chen, Shi Jiang, Bixia Li, Tong Ji, Staiculescu Daniel, Jiayan He, Junjie Xu, Xiujun Cai. Small molecule inhibitor of NRF2 selectively overcomes sorafenib resistance in KEAP1-deficient hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1419.

Background Osteosarcoma is an aggressive bone malignancy presenting uncommonly in head and neck sites. Surgery is mainstay in treatment. However; trials show an improved survival with addition of chemotherapy in the treatment of extremity osteosarcoma. The head and neck osteosarcomas(HNOs) were excluded in these trials because of atypical presentation and disease course. Further; sufficient numbers were not possible for a trial. We present the largest retrospective study from single institute investigating the role of chemotherapy in the management of HNOs. Patients and methods The retrospective cohort of HNOs treated from 2007 to 2015 of a tertiary hospital were charted. The therapeutic and prognostic factors were analyzed for overall survival(OS), disease free survival(DFS), local control(LC) and metastasis(MT) in univariate and multivariate analysis. The minimum and median period of follow up was 12 months and 56.04 months respectively. Results There was a total of 157 patients definitively treated with surgery in the time period. 7 patients had positive margins and all were maxillary or skull base tumors. The multivariate cox regression showed significance of tumor site(p = 0.034), margin status (p = 0.006), chemotherapy(p = 0.025), histological subtype(p = 0.012) as predictors of overall survival. The margin status(p = 0.002), Radiotherapy(p = 0.005) were significant predictors for local recurrence. The age and histology subtype(p = 0.058) were borderline significant predictors of metastasis(p = 0.065). The KM method for OS of different chemotherapy groups(p = 0.013), and survival with and without chemotherapy(p = 0.007) was significant. The OS was significantly better with adjuvant chemotherapy among various treatment plans(p = 0.034). Conclusion Adjuvant chemotherapy improved OS while adjuvant radiotherapy improved local control of HNOs.

We aimed to identify and evaluate the clinical challenges involved in microvascular flap reconstructions of defects caused by resection of head and neck cancer among patients aged 85 and over. We designed a retrospective study of patients who were treated in the head and neck department of a tertiary referral centre from 2005 to 2015, and all patients aged 85 years and over who had reconstructions with microvascular flaps for head and neck cancer were entered into the study. A total of 24 patients fulfilled the criteria, of whom 15 were men and nine were women. The median (range) duration of stay in hospital was 23 (14-59) days. Eighteen patients had an American Society of Anesthesiologists (ASA) score grade II and six patients grade III. The median (range) operating time was 420 (310-705) minutes, and operative blood loss 550 (200-1500) ml. Sixteen patients had prophylactic tracheostomies, nine of whom developed postoperative surgical complications, seven associated with the tracheostomy (p = 0.005). Resections of head and neck cancer and microvascular reconstructions in patients aged 85 and over are associated with a high incidence of postoperative complications. Medical complications tend to be associated with the tracheostomy while surgical complications are potentially associated with the ASA score. Although the morbidity is high, complex resections and microvascular reconstructions are successful with optimum recovery, and age did not seem to influence the outcome. However, it is necessary to avoid prophylactic tracheostomy if possible in these patients.

Background Venous thromboembolism (VTE) is a preventable complication in which early ambulation is expected after head and neck surgery. Thus, the role of VTE prophylaxis is questionable and needs further assessment. The purpose of this study was to specify the relative contributing risk factors for patients who underwent head and neck cancer ablation with immediate reconstruction. Methods A retrospective analysis was conducted of consecutive head and neck cancer ablations with immediate reconstructions between 2008 and 2013. Dextran and prostaglandin E2 (PGE2) were routinely given as flap thromboprophylaxis. Logistic regression was applied to analyze the potentially significant risk factors. Results Of 1953 subjects, the incidence of symptomatic VTE was 2.2% with 0.1% mortality rate. Prolonged surgery (>592.5 minutes; P = .048), immobilization (>4 days; P = .019), and subjects without postoperative flap thromboprophylaxis (P = .002) are significant risk factors for VTE development. Conclusion Our flap thromboprophylaxis regime might have played a crucial role in keeping the incidence of VTE low. Despite prolonged immobilization in fibula flap reconstruction, the incidence of VTE remained low when flap thromboprophylaxis was given.

Background Maxillary ameloblastomas are rare and associated with an aggressive course because of the anatomic composition of the maxilla and adjacent structures. The risk factors associated with recurrence were analyzed in this retrospective study. Methods Cases of maxillary ameloblastoma reported in a tertiary hospital from 2005 to 2015 were analyzed to identify clinicopathological and radiological factors associated with recurrence using univariate and multivariate Cox regression analyses. Results A total of 890 patients with ameloblastomas were treated in this study, of whom only 51 (5.7%) had maxillary ameloblastomas. The median follow-up period was 56 ± 28.65 months. Of the maxillary ameloblastomas, 29 (56.8%) were primary and 22 (43.1%) were recurrent. Soft tissue or maxillary sinus invasion and primary or recurrent tumor status were risk factors significantly associated with recurrence in the univariate analyses (p = .006 vs p = .025, respectively), whereas the association between recurrence and surgical methods was borderline significant (p = .08). The multivariate Cox regression analysis showed that soft tissue or maxillary sinus involvement was significantly associated with recurrence (p = .023). Conclusion Recurrent tumors and tumors with soft tissue or maxillary sinus involvement were risk factors for recurrence among patients with maxillary ameloblastoma. © 2017 Wiley Periodicals, Inc. Head Neck 39: 996–1000, 2017

Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome study, we identified eIF4EBP3 as a methylated gene in GC. However, the role of eIF4EBP3 in GC progression has not been explored. The expression and promoter region methylation of eIF4EBP3 in GC and healthy tissues were analyzed in public datasets. eIF4EBP3 expression in GC was detected by semi-quantitative RT-PCR, western blot and immunohistochemistry. We also studied epigenetic alterations and functions in GC. The effects of eIF4EBP3 on cell proliferation, migration and invasion were conducted by functional experiments in vitro and in vivo. Label-free proteomic analysis was applied to identify targets of eIF4EBP3. The expression level of eIF4EBP3 was downregulated in gastric cancer due to promoter region methylation, and was associated with poor survival and tumor progression. Ectopic expression of eIF4EBP3 significantly inhibited tumor cell growth, migration and invasion both in vitro and in vivo. Label-free proteomic analysis indicated eIF4EBP3 downregulated the protein level of β-catenin, which was confirmed by western blot. Overexpression of β-catenin reversed the inhibitory effects of eIF4EBP3 on cell growth and migration, indicating that eIF4EBP3 acts on GC cells by targeting the eIF4E/β-catenin axis. These results suggest that eIF4EBP3 is a novel TSG methylated in gastric cancer that may play important roles in GC development and liver metastasis and indicate eIF4EBP3 as a potential metastasis and survival biomarker for GC.

Objective The aim of this study was to unveil the reciprocal relation of tumor characteristics and inflammation in inflammatory myofibroblastic tumor in the head and neck. Study Design The study included a retrospective cohort of patients with inflammatory myofibroblastic tumors treated between 2005 and 2017 in a tertiary hospital. Tumor features and inflammation were assessed through the expression of anaplastic lymphoma kinase (ALK), the degree of inflammation and cyclooxygenase-2 (COX-2) expression. The prognostic factors were analyzed for overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. Results Forty-one patients diagnosed with inflammatory myofibroblastic tumors were followed up, and 41 paraffin sections were obtained. The positive rate of ALK expression was 21 (51.2%) of 41 patients. Nineteen patients had high-grade ALK expression, and 22 patients had low-grade ALK expression. Thirty-nine patients had high-grade inflammation, and 2 had low-grade inflammation. The positive rate of COX-2 expression was 100%. Tumors with both high-grade ALK expression and inflammation had worse DFS (P = .015). The multivariate Cox analysis showed that the grades of ALK expression and inflammation (P = .004) were independent risk factors for DFS. Conclusions Because of the latent synergistic effects of ALK and inflammation in the tumorigenesis of inflammatory myofibroblastic tumor, the combined therapy of ALK and COX-2 inhibitors shows promise.

Understanding the molecular mechanisms regulating tumor dissemination and therapeutic resistance is of central importance for effective cancer therapies. Here, we report that nerve growth factor (NGF) and its receptor TrkA facilitate epithelial-mesenchymal transition (EMT) and EGFR inhibitor resistance via STAT3 activation in head and neck squamous cell carcinoma (HNSCC). Both NGF and TrkA expression were elevated in HNSCC, indicating poor clinical outcomes. NGF was highly expressed in cancer cells and nerves in perineural niche, whereas TrkA expression was higher in cancer cells with perineural invasion. The NGF/TrkA axis could promote HNSCC cell dissemination and trigger EMT via STAT3 activation. Moreover, we discovered that the NGF/TrkA axis conferred resistance to the EGFR inhibitor erlotinib via EMT processes in HNSCC cells. Blocking TrkA signaling markedly reversed EMT and sensitized HNSCC cells to erlotinib in both in vitro and in vivo models. Overall, our results demonstrate novel evidence that the paracrine NGF/TrkA axis favors EMT and confers EGFR-targeted therapeutic resistance in HNSCC.

This study aims to examine the relationship among the Dark Triad personality traits, Internet use preferences and Internet adaptation. In all, 1927 middle school students (aged 11–18) from Beijing and Kunming in China completed a self-reported questionnaire that measured the Dark Triad, Internet use preferences (information communication, recreation, information acquisition and online transaction) and Internet adaptation (positive/negative Internet adaptation). Correlations revealed that there were significant correlations among the Dark Triad, Internet use preferences and Internet adaptation. Multiple regression analysis indicated that psychopathy predicted Internet adaptation more significantly than Machiavellianism or narcissism. Information acquisition positively predicted positive Internet adaptation and negatively predicted negative Internet adaptation, and recreation and online transaction were just the opposite. The SEM results suggested that Internet use preferences partially mediated the relationship between the Dark Triad and Internet adaptation. We discussed the importance of the combined effect of the Dark Triad and Internet use preferences on Internet adaptation.

Free flap reconstruction after resection in paediatric patients with head and neck cancer (HNC) has various clinical challenges, which have not yet been fully investigated. This retrospective study was implemented to investigate these factors. Paediatric patients (≤14 years old) who underwent free flap reconstructions following surgery for HNC at a tertiary referral centre during the years 2009–2018 were included. Clinical, pathological, and imaging data were collected and analysed. Overall, 47 patients were included, 26 male and 21 female. Thirty-four patients were ASA status I and 13 were ASA status II. The median operative time was 415 minutes, while the median intraoperative blood loss was 500 ml. Seventeen patients had a tracheotomy. Fourteen medical complications (six pulmonary infection, six diarrhoea, two pulmonary aspiration) and six surgical complications (one haematoma beneath flap, two wound dehiscence, one salivary fistula, one effusion, one tracheotomy haemorrhage) were observed. Tracheotomy was associated with medical complications (P = 0.003) and total complications (P = 0.024). It was confirmed that microvascular reconstruction can be adopted in paediatric HNC patients, while tracheotomy and nasal feeding tubes should be used with caution. Comprehensive preoperative assessment, gentle handling of the tissues during operative procedures, and appropriate postoperative management will reduce the risk of complications.

Vascular anastomosis is the most important technical step required for the possibility of free tissue transfer, and mismatch of the donor and recipient vessel size is the most common surgical challenge. As recent reports have described a new method (Ren anastomosis) to resolve this challenge, the goal of this study was to assess these newly described microvascular anastomosis methods.The study was conducted at 2 institutes in China in different periods. Patients were recruited from the Second Xiangya Hospital between February and May 2013 and from the Shanghai Ninth People's Hospital between March and May 2015. All patients who participated in this study needed free flaps for oral and maxillofacial defects. Patients were divided into the experimental group and the control group. In the experimental group, isometric double-notch end-in-end microvascular anastomosis (Ren anastomosis) was performed, whereas end-to-end anastomosis was performed in the control group. Statistical differences were assessed by use of χA total of 148 patients (108 men and 40 women) were treated over the course of this study. There was a statistically significant difference (P.001) in the operation time for the microscopic artery anastomosis between the experimental group (70 cases; 5.6 ± 1.8 minutes) and the control group (78 cases; 14.6 ± 3.7 minutes). In each group, 1 case of artery compromise was observed.The Ren anastomosis was time-saving, straightforward, efficient, and easy to learn, with a high patency rate.

In this paper, variation tendency of phosphorylated Nrf2, as the activated form of native Nrf2, was studied in 107 primary hepatocellular carcinoma (HCC) specimens treated by curative hepatectomy. Moreover, the coexpression of oxidative stress markers Keap1 and pNrf2, and their association with pathological features were also evaluated based on those specimens. The results showed that preserved cytoplasmic Keap1 expression of cancer cells was observed in 59 HCCs, while reduced Keap1 expression was determined in remaining 48 ones. With regarding to nuclear pNrf2 expression, 75 HCCs were defined as high and the other 32 ones as low. There was a significant association between Keap1 and pNrf2 expression in HCCs. Higher pNrf2 expression was observed, at a more substantial proportion, in those specimens with reduced Keap1 expression, compared to those with preserved Keap1 expression. The subset with higher pNrf2 and reduced Keap1 expression was defined as pNrf2+ Keap1−. According to the analysis of prognosis, this subset was significantly associated with poor 5‐year overall survival and worse disease‐free survival in HCCs, indicating that pNrf2 and Keap1 were two‐functional biomolecules, not only the oxidative stress markers but also biomarkers for prognosis of HCCs.

Smoking tobacco is the main risk factor for head and neck cancer, is proportional to the number of pack years (number of packs smoked/day x number of years of smoking), and is reduced when the patient stops smoking. Current molecular evidence has suggested that tobacco-related cancers could be clinically more aggressive than cancers in non-smokers, particularly in the head and neck. However, clinical studies have not uniformly reproduced the relation between survival and tobacco, possibly because they ignore the health benefit that reformed smokers obtain during the period between giving up smoking and the diagnosis of cancer, which is not shared by those who continue to smoke and develop cancer. We have investigated the survival of reformed smokers, non-smokers, and continuing smokers after a diagnosis of head and neck cancer. The data of patients with head and neck cancer from 1992 -2013 from the Cancer Genome Atlas database were analysed using a multivariate Cox's regression model for survival, and Kaplan-Meier curves were produced for smoking history. A total of 521 patients were treated for head and neck cancer, and there was a significant difference in survival between reformed and non-smokers on the one hand, and current smokers on the other (p=0.02). The significance increased when reformed smokers were grouped according to their duration of abstinence and time of diagnosis of cancer (15 and ≤15 years, p0.01). Smoking history was a significant prognostic factor in the multivariate Cox's regression model when analysed with age, stage, grade, and site. We conclude that reformed smokers have a survival benefit in head and neck cancer.

// Zhen-Hu Ren 1, 2, * , Cheng-Zhong Lin 1, 2, * , Wei Cao 1, 2 , Rong Yang 1, 2 , Wei Lu 1, 2 , Zhe-Qi Liu 1, 2 , Yi-Ming Chen 1, 2 , Xi Yang 1, 2 , Zhen Tian 3 , Li-Zhen Wang 3 , Jiang Li 3 , Xu Wang 1, 2 , Wan-Tao Chen 1, 2 , Tong Ji 1, 2 , Chen-Ping Zhang 1, 2 1 Department of Oral Maxillofacial-Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China 2 Shanghai Research Institute of Stomatology and Shanghai Key Laboratory of Stomatology, Shanghai 200011, China 3 Department of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China * These authors contributed equally to this work Correspondence to: Chen-Ping Zhang, email: zhangcp9th@hotmail.com Tong Ji, email: jitong70@hotmail.com Keywords: CD73, adenosine receptor, EGFR, EMT, head and neck squamous cell carcinoma Received: April 18, 2016 Accepted: July 28, 2016 Published: August 20, 2016 ABSTRACT CD73 is a cell surface immunosuppressive enzyme involved in tumor progression and metastasis. While patients whose cancer cells express elevated CD73 are typically associated with an unfavorable outcome, the clinical impact of CD73 expression in patients with Head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, we investigated the prognostic significance of CD73 in HNSCC using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with reduced overall survival in patients with HNSCC. We also investigated the functional role of CD73 in vitro and demonstrated that CD73 promotes HNSCC migration and invasion through adenosine A3R stimulation and the activation of EGF/EGFR signaling. Moreover, in vivo xenograft studies demonstrated that CD73 promotes tumorigenesis. In conclusion, our study highlights a role for CD73 as a poor prognostic marker of patient survival and also as a candidate therapeutic target in HNSCCs.

// Tong Ji 1, 2, * , Gaofeng Li 1, * , Jiang Chen 2, * , Jie Zhao 2 , Xi Li 3 , Hui Lin 2 , Xiujun Cai 2 , Yong Cang 1 1 Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, China 2 Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China 3 Oncology Business Unit and Innovation Center for Cell Signaling Network, WuXi AppTec Co., Ltd., Shanghai 200131, China * These authors contributed equally to this work Correspondence to: Yong Cang, email: cangyong@zju.edu.cn Xiujun Cai, email: cxjzu@hotmail.com Keywords: IL6, TNFR1, oval cell, hepatocellular carcinoma, NK cell Received: January 01, 2016 Accepted: August 08, 2016 Published: August 18, 2016 ABSTRACT Interleukin 6 (IL6), tumor necrosis factor α (TNFα) and TNF receptor-1(TNFR1) have been shown to involve in oval cell proliferation and hepatocellular carcinoma (HCC) development. However, their role in these processes is still unclear. In the present study, by using hepatocytes-specific DDB1 deletion mouse models, we explored the role and mechanism of IL6, TNFα and TNFR1 in oval cell proliferation and HCC development in the context of inflammation, which is the common features of HCC pathogenesis in humans. Our results showed that IL6 promotes oval cell proliferation and liver regeneration, while TNFα/TNFR1 does not affect this process. Deletion of IL6 accelerates HCC development and increases tumor burden. The number of natural killer(NK) cells is significantly decreased in tumors without IL6, implying that IL6 suppresses HCC by NK cells. In contrast to IL6, TNFR1-mediated signaling pathway promotes HCC development, and deletion of TNFR1 reduced tumor incidence. Increased apoptosis, compensatory proliferation and activation of MAPK/MEK/ERK cascade contribute to the oncogenic function of TNFR1-mediated signaling pathway. Intriguingly, deletion of TNFα accelerates tumor development, which shows divergent roles of TNFα and TNFR1 in hepatocarcinogenesis.

// Jiang Chen 1, 2, * , Tong Ji 2, * , Jie Zhao 1, 2 , Gaofeng Li 2 , Jian Zhang 1 , Renan Jin 1 , Jinghua Liu 1 , Xiaolong Liu 1 , Xiao Liang 1 , Diyu Huang 1 , Anyong Xie 1, 3 , Hui Lin 1 , Yong Cang 2 , Xiujun Cai 1 1 Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China 2 Life Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, Zhejiang, 310029, China 3 Institute of Translational Medicine, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China * These authors have contributed equally to this work Correspondence to: Xiujun Cai, e-mail: cxjzu@hotmail.com Yong Cang, e-mail: cangyong@zju.edu.cn Hui Lin, e-mail: 369369@zju.edu.cn Keywords: hepatocellular carcinoma(HCC), phosphorylated extracellular signaling-regulated kinase(pERK), programmed death receptor-1 (PD-1), sorafenib Received: December 25, 2015 Accepted: March 31, 2016 Published: April 25, 2016 ABSTRACT Sorafenib is a multikinase inhibitor approved as the first line treatment for late stage hepatocellular carcinoma (HCC). Due to its significant variation in clinical benefits among patients, defining prognostic biomarkers for sorafenib sensitivity in HCC would allow targeted treatment. Phosphorylated extracellular signaling-regulated kinase (pERK) was proposed to predict the response to sorafenib in HCC, but clinical supports are mixed or even contradictory. Here we found that pERK expression levels are variable in different nodules from individual patient liver. Xenografts derived from resected tumors are resistant to sorafenib inhibition when expressing low levels of pERK. This correlation of low pERK levels and sorafenib resistance is corroborated by histological characterization of chemical-induced and genetic mouse models for pERK-positive and pERK-negative HCC respectively, as well as computed tomography (CT) imaging of patient tumors with validated pERK expression. Mouse and human HCC samples expressing low pERK show strong inflammatory infiltrating cells and significant enrichment of intratumoral CD8 + cytotoxic T lymphocytes that express programmed death receptor-1 (PD-1). These pERK - PD-1 + patients have poorer overall and disease-free survival than pERK + PD-1 - patients. In conclusion, our data suggest that anti-PD-1 immunotherapy might complement sorafenib in treating HCC patients by targeting sorafenib-resistant cancer cells, and the dual pERK and PD-1 biomarkers would help HCC patient selection to achieve optimal clinical benefits.

This retrospective study was performed to review 1038 patients who underwent mandibular reconstruction with free vascularized bone flaps at a single institution between 2006 and 2017. Of these patients, 827 (79.67%) had fibula flaps, 197 (18.98%) had deep circumflex iliac artery perforator (DCIA) flaps, and 11 (1.06%) had scapula bone flaps. The most common pathological diagnosis was ameloblastoma (n=366, 35.26%), followed by squamous cell carcinoma (n=278, 26.78%) and osteoradionecrosis (n=152, 14.64%). Fifty-seven patients (5.49%) had major complications requiring surgical intervention and one patient died of a pulmonary embolism. Venous crisis was the most frequent major complication (n=20, 1.93%), followed by haematoma (n=17, 1.64%) and flap necrosis (n=14, 1.35%). One-stage mandibular reconstruction was preferred whenever possible, as this generally decreases the financial and hospitalization burden. The four-segment method of jaw reconstruction appeared to achieve good aesthetic appearance results in Asian patients and this was not associated with a higher risk of segment ischemia compared with the three-segment method.

The aim of this study was to compare the outcomes of elective neck dissection (END) with that of a more conservative approach comprising of observation plus therapeutic neck dissection for nodal relapse (OBS), by conducting a meta-analysis of randomized controlled trials (RCTs) that compare these two surgical approaches in patients. RCTs conducted prior to May 2015 were identified from electronic databases such as MEDLINE EMBASE and Cochrane Library. Reference lists within the retrieved articles were used as secondary reference sources. Disease-free survival (DFS) and overall survival (OS) were the primary outcome measures. Five RCTs with a combined subject population of 779 patients were included. Meta-analysis of these 5 RCTs showed that DFS in END group was higher than that in the OBS group with a significant inter-group difference (Risk Ratio [RR]:1.33; 95% Confidence Interval [CI] 1.06, 1.66); P=0.01; five trials, 779 participants]. However, there was a significant statistical heterogeneity among the studies (I-squared=56%, P=0.06). Four studies had reported on OS. Meta-analysis of these 4 RCTs revealed a higher OS in the END group as compared to that that in the OBS group with a significant inter-group difference (RR: 1.18; 95% CI 1.07, 1.29); P=0.0009; four trials, 708 participants]. The statistical heterogeneity of these 4 studies is small (I-squared=14%, P=0.32). The results of this meta-analysis suggest that END at the time of resection of the primary tumor confers a DFS and OS benefit in patients with clinically node-negative oral cancer.

Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC.

Objectives To summarize the clinical features, diagnosis, treatment strategies, and prognosis of alveolar soft part sarcoma (ASPS) of the oral and maxillofacial region. Study design We performed a retrospective study in a consecutive series of 18 patients with ASPS of the oral and maxillofacial region between 1995 and 2013. Demographic characteristics, tumor sizes, sites, tumor metastasis, diagnosis, treatments, and overall follow-ups were documented. Results The 18 patients were diagnosed pathologically with primary tumor developed on the tongue (10), the cheek (5), the pharynx (1), and the gingiva (2) with an average tumor size of 4 cm. At the latest follow-up, 1 patient with lung metastases survived for 23 months; 1 died 3 months after the confirmation of local recurrence and multiple pulmonary metastases; the rest of the patients were disease free and remained in good health. Conclusions ASPS of the oral and maxillofacial region appears to have special clinical characteristics.

BACKGROUND The vascular fibula flap is an ideal choice for function and appearance reconstruction of mandible. Despite the high success rate, "late complications" such as Ti plate exposure and local infection related to osteosynthesis are not uncommon. PATIENTS AND METHOD A retrospective cohort of patients who received vascular fibula reconstruction for mandible from January 2011 to December 2013 from the Department of Oral and Maxillofacial Oncology in a tertiary hospital were charted: clinical, pathological, and therapeutic factors were analyzed for late complications in univariate and multivariate analyses. RESULTS One hundred forty-two patients were finally analyzed with median follow-up time of 47 months; 19 of them had "late complications," which occurred at a median of 8 months. Preoperative or postoperative radiotherapy (P = 0.02), type of Ti plate (P = 0.019), and the disease characteristics (P = 0.02) were significant factors on univariate. Cox regression suggested postoperative radiation (P = 0.009) and smoking history (P = 0.037) were independent significant factors for late complications. Secondary reconstruction (P = 0.069) and preoperative radiotherapy (P = 0.086) were borderline significant. CONCLUSION Postoperative radiation and smoking history are associated with late complications. Mini Ti plate should be less used. Patients with risk factors need to be observed for at least 6 to 16 months before further management.

Sorafenib, the only approved drug for hepatocellular carcinoma, acts as a remarkable inhibitor of Raf serine‐threonine kinases. However, Sorafenib is expensive, and clinical experience shows that it is not an effective treatment for many patients. Previous study has demonstrated that phosphorylated ERK (pERK) is a key downstream component in the RAF/MEK/ERK signaling pathway. Here, we investigate whether pERK is a useful biomarker for treating HCC with Sorafenib. In vitro cell viability assays showed that the efficacy of Sorafenib was distinctly different according to the level of pERK. Furthermore, in established patient‐derived xenografts from HCC specimens, we found that the growth rate of tumors with high levels of pERK was significantly decreased by Sorafenib treatment. Taken together, pERK is a potential biomarker for the sensitivity to Sorafenib in treating HCC.

To establish the prognostic factors for primary intraosseous squamous cell carcinoma we designed a retrospective study of patients treated in the head and neck department of a tertiary referral centre in China from 2010-2015. We collected clinical, radiological, and histopathological data from 36 patients treated during the given time period, among which 34 were followed up. There were 22 male and 12 female patients, 13 of whom gave a history of smoking tobacco and four who drank alcohol. All 34 patients were treated by segmental mandibulectomy and neck dissection. Nine had cervical lymph node metastases on histopathological examination, and none had invaded surgical margins. Twenty-eight were treated with radiotherapy postoperatively. During follow up nine died of locoregional recurrence or metastases. Specific factors such as cervical lymph node metastases were related to a greater likelihood of locoregional recurrence. Patients who drank alcohol were also more likely to develop metastases postoperatively. Tumours more than 4cm in size were significantly associated with reductions in locoregional control and survival.

The pedicled latissimus dorsi myocutaneous flap (PLDMF) is not the first-line reconstructive option for most clinicians; however, when treating salvage patients or those with depleted neck vessels, the PLDMF provides a valuable armamentarium. Unlike the pectoralis major myocutaneous flap or the lower island trapezius flap, the PLDMF has greater versatility in soft tissue design and a longer arc of rotation. These advantages are of great importance in managing advanced reconstructive cases.