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Shu-Wei Chen,1–3,* Quan Zhang,1–3,* Zhu-Ming Guo,1–3 Wen-Kuan Chen,1–3 Wei-Wei Liu,1–3 Yan-Feng Chen,1–3 Qiu-Li Li,1–3 Xue-Kui Liu,1–3 Hao Li,1–3 Dian Ou-Yang,1–3 Wei-Chao Chen,1–3 Xiao-Yan Fu,1–3 Xi-Di Wang,1–3 An-Kui Yang,1–3 Jin-Xin Bei,2–4 Ming Song1–3 1Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 2State Key Laboratory of Oncology in South China, 3Collaborative Innovation Center of Cancer Medicine, 4Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China *These authors contributed equally to this work Background: Global data demonstrate minimal improvement in the survival rate for oral cavity cancer (OCC) patients. We wished to know whether or not clinical features and survival rate have changed over time for OCC patients receiving initial treatment and follow-up at a large cancer center in China. Methods: Clinical features and survival data were collected on patients diagnosed during the successive decades of 1960–1969 (n=253), 1970–1979 (n=497), 1980–1989 (n= 659), 1990–1999 (n=793), and 2000–2009 (n=1,160) at the Sun Yat-sen University Cancer Center. Results: Over time, the overall 5-year survival rate for OCC patients was 52.0%. According to tumor localization, this rate was 71.4% for lip cancer, 56.3% for oral tongue cancer, and 42.7% for other parts of the oral cavity. From the 1960s to the 2000s, the 5-year survival rate steadily improved from 47.8% to 55.6% (P

Competing Interests: Conflicts of interest: B.U. is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Incyte, Rapt Therapeutics and Pfizer. He is also a consultant for Arcutis Biotherapeutics, Bristol Myers Squib, Castle Biosciences, Fresenius Kabi, Galderma, Janssen, Lilly, Pfizer, Primus Pharmaceuticals, Sanofi and UCB. The other authors declare no conflicts of interest.

Background: Intratumor heterogeneity is common in cancers, with different cell subtypes supporting each other to become more malignant. Nasopharyngeal carcinoma (NPC), a highly metastatic cancer, shows significant heterogeneity among its cells. This study investigates how NPC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules., Methods: Exosomes were purified and characterized. MicroRNA expression was analyzed via sequencing and qRT-PCR. The effects of miR-30a-5p on migration, invasion, and metastasis were evaluated in vitro and in vivo. Its impact on desmoglein glycoprotein (DSG2) was assessed using dual-luciferase assays and Western blotting. Immunohistochemistry (IHC) and statistical models linked miR-30a-5p/DSG2 levels to patient prognosis., Results: Different NPC cell subtypes transmit metastatic potential via exosomes. High-metastatic cells enhance the migration, invasion, and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p. Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis. miR-30a-5p may promote metastasis by targeting DSG2 and modulating Wnt signaling. Plasma exosomal miR-30a-5p inversely correlates with DSG2 levels, predicting patient outcomes., Conclusion: High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p, which is a valuable prognostic marker assessable via liquid biopsy., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)

High-resolution electron microscopy of nervous systems has enabled the reconstruction of synaptic connectomes. However, we do not know the synaptic sign for each connection (i.e., whether a connection is excitatory or inhibitory), which is implied by the released transmitter. We demonstrate that artificial neural networks can predict transmitter types for presynapses from electron micrographs: a network trained to predict six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) achieves an accuracy of 87% for individual synapses, 94% for neurons, and 91% for known cell types across a D. melanogaster whole brain. We visualize the ultrastructural features used for prediction, discovering subtle but significant differences between transmitter phenotypes. We also analyze transmitter distributions across the brain and find that neurons that develop together largely express only one fast-acting transmitter (acetylcholine, glutamate, or GABA). We hope that our publicly available predictions act as an accelerant for neuroscientific hypothesis generation for the fly., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cranial electrotherapy stimulation (CES) delivers low-intensity electrical currents to the brain to treat anxiety, depression, and pain. Though CES is considered safe and cost-effective, little is known about side effects emerging across different contexts. Our objective was to investigate how varying physical and cognitive demands impact the frequency and intensity of CES vestibular sensations in a sample of healthy young adults. We used a 2 (stimulation: sham, active) × 2 (physical demand: static sway, dynamic sit-to-stand) × 2 (cognitive demand: single-task remain silent, dual-task count backward) repeated measures design. Vestibular sensations were measured with surveys and wearable sensors capturing balance changes. Active stimulation did not influence reported vestibular sensations. Instead, high physical demand predicted more sensation reports. High cognitive demand, but not active stimulation, predicted postural sway unsteadiness. Significant effects of active stimulation on balance were observed only during the dynamic sit-to-stand transitions. In summary, CES induces vestibular sensations only for a specific outcome under certain circumstances. Our findings imply that consumers can safely maximize the benefits of CES while ensuring they are taking steps to minimize any potential side effects by considering their context and circumstances.

Limb salvage is a difficult path for patients to travel as there is no guarantee of the outcome, often the major factor is perfusion. For patients who underwent transmetatarsal amputation (TMA), success rate is crucial as the next option is most likely a major amputation. We performed a 10 years (2010-2020) retrospective review of patients that underwent a TMA and had an angiogram or computed tomography angiography (CTA) perioperatively at the Dallas VA Medical Center. Failure after TMA was defined as a patient requiring a proximal amputation within 1 year. There were 125 TMAs performed between 2010 and 2020 at the institution. Forty-four (35.2%) patients had an angiogram/CTA peri-operative and met the inclusion criteria. Seventeen subjects (38.6%) had a higher level of amputation. Of the 17 failures, 2 (11.8%) patients had no patent vessel runoff to the foot, 9 (52.9%) had one vessel, 4 (23.5%) had two vessels, and 2 (11.8%) had three vessels runoff. One vessel runoff to the foot yielded a high rate of poor outcomes (56.3%) defined as a higher level of amputation. Two or more vessels runoff to the foot had over 75% success of limb salvage with a TMA., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: To explore the therapeutic effects of transoral robotic surgery (TORS) and traditional surgical modes in oropharyngeal squamous cell carcinoma (OPSCC). Methods: The clinicopathological data of patients with oropharyngeal squamous cell carcinoma treated at Sun Yat-sen University Cancer Center from 2010 to 2018 were retrospectively analyzed. 135 cases were treated with traditional surgery (non-TORS group), while 52 cases were treated with TORS (TORS group). The prognosis of the two groups of patients were analyzed by Kaplan-Meier method and Log rank test, the influencing factors were analyzed by Cox regression model. Results: The 2-year overall survival (OS, 94.2%) and 2-year progression-free survival (PFS, 93.8%) of patients in the TORS group were better than those in the non-TORS group (71.4% and 71.4%, respectively, P <0.05). The 2-year OS (93.3%) and 2-year PFS (92.8%) of TORS group patients in T1-2 stage were better than those of non-TORS group (73.1% and 72.8%, respectively, P <0.05). The 2-year OS (95.8%) and 2-year PFS (95.2%) of patients with stage Ⅰ to Ⅱ in the TORS group were not significantly different from those in the non-TORS group (84.1% and 83.9%, respectively, P >0.05). The 2-year OS (92.9%) and 2-year PFS rate (92.7%) of patients with stage Ⅲ to Ⅳ in the TORS group were better than those in the non-TORS group (64.7% and 63.9%, respectively, P <0.05). The 2-year OS (94.4%) of HPV-positive patients in the TORS group was not significantly different from that in the non-TORS group (83.3%, P =0.222). The 2-year OS of HPV-negative patients in the TORS group (94.1%) was significantly different from that in the non-TORS group (43.7%, P <0.001). HPV status was an independent prognostic factor ( P =0.008). Conclusions: TORS has a better prognosis in the treatment of oropharyngeal squamous cell carcinoma compared with the traditional treatment methods. The patients with T1-T2 can achieve better survival benefits after TORS treatment. The HPV-positive OPSCC patients has a better prognosis than that of HPV-negative OPSCC patients, and regardless of HPV status, OPSCC patients in the TORS group could obtain a better survival prognosis.

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.

Objective: To evaluate the therapeutic and prognostic outcomes of transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OSCC). Methods: A retrospective study of 99 OSCC patients treated with TORS in Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center between April 2017 and May 2021 was conducted. There were 84 males and 15 females, with an age range of 35-85 years. Patients' clinical characteristics, including clinical staging, HPV infection status, perioperative management and postoperative adjuvant treatment, were recorded. The overall survival (OS) and progression-free survival (PFS) were analyzed. The survival outcomes were analyzed with Kaplan-Meier method and Log-rank test. Results: The hospital stay of OSCC patients with TORS was (5.3±2.9) days and the average time of postoperative nasal feeding tube indwelling was (15.2±10.8) days. Among the 99 patients, 21 (21.2%) received tracheotomy and the average time of tracheotomy tube indwelling was (11.9±11.4) days. The two-year OS and PFS in patients with follow-up over two years were 94.0% and 87.7%, respectively and the three-year OS and PFS of patients with follow-up over three years were 94.0% and 78.9%, respectively. The two-year OS and PFS were respectively 97.4% and 88.9%, for patients with stages I-II and 86.8% and 88.9% for patients with stages III-IV. HPV-negative and HPV-positive patients had respectively two-year OS (100.0% vs. 91.5%) and PFS (88.9% vs. 87.2%). There was no significantly statistical difference in survival between patients with and without adjuvant radiotherapy after TORS (82.6% vs . 90.5%, HR =0.52, 95% CI : 0.12-2.23, P =0.400). Conclusions: TORS is more suitable for the treatment of patients with early (Ⅰ-Ⅱ) or HPV-positive oropharyngeal squamous cell carcinoma, and the recovery after TORS treatment is good.

Objectives: To compare the efficiacy of retro-auricular single-site endoscopic thyroidectomy (RASSET) and that of transoral endoscopic thyroidectomy vestibular approach (TOETVA). Methods: In Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 10 patients underwent RASSET from June 2021 to August 2021, and 21 patients underwent TOETVA from January 2016 to August 2021. All the 21 patients' clinical data was analyzed retrospectively. There were 2 males and 8 females in the RASSET group, aging (48.2±13.9) years (range: 28 to 67 years). There were 5 males and 16 females in the TOETVA group, aging (31.3±8.2) years (range: 21 to 49 years). All patients underwent thyroid lobectomy. A 3 cm in length incision was cut on single auricula posterior sulci to creat the approach in the RASSET group. Then a Trocar made with of a glove was inserted. Retaining the omohyoid, the sternocleidomastoid muscle and anterior cervical muscle were pulled apart, exposing a single lobe of the thyroid gland and lymphatic tissue of zone Ⅵ, for en-bloc resection. The clinical data of the two groups were collected and analyzed by t test, Mann-Whitney U test, Fisher exact test or χ 2 test. Clinical data and postoperative efficacy indexes such as operation time, postoperative C reactive protein level, and postoperative complications were recorded. Results: Compared with the TOETVA group, the operation time was longer in the RASSET group ((256.8±77.0) minutes vs. (201.2±54.9) minutes, t =2.31, P= 0.028), and increase of postoperative C reaction protein (24 hours postoperative vs. preoperative) was lower in the RASSET group (8.58(13.24) mg/L vs. 46.24(48.88) mg/L, Z =-4.311, P <0.01). But there was no significant difference between the RASSET group and TOETVA group in the number of lymph nodes dissection (2(5) vs. 2(3), Z =-0.326, P =0.759). Besides, there were no complications in the RASSET group. Conclusion: Retro-auricular single-site endoscopic thyroid loectomy is easy to achieve the en-bloc resection of tumors with a well-concealed scar and less traumatic dissection.

Objective: To evaluate the safety, efficacy and feasibility of transoral robotic surgery (TORS) for parapharyngeal space (PPS) neoplasms. Methods: We collected data from 7 patients with PPS neoplasm who received TORS in Sun Yat-sen University Cancer Center between May 2017 and November 2020, and patients' clinical and pathological characteristics were analysed. There were 2 men and 5 women with age ranged from 35 to 76 years. Among them, 2 patients underwent secondary surgery, 2 patients required combined transcervical approach to complete surgery, and 1 patient was suspected of ipsilateral cervical lymph node metastasis and scheduled for diagnostic TORS. The preoperative tumor size, operation time, intraoperative blood loss, postoperative bleeding, dyspnea, neurological impairment, feeding time and postoperative hospital stay were analyzed. SPSS 24.0 was used to analyze the data. Results: TORS was performed successfully with complete removal of tumors in all 7 cases. Among 6 patients with curative TORS, 5 patients received TORS with postoperative diagnoses of neurogenic tumors and 1 patient underwent TORS combined transcervical approach with postoperative disgnosis of recurrent pleomorphic adenoma; no intraoperative tumor rupture occurred; the intraoperative blood loss was 20-200 ml with a median of 40 ml; the operation time was 65.0-238.0 min with a median of 77.5 min; the oral feeding time was 3-6 days with a median of 3 days; and the postoperative hospital stay was 4.2±1.6 days. One patient presented with neck swelling 3 days after surgery, but this symptom relieved 3 days later after treatments with antibiotic, hemostasis and detumescence. One patient received diagnostic TORS, as intraoperative pathology indicating a recurrent pleomorphic adenoma, then the neoplasm got completely resected through transcervical-transparotid approach. None of 7 patients manifested with airway obstruction, bleeding or nerve injury symptoms after operation. All patients were followed for 2 to 44 months, no local recurrence or distant metastasis was found. Conclusions: TORS is a safe, effective and feasible treatment for selected PPS neoplasms, with less cosmetic impact, less trauma and blood loss, few postoperative complications, enhanced postoperative recovery and short hospital stay.

Immunologic checkpoint blockade has been proven effective in a variety of malignancies. However, high rates of resistance have substantially hindered its clinical use. Understanding the underlying mechanisms may lead to new strategies for improving therapeutic efficacy. Although a number of signaling pathways have been shown to be associated with tumor cell-mediated resistance to immunotherapy, T cell-intrinsic resistant mechanisms remain elusive. Here, we demonstrated that diacylglycerol kinase alpha (Dgka) mediated T-cell dysfunction during anti-PD-1 therapy by exacerbating the exhaustion of reinvigorated tumor-specific T cells. Pharmacologic ablation of Dgka postponed T-cell exhaustion and delayed development of resistance to PD-1 blockade. Dgka inhibition also enhanced the efficacy of anti-PD-1 therapy. We further found that the expression of DGKA in cancer cells promoted tumor growth via the AKT signaling pathway, suggesting that DGKA might be a target in tumor cells as well. Together, these findings unveiled a molecular pathway mediating resistance to PD-1 blockade and provide a potential therapeutic strategy with combination immunotherapy., (©2021 American Association for Cancer Research.)

There is a compelling need to identify novel genetic variants for papillary thyroid cancer (PTC) susceptibility. The Cancer Genome Atlas (TCGA) data showed associations between SPP1 and SPARC mRNA overexpression and aggressive behaviors of PTC, which prompted us to assess potential associations between genetic variants in these genes and PTC risk. Three highly linked SPARC loci (rs1054204, rs3210714, and rs3549) contributed to reduced PTC risk under a codominant model (odds ratio [OR], 0.79-0.80). Variant CAG alleles at these loci significantly enhanced SPARC transcription activation upon cotransfection with miR-29b and miR-495 when compared to the common alleles GGC (all P < 0.05). The three SPARC polymorphisms interacted with SPP1 rs4754, with elevated joint ORs of 2.43, 2.52, and 2.52, respectively. Additionally, interaction between SPP1 rs2358744 and SPARC rs2304052 was observed. Our study revealed associations between SPP1 and SPARC polymorphisms that, individually or in combination, are involved in PTC susceptibility., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Few reports from China provide confirmed evidence of the effectiveness of the larynx preservation strategy compared with surgery on the treatment of laryngeal and hypopharyngeal cancers. This study assessed the clinical outcomes of patients with locally advanced laryngeal and hypopharyngeal cancers treated with larynx preservation and determined the optimal larynx preservation procedure., Methods: Data of 1,494 patients treated with total laryngectomy or larynx preservation between 2006 and 2014 were retrieved from the database of Sun-Yat Sen University Cancer Center in Guangzhou, China, and 366 eligible patients were selected for final analysis. The clinical outcomes of 228 patients received total laryngectomy and 138 patients received larynx preservation treatments, which comprises induction followed by radiotherapy and concurrent radio-chemotherapy, were compared., Results: There was no statistical difference in the 3-, 5-, and 10-year PFS and OS in patients received larynx preservation compared with patients treated with laryngectomy. With respect to T stage, a better overall OS in T2-stage disease (P = 0.036) but poorer PFS (P = 0.005) in T3-stage disease was observed in the larynx preservation group compared with the surgery group in Univariate analysis. T3-stage disease had poorer PFS in multivariable analysis (P = 0.022). With larynx preservation intent, induction chemotherapy followed by radiotherapy showed no advantage in the control of disease progression and survival compared with concurrent chemoradiotherapy. The patient subpopulations who received efficacy assessment after induction chemotherapy exhibited significantly longer PFS and OS compared with those without efficacy assessment., Conclusions: This is the largest sample size study on larynx preservation treatment for laryngeal and hypopharyngeal cancers in China. Our results indicated that larynx preservation treatments did not jeopardize the survival of patients with advanced resectable laryngeal or hypopharyngeal cancers. Efficacy assessment should be emphasized in induction chemotherapy., (Copyright © 2020 Su, He, Ye, Zhou, Liu, Yang, Long, Tang, Ma, Xu, Chen, He and Yang.)

Background: Insight into the neural basis of hedonic processing has come from studies of food palatability in rodents. Pharmacological manipulations of the nucleus accumbens shell (NAcSh) have repeatedly been demonstrated to increase hedonic taste reactivity, yet the contribution of specific NAcSh circuit components is unknown., Methods: Bidirectional optogenetic manipulations were targeted to the principal NAcSh projection neurons and afferent pathways in mice during free feeding assays. Number of licks per bout of consumption was used as a measure of food palatability as it was confirmed to track sucrose concentration and subjective flavor preferences., Results: Photoinhibition of NAcSh neurons, whether general or cell-type specific, was found to alter consumption without affecting its hedonic impact. Among the principal excitatory afferent pathways, we showed that ventral hippocampal (vHipp) input alone enhances palatability upon low-frequency photostimulation time-locked to consumption. This enhancement in palatability was independent of opioid signaling and not recapitulated by NAcSh or dopamine neuron photostimulation. We further demonstrated that vHipp input photostimulation is sufficient to condition a flavor preference, while its inhibition impedes sucrose-driven flavor preference conditioning., Conclusions: These results demonstrate a novel contribution of vHipp-NAcSh pathway activity to palatability that may relate to its innervation of a particular region or neuronal ensemble in the NAcSh. These findings are consistent with the evidence that vHipp-NAcSh activity is relevant to the pathophysiology of anhedonia and depression as well as the increasing appreciation of hippocampal involvement in people's food pleasantness ratings, hunger, and weight., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

The nucleus accumbens (NAc) contributes to behavioral inhibition and compulsions, but circuit mechanisms are unclear. Recent evidence suggests that amygdala and thalamic inputs exert opposing control over behavior, much like direct and indirect pathway output neurons. Accordingly, opponent processes between these NAc inputs or cell types may underlie efficient reward seeking. We assess the contributions of these circuit elements to mouse operant behavior during recurring conditions when reward is and is not available. Although direct pathway stimulation is rewarding and indirect pathway stimulation aversive, the activity of both cell types is elevated during periods of behavioral suppression, and the inhibition of either cell-type selectively increases unproductive reward seeking. Amygdala and thalamic inputs are also necessary for behavioral suppression, even though they both support self-stimulation and innervate different NAc subregions. These data suggest that efficient reward seeking relies on complementary activity across NAc cell types and inputs rather than opponent processes between them., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRs) play important roles in tumor progression. miR-936 has been reported to suppress cell invasion and proliferation of glioma and non-small cell lung cancer. Nevertheless, the function of miR-936 in laryngeal squamous cell carcinoma (LSCC) remains undiscovered. Hence, our study was to investigate the role of miR-936 in LSCC. In our present research, we have testified that miR-936 was substantially downregulated in LSCC tissues compared with adjacent normal tissues. Furthermore, miR-936 could inhibit proliferation, migration and invasion, and improve the sensitivity to doxorubicin and cisplatin of LSCC cells. Additionally, luciferase reporter assays were performed to confirm that GPR78 was a novel target of miR-936, and the protein expression of GPR78 was obviously inhibited by miR-936 in LSCC cells. In summary, our study indicates that the miR-936/GPR78 axis could be both a diagnostic marker and a therapeutic target for LSCC., (Copyright © 2020 Lin, Liu, Li, Wang, Yang, Di, Jiang, Yang, Huang, Yuan, Xing, Wei, Li, Shi and Ye.)

The burgeoning functions of many microRNAs (miRs) have been well study in cancer. However, the level and function of miR-1205 in laryngeal squamous cell cancer remains unknown. In the current research, we validated that miR-1205 was notably downregulated in human laryngeal squamous cell carcinoma (LSCC) samples in comparison with tissues adjacent to LSCC, and correlated with T stage, lymph node metastasis, and clinical stage. Using Kaplan-Meier analysis indicates that high expression of miR-1205 has a favorable prognosis for patients with LSCC. Functional assays show that enforced miR-1205 expression attenuates the migration, growth, and invasion of LSCC cells. And E2F1 is verified to be a target of miR-1205, while E2F1 binds to miR-1205 promoter and transcriptionally inhibits miR-1205 expression. Overexpression of E2F1 reverses the inhibitory impacts of miR-1205 on LSCC cells in part. Importantly, E2F1 is abnormally increased in LSCC tissues, and its protein levels were inversely relevant to miR-1205 expression. High E2F1 protein level is in connection with clinical stage, T stage, lymph node metastasis, and poor prognosis. Consequently, reciprocal regulation of miR-1205 and E2F1 plays a crucial role in the progression of LSCC, suggesting a new miR-1205/E2F1-based clinical application for patients of LSCC.

Objective: To investigate the role of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and P16 in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: A total of 95 paraffin-embedded samples of tumorous tissue of HNSCC were collected. Expression levels of PD-1, PD-L1, and P16 were determined by immunohistochemistry., Results: A significantly higher proportion of PD-1 among patients infected with the human papillomavirus was found. PD-L1 expression is closely associated with the primary site of the tumor, postoperative recurrence, survival, PD-1 expression and P16 expression. Univariable analysis indicated that T stage, N stage, tumor node metastasis stage, tumor differentiation, and PD-L1 expression were all shown to be prognostic variables for overall survival in patients with HNSCC. In the multivariate analysis, only N stage ( P = 0.010) and PD-L1 expression ( P = 0.001) were found to be independent prognostic variables for overall survival. In addition, for disease recurrence, multivariate analysis showed that only PD-L1 expression was the associated independent risk factor. For the patients with negative PD-L1 expression, Kaplan-Meier analysis revealed that they had significantly worse outcomes in terms of overall survival ( P = 0.001). Similarly, compared with the patients with positive PD-L1 expression, those with negative PD-L1 expression had a higher probability of recurrence ( P = 0.026)., Conclusions: The expression of PD-L1, PD-1, and P16 in HNSCC is significantly correlated. Human papillomavirus infection (P16 positive) is negatively related to postoperative recurrence. HNSCC patients with positive PD-L1/PD-1 expression tend to have better overall survival outcomes and lower probability of recurrence, providing more evidence for the PD-l-targeted immunotherapy of HNSCC.

Cue-evoked midbrain dopamine (DA) neuron activity reflects expected value, but its influence on reward assessment is unclear. In mice performing a trial-based operant task, we test if bidirectional manipulations of cue or operant-associated DA neuron activity drive learning as a result of under- or overexpectation of reward value. We target optogenetic manipulations to different components of forced trials, when only one lever is presented, and assess lever biases on choice trials in the absence of photomanipulation. Although lever biases are demonstrated to be flexible and sensitive to changes in expected value, augmentation of cue or operant-associated DA signaling does not significantly alter choice behavior, and blunting DA signaling during any component of the forced trials reduces choice trial responses on the associated lever. These data suggest cue-evoked DA helps maintain cue-value associations but does not encode expected value as to set the benchmark against which received reward is judged., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

To estimate the value of FSCN1 in evaluating the prognosis and guiding the targeted therapy for patients with tongue squamous cell carcinoma (TSCC). Using the Oncomine database, we found some genes especially FSCN1 differentially expressed between TSCC samples and tongue normal samples. So we compared FSCN1 expression between TSCC and normal cell lines and knocked down FSCN1 in TSCC cells to observe its influence on the viability and trans-migration in vitro and tumor growth in vivo. Then we measured FSCN1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between FSCN1 expression and clinical pathological factors and prognosis in TSCC patients. We found that FSCN1 is expressed higher in TSCC cells than in normal cells. Knockdown of FSCN1 reduced TSCC cell viability and trans-migration in vitro and impaired tumor growth in vivo. FSCN1 also expressed higher in human TSCC than in ANT. In addition, FSCN1 expression was related to N classification, clinical stage and relapse. TSCC patients with over-expression of FSCN1 had worse prognosis. In conclusion, over-expression of FSCN1 indicates worse prognosis for patients with TSCC and FSCN1 may be a potential prognostic biomarker and therapeutic target in TSCC.

Background: Xenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized., Methods: Real-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay., Results: Herein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens., Conclusions: These findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.

Hybrid approaches combining gene‑ and cell‑based therapies to make biological pacemakers are a promising therapeutic avenue for bradyarrhythmia. The present study aimed to direct adipose tissue‑derived stem cells (ADSCs) to differentiate specifically into cardiac pacemaker cells by overexpressing a single transcription factor, insulin gene enhancer binding protein 1 (ISL‑1). In the present study, the ADSCs were transfected with ISL‑1 or mCherry fluorescent protein lentiviral vectors and co‑cultured with neonatal rat ventricular cardiomyocytes (NRVMs) in vitro for 5‑7 days. The feasibility of regulating the differentiation of ADSCs into pacemaker‑like cells by overexpressing ISL‑1 was evaluated by observation of cell morphology and beating rate, reverse transcription‑quantitative polymerase chain reaction analysis, western blotting, immunofluorescence and analysis of electrophysiological activity. In conclusion, these data indicated that the overexpression of ISL‑1 in ADSCs may enhance the pacemaker phenotype and automaticity in vitro, features which were significantly increased following co‑culture induction.

Objective: To compare survival effects of comprehensive neck dissection (CND) and selective neck dissection (SND) for patients with nasopharyngeal carcinoma (NPC) with only regional failure., Methods: A total of 294 recurrent T0N1-3M0 NPC patients who underwent neck dissection in Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China, between January 1984 and February 2014, were enrolled in the survival and interaction analyses. Using propensity scores to adjust for potential prognostic factors, an additional well-balanced cohort of 210 patients was constructed by matching each patient who received SND with one patient who underwent CND (1:1); the differences were then compared between SND and CND in terms of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS)., Results: Both univariate and multivariate analyses showed that SND was not inferior to CND (P > 0.05) but demonstrated that extracapsular spread (ECS) (hazard ratio [HR] 3.49, 95% confidence interval [CI] 2.30-5.29, P < 0.001), recurrent N stage (rN stage) (HR 1.96, 95% CI 1.29-2.97, P = 0.002), and positive margins (HR 3.67, 95% CI 2.40-5.62, P < 0.001) were independent poor prognostic factors for OS. The interaction effects between the dissection style and each independent factor were not significant for OS, LRFS, RRFS, or DMFS (P > 0.05). Furthermore, no survival differences were found between SND and CND in the case-matched cohort in terms of OS, LRFS, RRFS, or DMFS (P = 0.550, 0.930, 0.214, and 0.146, respectively)., Conclusion: With a similar radical dissection extent around the tumor rather than dissection of extensive lymph region distal to the lesion, SND is not inferior to CND for patients with NPC with only cervical failure. ECS, rN stage, and positive margins were adverse independent prognostic factors for patients with NPC., Level of Evidence: 4 Laryngoscope, 129:387-395, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

This study aimed to evaluate the association of potential functional tagging single nucleotide polymorphisms (tagSNPs) in BRAF and TSHR with papillary thyroid cancer (PTC). Two tagSNPs (rs6464149 and rs7810757) in BRAF and six tagSNPs (rs17630128, rs2075179, rs7144481, rs2371462, rs2268477, and rs2288496) in TSHR were genotyped in 300 cases of PTC and 252 healthy controls. There was no difference in the genotype frequencies of BRAF and TSHR between PTC patients and control subjects, suggesting no contribution of BRAF or TSHR polymorphisms to the susceptibility to PTC. We observed that a tagSNP located in the 3' untranslated region of TSHR, rs2288496, could affect the incidence of lymph node metastasis (LNM). The variant TC and TC + CC genotypes conferred an increased risk of LNM (for TC vs. TT: odds ratio (OR) = 2.01, 95% confidence interval (CI): 1.07-3.77; P= 0.030; for TC + CC vs. TT: OR = 1.87, 95% CI: 1.04-3.39, P= 0.038). Moreover, subjects carrying variant genotypes had higher TSH levels and lower thyroxine (T4) and Anti-TG levels compared with those in subjects carrying common genotypes. Our findings showed that PTC patients carrying the TSHR rs2288496 TC and CC variants were associated with higher TSH level and lower T4 and Anti-TG levels and were prone to developing LNM. To confirm these results, additional studies and functional experiments, especially in other ethnic populations, are needed.

WEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in LSCC tissues compared with adjacent normal tissues. Importantly, overexpression of WEE1 was correlated with T stages, lymph node metastasis, clinical stages and poor prognosis of LSCC patients. Furthermore, inhibition of WEE1 by MK-1775 induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular reactive oxygen species (ROS) levels in LSCC cells. Pretreatment with ROS scavenger N -acetyl-L-cysteine could reverse MK-1775-induced ROS accumulation and cell apoptosis in LSCC cells. MK-1775 also inhibited the growth of LSCC xenografts in nude mice. Altogether, these findings suggest that WEE1 is a potential therapeutic target in LSCC, and inhibition of WEE1 is the prospective strategy for LSCC therapy.

Reward-seeking behavior is regulated by a diverse collection of inputs to the nucleus accumbens (NAc). The information encoded in each excitatory afferent to the NAc is unknown, in part because it is unclear when these pathways are active in relation to behavior. Here we compare the activity profiles of amygdala, hippocampal, and thalamic inputs to the NAc shell in mice performing a cued reward-seeking task using GCaMP-based fiber photometry. We find that the rostral and caudal ends of the NAc shell are innervated by distinct but intermingled populations of forebrain neurons that exhibit divergent feeding-related activity. In the rostral NAc shell, a coordinated network-wide reduction in excitatory drive correlates with feeding, and reduced input from individual pathways is sufficient to promote it. Overall, the data suggest that pathway-specific input activity at a population level may vary more across the NAc than between pathways., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Clinically, we have observed that some oral cancer patients have a history of radiotherapy for head and neck cancer; we have named this condition radiotherapy-associated cancer (RAC). Gingival cancer, which is usually juxtaposed with other oral cancer subtypes, is seldom reported individually, and there are few reports on the association between the incidence of oral cancer and history of radiation therapy. Therefore, this study aimed to elucidate the clinicopathological features and prognosis of second primary gingival squamous cell carcinoma after head and neck radiotherapy., Materials and Methods: The data collected included 450 patients diagnosed with gingival squamous cell carcinoma from 1964 to 2012 at Sun Yat-sen University Cancer, among whom 52 patients had a history of radiotherapy for head and neck cancer. We retrospectively analysed the differences in the clinicopathological characteristics and prognosis between sporadic gingival squamous cell carcinoma and radiation-associated gingival carcinoma, with an emphasis on gingival carcinoma., Results: Sporadic gingival squamous cell carcinoma is less likely to have more advanced T stage, and the second primary tumour is more likely to be located in the molar area of the maxillary gingiva than in the mandibular gingiva (75.6% vs 24.4%, P < 0.05). The 5-year overall survival of patients with second primary gingival carcinoma was influenced by age distribution, T classification, N classification, clinical TNM stage, histological grade and radiation history in head and neck. Mandibular gingival carcinoma was more likely to have an increased neck lymph node metastasis than maxillary gingival carcinoma (P = 0.001), but there was no significant difference in 5-year overall survival between these two groups (P = 0.828). The main therapy for gingiva carcinoma is surgery or comprehensive treatment based on surgery., Conclusions: Second primary gingival squamous cell carcinoma after radiotherapy demonstrated particular clinicopathologic features, such as prominent sites and TNM stage; and there was statistically significant difference in 5-year overall survival and prognosis between second primary gingival carcinoma after radiotherapy and sporadic gingival carcinoma., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: RET / PTC gene rearrangement can lead to aberrant activation of tyrosine kinase receptors, which is a common mutation in papillary thyroid carcinoma (PTC). This study focuses on the association of RET / PTC rearrangements with PTC clinical factors. Methods: From January 2011 to December 2013, a total of 114 patients with PTC were enrolled in this study. Clinicopathological parameters, lifestyle, and thyroid hormone levels were collected. RET / PTC rearrangements were detected by TaqMan PCR and verified by Sanger sequencing.Data were analyzed with SPSS software, including chi-square test, Fisher ' s exact test, Mann - Whitney U test, Student ' s t -test, and Logistic regression. Results: RET / PTC rearrangements were not found in all paracancerous normal thyroid tissues, and were detected in 23.68% (27/114) of PTC. Further analysis revealed no correlation between RET / PTC rearrangement and thyroid function, clinicopathologic parameters, and lifestyle in the total PTC group or in the subgroup of patients with concomitant diseases (including Hashimoto's thyroiditis and nodular goiter). But in the subgroup of PTC without concomitant disease, RET / PTC rearrangement was associated with tumor multifocal ( P =0.018), and RET / PTC -positive PTC patients had an increased risk of tumor multifocal ( OR =5.57, 95% CI 1.39-22.33). It was also found that RET / PTC rearrangement was associated with an abnormal increase in TSH level of one month after surgery ( P = 0.037). Conclusion: Nodular goiter and Hashimoto 's thyroiditis may be a confounding factor in PTC. RET / PTC rearrangement may play an important role in the occurrence of thyroid carcinoma multifocal after exclusion of this confounding factor.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Introduction: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the most aggressive human cancers. The optimal multimodal therapy policy of ATC is still debated, and a standardized treatment strategy remains to be established. This study aimed to evaluate the management aspect and prognosis of ATC., Materials and Methods: The data were analyzed retrospectively for 50 patients with ATC to evaluate the clinical characters, management and factors influencing survival. Survival analysis was performed by Kaplan-Merier method and log-rank test, and multivariate analysis was performed using Cox proportional hazard model., Results: The 1-year and 2-year overall survival rates (OS) were 48.0% and 26.0% respectively in all patients, with the 2-year OS of 40.0% and 31.0% and 6.3% for stage IVA, IVB and IVC respectively (P <0.05). In stage IVA and IVB patients, combined surgery with radiotherapy improved overall survival, and the 2-year OS were 50.0% and 35.7% respectively in the group with combined surgery with radiotherapy and the group with surgery with only (P <0.05). Postoperative radiotherapy improved local control rate in stage IVA and IVB patients (P <0.05). However, surgery, radiotherapy or chemotherapy could not improve the survival of stage IVC patients. Multivariate analysis showed that distant metastases, surgery, radiotherapy and tumor residue could predict the prognosis., Conclusion: Combined surgery and radiotherapy could improve overall survival in stage IVA and IVB patients. Patients with ATC have a bad prognosis. Distant metastases, surgery, radiotherapy and tumor residue are the most important factors affecting the prognosis., Competing Interests: The authors have declared that no competing interests exist.

Objective: Although endocrine therapy of papillary thyroid carcinoma (PTC) by inhibiting thyroid-stimulating hormone (TSH) has been used for many years, its mechanism of action is not clear. This study aimed to explore the expression and role of TSH receptor (TSHR) in PTC, to provide a theoretical basis for optimization of endocrine treatment options in PTC., Patients and Methods: Expression of TSHR was tested by immunohistochemistry of tissues from 150 cases of PTC and 21 normal thyroid tissues. Survival analysis was performed by Kaplan-Meier and log-rank analyses, and multivariate analysis was done using a Cox model. The regulatory effects of the TSH-TSHR signal transduction pathway on differentiated thyroid carcinoma cells were explored in vitro., Results: The positive expression rate of TSHR in PTC was 68% (102/150). TSHR expression was an independent factor affecting the prognosis of PTC patients aged > 45 years (p = 0.006), and TSHR might have a role in decreasing distant metastasis (p = 0.024). In vitro experiments showed that up-regulation of TSHR promoted apoptosis of thyroid cancer cells and inhibited metastasis significantly. There was no significant regulatory effect of the TSH-TSHR signal transduction pathway on the proliferation of thyroid carcinoma cells., Conclusions: TSHR expression is an independent factor that affects the prognosis of PTC patients, and might decrease distant metastasis in patient aged > 45 years. Up-regulation of TSHR could inhibit metastasis and promote apoptosis in PTC cells.

Anaplastic thyroid cancer (ATC), an undifferentiated subtype of thyroid cancer, is one of the most malignant endocrine cancer with low survival rate, and resistant to chemotherapy and radiation therapy. Here we found that UHRF1 was highly expressed in human ATC compared with normal tissue and papillary thyroid cancer (PTC). Knockdown of UHRF1 inhibited proliferation of ATC in vitro and in vivo . Consistently, overexpression of UHRF1 promoted the proliferation of thyroid cancer cells. Moreover, UHRF1 suppression induced differentiation of three-dimensional (3D) cultured ATC cells and down-regulated the expression of dedifferentiation marker (CD97). The stem cell markers (Sox2, Oct4 and Nanog) were suppressed simultaneously. In addition, UHRF1 knockdown reduced the transcription of cytokines (IL-8, TGF-α and TNF-α), which might relieve the inflammatory reaction in ATC patients. This study demonstrated a role of UHRF1 in ATC proliferation, dedifferentiation and inflammatory reaction, presenting UHRF1 as a potential target in ATC therapy., Competing Interests: CONFLICTS OF INTEREST The authors declare that there is no potential conflicts of interest.

Background: Oral cancer is a common type of head and neck cancers. Knowing its epidemiologic characteristics is crucial to preventing, diagnosing, and treating this cancer. This study aimed to explore the epidemiologic characteristics of oral cancer in South China., Methods: We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013. We compared the age of onset, sex ratio, pathologic type, and primary tumor location among three subcultural areas (Guangfu, Hakka, and Chaoshan) and between an economically developed region and a less-developed one in Guangdong., Results: Overall, oral cancer had a male-to-female ratio of approximately 2:1, and this ratio decreased over time. Oral cancer occurred mostly in patients of 45-64 years old (54.5%), and the percentage of older patients gradually increased over time. The most common tumor location was the tongue. Squamous cell carcinoma was the predominant pathologic type. The percentage of blood type O in oral cancer patients was lower than that in the healthy population. The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas, whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan. The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region., Conclusion: The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.

Pinato prognostic nutritional index (PNI) adequately predicts long-term outcomes of various malignancies. However, its value in predicting outcomes in laryngeal squamous cell carcinoma (LSCC) is unknown. All patients newly diagnosed with LSCC presenting to the Department of Head and Neck Oncology at Sun Yat-sen University Cancer Center between January 1, 1990 and July 31, 2010 were eligible. The PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count/L. The Cutoff Finder software program was used to classify the patients into 3 groups for which the PNI score was at least 70% sensitive, at least 70% specific, or equivocal. Cancer-specific survival was estimated using the Kaplan-Meier method, and predictors were assessed with Cox regression analysis. Median time between surgery and PNI administration for the 975 eligible patients was 83 months. Index score groups were significantly associated with age, T stage, TNM stage, and type of surgery. Five-year CSS and OS were 57.3% and 56.6% in patients with PNI scores below 48.65 (low-probability of survival), 72.8% and 71.3% with scores between 48.65 and 56.93 (moderate-probability of survival), and 77.6% and 75.3% with scores above 56.93 (high-probability of survival); 10-year CSS and OS were 44.2% and 42.7%, 61.6% and 55.6%, 68.3% and 63.5%, respectively. The PNI score groups significantly predicted CSS and OS (P < 0.001). The PNI is an inexpensive and readily available score that predicted survival in patients with LSCC after curative laryngectomy.

Objective: Patients with head and neck cancer often suffer from malnutrition. This study aims to investigate the influence of body mass index (BMI) on the prognosis of laryngeal squamous cell carcinoma (LSCC)., Methods: A total of 473 patients with LSCC initially treated at Sun Yat-sen University Cancer Center between January 2005 and July 2009 were retrospectively reviewed. Survival analysis was performed by the Kaplan-Meier method and Cox regression model., Results: Low BMI before treatment was significantly associated with poor overall survival in patients with LSCC (P<0.001). BMI was an independent prognostic factor for patients with LSCC., Conclusion: Leanness before treatment was associated with poor prognosis in patients with LSCC. Good nutritional status is favorable to improve survival in patients with LSCC.

Introduction: Metabolic syndrome (MS) is associated with several cancers, but it is not clear whether MS affects the prognosis of tongue squamous cell carcinoma (TSCC). This study aimed to evaluate the prognostic value of MS in TSCC., Methods: Clinical data from 252 patients with TSCC who were initially treated at the Sun Yat-sen University Cancer Center between April 1998 and June 2011 were collected, and the associations between MS and clinicopathologic factors were retrospectively analyzed. Prognostic outcomes were examined by Kaplan-Meier analysis and Cox regression analysis., Results: Of the 252 patients, 48 were diagnosed with MS. MS was associated with early N category in TSCC (P < 0.001). The patients with MS showed longer survival than those without MS (P = 0.028). MS was an independent prognostic factor for patients with TSCC., Conclusions: MS is associated with early N category in TSCC. It is an independent prognostic factor for better survival in patients with TSCC.

Toxicological assessments of human red blood cells (RBCs) are important in human health because RBCs are the most abundant cell type in our body. Erythrotoxicology testing guidelines using hemolysis have been established as a standard (e.g. by the ASTM International). However, many xenobiotics promote eryptosis (apoptosis in human RBCs) without causing hemolysis. Based on the major features of eryptosis, i.e. cell shrinkage and translocation of phosphatidylserine (PS) to the outer lipid bilayer of the plasma membrane, we report here a novel approach utilizing the quantitative tunable resistive pulse sensing (TRPS) technology, a widely adopted technique for characterizing nanoparticles in the field of nanotechnology, to measure the degree of eryptosis in a non-optical manner. With the TRPS system, we were able to determine PS externalization with microbeads functionalized with annexin-V for PS binding, cell swelling and shrinkage in physiological buffers (cell volume: 86 ± 12 fL) and solutions of different osmolarities with or without apoptotic trigger. After setting these standards, we then evaluated the toxicity of Polyphyllin D (PD), a potential anti-cancer drug that kills more liver cancer cells with multi-drug resistance, in erythrocytes to prove our concept. Data revealed that PD induced PS externalization and shrinkage in RBCs in a dose-dependent manner. Moreover, another feature of eryptosis, as small as 5 fL, was detected thus showing the PD-induced erythrotoxicity in human cells. Taken together, our results indicate that our approach using annexin-V-beads and TRPS is simple, safe and convenient, using only a small volume (35 μL) to evaluate the erythrotoxicity of xenobiotics.

Background: The purpose of this study was to evaluate the outcome in sinonasal mucosal melanoma (SMM)., Methods: A retrospective analysis of clinicopathological data from January 1976 to December 2005 was performed. Survival curve, univariate, and multivariate analyses were undertaken., Results: Sixty-eight patients with SMM were enrolled; 3 patients refused treatment. The 3-year and 5-year overall survival (OS) rates in the remaining 65 cases of SMM were 36.5% and 29.7%, respectively. Patients who underwent surgery had better 3-year and 5-year OS rates than those treated without surgery (40.7% and 34.1% vs 21.4% and 14.3%, respectively), and the same was true for patients treated with and without biotherapy (58.2% and 50.9% vs 30.0% and 23.4%, respectively). Distant metastasis at presentation was associated with a worse prognosis. Those patients managed with multimodality treatment had better OS rates., Conclusion: The prognosis in SMM is poor, particularly for those with distant metastasis or without surgery. Multimodality treatment may improve survival., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: Hypoparathyroidism is one of the most serious complications of thyroidectomy. It is important to identify the parathyroid glands during thyroidectomy. In order to find an economic, simple and less traumatic way to identify the parathyroid glands and testify its feasibility, fine-needle aspiration of suspected parathyroid tissue was used to measure the parathyroid hormone (PTH) levels during the surgical procedure., Methods: From Nov. 2011 to Apr. 2012, 50 patients were recruited for thyroid surgery in the Sun Yat-sen University Cancer Centre. During surgery, fine-needle aspiration of suspected tissues, including parathyroid gland, thyroid gland, muscle, fat tissue, and lymph node, was performed, the PTH levels were measured. In addition, the tissues above-mentioned were taken to pathological examination. Statistical processing was adopted to determine the sensitivity and specificity of intraoperative fine-needle aspiration with measurement of PTH level in finding the pathology of the parathyroid gland., Results: There were 237 tissues from 50 patients in total, and 45 of them were certified as the parathyroid glands by pathology. Intra-operative PTH (ioPTH) of the tissues in forty-four cases were higher than 600 ng/L, ioPTH of the tissues in one case was lower than 600 ng/L, and it was 160 ng/L. The highest ioPTH in other cases was 537.7 ng/L. The sensitivity was 97.8%. The specificity was 100%. The difference between the sensitivity and the specificity of two groups was not statistically significant, and P > 0.05. The level of PTH of parathyroid gland were much higher than other tissues, and P < 0.001., Conclusions: The level of ioPTH of parathyroid gland were far higher than thyroid, muscle, fat, lymph node. It is an economic, fast and less traumatic way to identify the parathyroid gland by using the fine-needle aspiration of the parathyroid tissue with measurement of PTH levels. The sensitivity and the specificity are high. It can be used in the thyroidectomy to identify the parathyroid glands.

In this paper, we present a lab-in-a-droplet bioassay strategy for a centrifugal microfluidics or lab-on-a-disc (LOAD) platform with three important advancements including density difference pumping, power to disc and bidirectional flow control. First, with the water based bioassay droplets trapped in a micro-channel filled with mineral oil, centrifugal force due to the density difference between the water and oil phases actuates droplet movement while the oil based medium remains stationary. Second, electricity is coupled to the rotating disc through a split-core transformer, thus enabling on-chip real-time heating in selected areas as desired and wireless programmable functionality. Third, an inertial mechanical structure is proposed to achieve bidirectional flow control within the spinning disc. The droplets can move back and forth between two heaters upon changing the rotational speed. Our platform is an essential and versatile solution for bioassays such as those involving DNA amplification, where localized temperature cycling is required. Finally, without the loss of generality, we demonstrate the functionality of our platform by performing real-time polymerase chain reaction (RT-PCR) in a linear microchannel made with PTFE (Teflon) micro-tubing.

This report describes a novel diagnostic assay for rapid detection of the Panton-Valentine Leukocidin (PVL) toxin of methicillin-resistant Staphylococcus aureus (MRSA) utilizing resistive pulse sensing (RPS), loop-mediated isothermal DNA amplification (LAMP) in combination with gold nanoparticles (AuNPs). The PVL DNA from MRSA was specifically amplified by LAMP using four primers at one temperature (65 °C). The DNA products with biotin were then conjugated to a first AuNP1 (55±2 nm) through biotin-avidin binding. A second AuNP2 (30±1.5 nm) coated with a specific DNA probe hybridized with the LAMP DNA products at the loop region to enhance assay sensitivity and specificity, to generate supra-AuNP1-DNA-AuNP2 assemblies. Scanning electron microscopy confirmed the presence of these supra-assemblies. Using RPS, detection and quantitation of the agglomerated AuNPs were performed by a tunable fluidic nanopore sensor. The results demonstrate that the LAMP-based RPS sensor is sensitive and rapid for detecting the PVL DNA. This technique could achieve a limit of detection (LOD) up to about 500 copies of genomic DNA from the bacteria MRSA MW2 and the detection can be completed within two hours with a straightforward signal-to-readout setup. It is anticipated that this LAMP-based AuNP RPS may become an effective tool for MRSA detection and a potential platform in clinical laboratory to report the presence or absence of other types of infectious agents., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to describe a new technique of combined hyoid bone and thyrohyoid membrane flap in laryngeal reconstruction after tumor resection, and to evaluate outcome., Methods: Six patients requiring an frontal partial laryngectomy for cancer were enrolled between September 2008 and August 2012., Results: Nasogastric feeding was initiated within 24 hours. The mean times to swallow batter, ability to drink water and removal of the nasogastric tube were 2.6, 5.5 and 6.3 days. All patients had good respiratory function. There were no deaths, and no reports of postoperative dyspnea or dysphagia. The vocal quality was satisfactory, slightly deeper and raspy, and the volume was weak when calling. The final follow-up assessment was in August 2012, and the overall mean follow-up period was 29.5months, range 14 to 47 months. Case two subsequently underwent total laryngectomy for recurrence in the paraglottic space, but there was no evidence of further tumor recurrence at the final assessment., Conclusions: The combined muscle-pedicle hyoid bone and thyrohyoid membrane flap is a reliable graft for one-stage repair of laryngotracheal defects, providing effective repair of the mucosa and cartilage support. Vocal quality, swallowing function and ventilation after the procedure were favorable.

Patients undergoing extensive partial laryngectomy require laryngeal reconstruction to restore function. Several techniques have been described, but they are associated with complications such as laryngeal stenosis. The aim of this study was to describe a new technique of combined hyoid bone and thyrohyoid membrane flap in laryngeal reconstruction after tumor resection, and to evaluate outcome. Eight patients requiring an extensive vertical or frontal partial laryngectomy for cancer were enrolled. Following radical tumor resection, laryngeal reconstruction was performed using the hyoid bone with a thyrohyoid membrane flap. Postoperative recovery time, complications, vocal quality, and cancer outcome were evaluated. The procedure was successful in all patients. There were no deaths, and no reports of postoperative dyspnea or dysphagia. Decannulation was performed in all patients after a median duration of 3 days (range 2-5 days). Swallowing and respiratory function were satisfactory and laryngeal stenosis did not occur during the mean follow-up period of 30.5 months. One patient had a local recurrence and required a salvage operation. A combined hyoid bone and thyrohyoid membrane flap is a reliable and relatively safe procedure that can be successfully performed for laryngeal reconstruction after extensive vertical or frontal partial laryngectomy.

In order to provide a basis for clinical treatment decisions, we explored whether there was a correlation between the expression of COX-2 and P300 and clinical factors in a group of patients with laryngeal squamous cell carcinoma (LSCC). A retrospective analysis of clinicopathological data was conducted in 80 patients with LSCC who presented between January 1997 and December 1998. An immunohistochemistry tissue microarray was conducted of 80 surgically resected LSCC and 20 adjacent normal tissue specimens. Survival analysis and Kaplan-Meier curves were used to compare the effects of clinicopathological factors on survival. The Cox model was applied for multivariate analysis. The expression level of COX-2/P300 in LSCC tissues and adjacent normal tissues were 47.5/50.0 versus 0.0/15.0 %. The expression of COX-2 and P300 was correlated with higher T category, N category, clinical staging, histological grade and recurrence (P < 0.05). P300 expression was correlated with COX-2 expression (P < 0.05). Univariate survival analysis showed that P300, COX-2, N category, clinical staging and recurrence factors were closely correlated with unfavorable survival (P < 0.05). Multivariate analysis showed that COX-2 expression, histological grade and recurrence were independent prognostic factors for LSCC. High expression levels of COX-2 and P300 indicated poor survival outcomes for patients with LSCC.

Skin paddle necrosis and neck function damage, particularly rotation, are two problems associated with the infrahyoid myocutaneous flap clinical application. The aim of this study was to investigate vessel supply and drainage of the skin paddle and to report our modified flap incision technique. In this work, we conducted a cadaveric study and reviewed our experience with the modified incision and describe the surgical procedure. We confirmed the platysma muscle branch feeds the skin paddle overlying the infrahyoid myocutaneous flap. The length between the platysma muscle branch entry point and its originating point measured 3.38 (min 2.51, max 4.52) cm. The flap has two drainage systems. The skin paddle of the flap was drained by the anterior jugular vein and external jugular vein, respectively, or both. The infrahyoid muscles were drained by the superior thyroid vein. In the early four cases, where the platysma muscle branch was not protected, skin paddle necrosis appeared in two cases. In the later seven cases, which involved preservation of the platysma muscle branch, all flaps successfully survived. Patients in whom a modified incision was used all achieved both satisfactory rehabilitation of neck function and an adequate esthetic result. We conclude that the necrosis rate of the skin paddle of the flap can be reduced by carefully protecting its supply and drainage vessels. The modified incision can improve neck function postoperatively.