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ARGO-YBJ is a full coverage layer of Resistive Plate Counters (RPCs) covering an area of about 5.800 m 2 to be installed at the YangBaJing Laboratory (Tibet, China) at 4.300 m a.s.l . The DAQ system is based on a Central Station which receives the detector information from distributed readout electronics. Data from each RPC are acquired from a Receiver Card which reads out and digitizes the space and time information from 10 pick-up pads and gives out the pad multiplicity for trigger purposes. The Receiver Cards are hosted in Local Stations which Group 12 RPCs. On trigger occurrence, each Local Station sends the collected data to the Central Station. Both the detector and the electronics allow 1 ns accuracy in time measurements. In this work a detailed description of the Local Station and the Trigger System are presented.

Ultra-precision raster milling induces external stress to cause phase changes of Zn–Al alloy at a thin surface layer, which further degrade surface integrity of high-precision components. This study focuses on discussing phase changes at the surfaces of the alloy after ultra-precision raster milling under the high cutting speeds of 680 m/min, 1120 m/min, and 1360 m/min. Along with the penetration depth at the machined surfaces, phase changes and surface hardening rapidly declined to vanish with crystal orientation shift back to its standard Bragg angle. As the cutting speeds increased, phase changes, crystal orientation shift, and surface hardening obviously decreased with phase change thicknesses from 323 nm, 241 nm to 87 nm. It is worth noticing that at a high cutting speed phase changes at the machined surface can be greatly reduced to a significant degree.

Xin Huang,1,2,* Fu-Qing Zhou,3,* Yu-Xiang Hu,1 Xiao-Xuan Xu,1 Xiong Zhou,4 Yu-Lin Zhong,1 Jun Wang,4 Xiao-Rong Wu1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, 2Department of Ophthalmology, The First People’s Hospital of Jiujiang City, Jiujiang, 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Medical Imaging Research Institute, 4Second Department of Respiratory Disease, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Objective: Many previous reports have demonstrated significant neural anatomy changes in the brain of high myopic (HM) patients, whereas the spontaneous brain activity changes in the HM patients at rest are not well studied. Our objective was to use amplitude of low-frequency fluctuation (ALFF) method to investigate the changes in spontaneous brain activity in HM patients and their relationships with clinical features. Methods: A total of 38 patients with HM (17 males and 21 females) and 38 healthy controls (HCs) (17 males and 21 females) closely matched in age, sex, and education underwent resting-state functional magnetic resonance imaging scans. The ALFF method was used to assess local features of spontaneous brain activity. The relationship between the mean ALFF signal values in many brain regions and the clinical features in HM patients was calculated by correlation analysis. Results: Compared with HCs, the HM patients had significantly lower ALFF in the right inferior and middle temporal gyrus, left middle temporal gyrus, left inferior frontal gyrus/putamen, right inferior frontal gyrus/putamen/insula, right middle frontal gyrus, and right inferior parietal lobule and higher ALFF values in the bilateral midcingulate cortex, left postcentral gyrus, and left precuneus/inferior parietal lobule. However, no relationship was found between the mean ALFF signal values of the different areas and the clinical manifestations in HM. Conclusion: The HM patients were affected with brain dysfunction in many regions, which may indicate the presence of neurobiological changes involving deficits in language understanding and attentional control in HM patients. Keywords: ALFF, high myopic, resting state, functional magnetic resonance imaging

Meng-Zhu Yao,1 Ming-Yi Huang-Fu,1 Hui-Na Liu,1 Xia-Rong Wang,1 Xiaoxia Sheng,2 Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 2Hangzhou SoliPharma Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China Abstract: Nano-hydroxyapatite/polyamide 66 (nHA/PA66) porous scaffolds were fabricated by a phase inversion method. Carbon nanotubes (CNTs) and silk fibroin (SF) were used to modify the surface of the nHA/PA66 scaffolds by freeze-drying and cross-linking. Dexamethasone was absorbed to the CNTs to promote the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). The cell viability of BMSCs was investigated by changing the concentration of the CNT dispersion, and the most biocompatible scaffold was selected. In addition, the morphology and mechanical property of the scaffolds were investigated. The results showed that the nHA/PA66 scaffolds modified with CNTs and SF met the requirements of bone tissue engineering scaffolds. The dexamethasone-loaded CNT/SF-nHA/PA66 composite scaffold promoted the osteogenic differentiation of BMSCs, and the drug-loaded scaffolds are expected to function as effective bone tissue engineering scaffolds. Keywords: BMSCs, tissue engineering, porous scaffold, carbon nanotubes, silk fibroin, surface modification, dexamethasone

Xinxin Yan,1,2 Wen Yang,3 Zengwu Shao,1 Shuhua Yang,1 Xianzhe Liu1 1Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Orthopaedic Surgery, Wuhan Third Hospital, 3Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Abstract: Carbon nanomaterials are becoming increasingly significant in biomedical fields since they exhibit exceptional physicochemical and biocompatible properties. Today, the stem cells offer potentially new therapeutic approaches in tissue engineering and regenerative medicine. However, the induction of differentiation into specific lineages remains challenging, which provoked us to explore the biomedical applications of carbon nanomaterials in stem cells. In this study, we investigated the interactions between graphene/single-walled carbon nanotube (G/SWCNT) hybrids and rat mesenchymal stem cells (rMSCs) and focused on the proliferation and differentiation of rMSCs treated with G/SWCNT hybrids. Cell viability and morphology were evaluated using cell counting kit-8 assay and immunofluorescence staining, respectively. Osteogenic differentiation evaluated by alkaline phosphatase activity of MSCs proved to be higher after treatment with G/SWCNT hybrids, and the mineralized matrix nodule formation was also enhanced. In addition, the expression levels of osteogenic-associated genes were upregulated, while the adipocyte-specific markers were downregulated. Consistent with these results, we illustrated that the effect of G/SWCNT hybrids on the process of osteogenic differentiation of rMSCs can be modulated by activating the p38 signaling pathway and inhibiting the extracellular signal-regulated kinase 1/2 pathway. Nevertheless, our study suggests that carbon nanomaterials offer a promising platform for regenerative medicine in the near future. Keywords: carbon-based nanomaterials, 3D nanostructure, stem cell therapy, bone formation

Lu Lv, Weidong Hu, Yanchen Ren, Xiaoxuan Wei Hubei Key Laboratory of Tumor Biological Behaviors, Department of Thoracic Oncology, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China Background and objectives: The safety and effectiveness of minimally invasive esophagectomy (MIE) in comparison with the open esophagectomy (OE) remain uncertain in esophageal cancer treatment. The purpose of this meta-analysis is to compare the outcomes of the two surgical modalities. Methods: Searches were conducted in MEDLINE, EMBASE, andClinicalTrials.govwith the following index words: “esophageal cancer”, “VATS”, “MIE”, “thoracoscopic esophagectomy”, and “open esophagectomy” for relative studies that compared the effects between MIE and OE. Random-effect models were used, and heterogeneity was assessed. Results: A total of 20 studies were included in the analysis, consisting of four randomized controlled trials and 16 prospective studies. MIE has reduced operative blood loss (P=0.0009) but increased operation time (P=0.009) in comparison with OE. Patients get less respiratory complications (risk ratio =0.74, 95% CI =0.58–0.94, P=0.01) and better overall survival (hazard ratio =0.54, 95% CI =0.42–0.70, P

Xin-Xing Wang,1,2,* Ying-Ying Zha,3,* Bo Yang,1 Lin Chen,1,2 Ming Wang1,2 1CAS Key Laboratory of Brain Function and Diseases, 2Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 µM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO) synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. Keywords: fullerenol, hippocampal slice, nitric oxide synthase, synaptic plasticity, oxidative stress

Kang Lin,1,* Tao Xu,1,* Bang-Shun He,1 Yu-Qin Pan,1 Hui-Ling Sun,1 Hong-Xin Peng,2 Xiu-Xiu Hu,2 Shu-Kui Wang1 1Central Laboratory, Nanjing First Hospital, Nanjing Medical University, 2Medical School, Southeast University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Lung cancer is one of the leading causes of cancer death worldwide. Accumulating evidence has indicated that microRNAs (miRNAs) can be proposed as promising diagnostic and prognostic markers for various cancers. The current study analyzed the miRNA expression profiles of 418 lung adenocarcinoma (LUAD) cases obtained from The Cancer Genome Atlas dataset, with the aim to investigate the relationship of miRNAs with progression and prognosis of LUAD. A total of 185 miRNAs were found to be differentially expressed between LUAD tumor tissues and adjacent normal tissues. Among them, 13, 10, 0, and 10 miRNAs were discovered to be associated with pathologic T, N, M, and Stage, respectively. Interestingly, mir-200 family (mir-200a, mir-200b, and mir-429) was shown to play a critical role in the progression of LUAD. In the multivariate Cox regression analysis, mir-1468 (P=0.009), mir-212 (P=0.026), mir-3653 (P=0.012), and mir-31 (P=0.002) were significantly correlated with recurrence-free survival. With regard to overall survival, mir-551b (P=0.011), mir-3653 (P=0.016), and mir-31 (P=0.001) were proven as independent prognostic markers. In summary, this study identified the cancer-specific miRNAs that may predict the progression and prognosis of LUAD. Keywords: microRNA, progression, prognosis, lung adenocarcinoma

Haiying Li,1 Tingting Pan,1 Ying Cui,1 Xiaxia Li,1 Jiefang Gao,1 Wenzhi Yang,1 Shigang Shen2 1Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmacy, 2Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, People’s Republic of China Abstract: The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), ­Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM. Keywords: glimepiride, microemulsion, solubility, pharmacodynamics, pharmacokinetics

Jiong Chen,1,2,* Xing-Xing Zhu,1,2,* Hong Xu,1,2 Heng-Zhong Fang,1,2 Jin-Qian Zhao1,21Department of General Surgery, Anhui Provincial Hospital, Anhui Medical University, 2Anhui Provincial Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, People’s Republic of China *These authors contributed equally to this work Background: Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers.Materials and methods: Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs.Results: Statistics showed that high expression of membrane ULBP1 was a good biomarker of overall survival (18 months vs 13 months), and a high level of soluble ULBP2 was deemed an independent poor indicator for both overall survival (P

Fu-Yan Lv,1,* Rui-Hua Dong,1,* Zhao-Jian Li,2,* Chong-Chong Qin,1 Xu Yan,1,3 Xiao-Xiao He,1 Yu Zhou,4 Shi-Ying Yan,1 Yun-Ze Long1,3 1Collaborative Innovation Center for Nanomaterials & Optoelectronic Devices, College of Physics, Qingdao University, 2Department of Neurosurgery, Affiliated Hospital of Qingdao University, 3Industrial Research Institute of Nonwovens & Technical Textiles, College of Textiles & Clothing, 4Medical College, Qingdao University, Qingdao, People’s Republic of China *These authors contributed equally tothis work Purpose: In this work, we propose an in situ precise electrospinning of medical glue fibers onto dural wound for improving sealing capability, avoiding tissue adhesion, and saving time in dural repair.Methods: N-octyl-2-cyanoacrylate, a commercial tissue adhesive (medical glue), can be electrospun into ultrathin fibrous film with precise and homogeneous deposition by a gas-assisted electrospinning device.Results: The self-assembled N-octyl-2-cyanoacrylate film shows high compactness and flexibility owing to its fibrous structure. Simulation experiments on egg membranes and goat meninges demonstrated that this technology can repair small membrane defects quickly and efficiently.Conclusion: This method may have potential application in dural repair, for example, working as an effective supplementary technique for conventional dura suture. Keywords: cyanoacrylates, electrospun fibers, in situ repair dural, gas-assisted electrospinning apparatus

Weisun Huang,1 Weiwei Nie,1 Wenwen Zhang,2 Yanru Wang,1 Aiyu Zhu,1 Xiaoxiang Guan1,2 1Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China Background: The ER signaling pathway plays a critical role in breast cancer. ER signaling pathway-related proteins, such as TRX, AR, and cyclin D1, may have an important function in breast cancer. However, the ways that they influence breast cancer development and progression are still unclear.Patients and methods: A total of 101 Chinese female patients diagnosed with invasive ductal breast adenocarcinoma were retrospectively enrolled in the study. The expression levels of TRX, AR, and cyclin D1 were detected by immunohistochemistry and analyzed via correlation with clinicopathological characteristics and the expression status of ER, PR, and HER2.Results: The expression status of TRX, AR, and cyclin D1 was not associated with the patient’s age, menopausal status, tumor size, or histological differentiation (P>0.05), but was positively correlated with ER and PR (P

Long Chen,1,2,* Huixin Yang,1,* Yanbin Xiao,3,* Xiaoxia Tang,4 Yuqian Li,1 Qiaoqiao Han,1 Junping Fu,3 Yuye Yang,1 Yuechun Zhu1 1Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2PET/CT Center, Yunan Tumor Hospital, the Third Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Department of Orthopaedics, Yunan Tumor Hospital, the Third Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 4Department of Pharmacy, the Second Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, Yunnan, People’s Republic of China *These authors contributed equally to this work Abstract: The present study intended to demonstrate the effects of long noncoding RNA growth arrest-specific transcript 5 (GAS5) on the migration and invasion of melanoma cells. We first detected the expression of GAS5 among four kinds of melanoma cell lines, followed by constructing GAS5-knocked down and overexpressed stable cells. Next, we evaluated the effects of GAS5 on cell migration and invasion using wound healing and gelatin zymography assays. Finally, melanoma cells with different GAS5 expression were injected into nude mice, and the tumor volumes were recorded and tumor tissues were analyzed after sacrificing the mice. This study systematically examined the function of GAS5 in mediating melanoma metastasis and revealed that GAS5 plays an anticancer role in melanoma via regulating gelatinase A and B, both in vitro and in vivo. Keywords: lncRNA, GAS5, melanoma, metastasis, gelatinase

Hong-xing Li,1,* Xiao-xiao Peng,1,2,* Qiang Zong,1 Kai Zhang,1 Ming-xin Wang,1 Yi-zhe Liu,1 Guang-liang Han1 1Department of Neurosurgery, Shengli Oilfield Central Hospital, 2Department of Intensive Care Unit, Dongying, Shandong, People’s Republic of China *These authors contributed equally to this work Background: Cigarette smoking has been shown to be a risk factor for adult glioma by some but not all studies. We conducted a meta-analysis to systematically assess the potential association. Methods: PubMed and EMBASE were searched from the date of their inception to October1, 2015, to identify relevant articles. Reference lists from these articles were reviewed to identify additional studies. Both cohort and case–control studies were included. Fixed-effects models were used to calculate the overall relative risk (RR) with corresponding 95% confidence intervals (CIs). Results: The final analysis included 24 studies (seven cohort and 17 case–control studies), involving more than 2.3 million individuals. The combined RR was 1.04 (95% CI: 1.00, 1.09; P=0.073) for ever-smokers, 0.97 (95% CI: 0.88, 1.07; P=0.574) for current-smokers, and 1.07 (95% CI: 0.98, 1.16; P=0.130) for past smokers, with little evidence of heterogeneity. Omission of any single study from the analysis had little effect on the result. No evidence of publication bias was found. A small but statistically significant increase was found in past smokers in females (RR: 1.13, 95% CI: 1.00, 1.28; P=0.046) but not in males. Conclusion: In general, there was no association between cigarette smoking and adult glioma. The small but statistically significant association in females requires further investigation. Keywords: cigarette smoking, glioma, meta-analysis, risk

Xi-Xi Lai, Ren-Ai Xu, Yu-Ping Li, Han Yang Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC.Methods: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR) and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials.Results: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55), hypertension (RR =5.34), and hemorrhagic events (RR =2.61). No statistically significant differences were found for gastrointestinal perforation (P=0.60), arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively), or fatal events (P=0.29).Conclusion: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. Keywords: toxicities, angiogenesis inhibitors, non-small-cell lung carcinoma, meta-analysis, safety

This work presents an experimental study on the dispersal characteristics of a liquid jet ejecting into vacuum. The liquid breaking experiments of several kinds of liquid under different pressure and temperature conditions are carried out in a flash chamber. The stability of the jet and the sizes of the droplets or the icing particles formed during liquid flashing dispersing are analyzed. The influences of the superheat degree, spray velocity, and the mass of the volatile liquid mixing in the nonvolatile liquid on these characteristics are discussed. Moreover, the applicability of the two definitions of superheat degree is discussed. The results show that the superheat degree is an important parameter influencing the pattern of the breaking liquid, and the jet velocity has a large influence on the distribution of particle sizes. In addition, mixing some volatile liquid with nonvolatile liquid can enhance the dispersion of the latter.

Aihong Meng,1 Xiaopeng Zhang,2 Siyu Wu,1 Mingxia Wu,1 Jing Li,1 Xixin Yan,1 Kamilla Kopec-Harding,3 Jiakai Wu41Respiratory Division, The Second Hospital of Hebei Medical University, 2Department of Thoracic Surgery, Hebei Province General Hospital, Shijiazhuang, Hebei, Peoples’ Republic of China; 3Centre for Musculoskeletal Research, 4Centre for Respiratory and Allergy, Institute of Inflammation and Repair, University of Manchester, Manchester, UKBackground: Systemic inflammation and steroid resistance are the hallmarks of COPD. We examined the impact of p38 inhibitor (SB203580) in in vitro assays of systemic inflammation using pulmonary cells and patients’ sera.Objective and methods: Data from 66 COPD patients and 15 age-/sex-matched healthy controls were compared. Interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and CCL5 were measured in serum samples and culture media from peripheral blood mononuclear cells. The impact of sera on IL-10 and CCL5 expression in alveolar macrophage cell line (MH-S) was examined. The in vitro effects of SB203580 on lipopolysaccharide-induced inflammation were investigated.Results: Peripheral blood mononuclear cells from Global Initiative for Chronic Obstructive Lung Disease (GOLD) D patients produced more CCL5 and TNF-α, and less IL-10 compared to GOLD A–C patients. SB203580 treatment suppressed CCL5 and TNF-α and stimulated IL-10 production; however, the effect of SB203580 on IL-10 was lower in the COPD group. Culture of MH-S cells with COPD serum showed a significant increase in CCL5 and a significant decrease in IL-10 compared to healthy serum. This effect was not suppressed with SB203580 treatment.Conclusion: COPD serum has a potent proinflammatory effect on pulmonary cells. Inhibition of p38 phoshorylation had a limited effect in restoring impaired lymphocyte function and suppressing inflammation induced by COPD serum, implying important p38-independent inflammatory mechanisms in COPD. Keywords: COPD, p38MAPK inhibitor, macrophage, CCL5, TNF-α, IL-10

Tao Qin,1,* Ningning Zhou,1,* Yin-duo Zeng,2 Xiaoxiao Dinglin,2 Yuanyuan Zhao,1 Huai Liu,3,4 Likun Chen1 1Department of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Breast Tumor Center, Sun Yat-sen University Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, 3Department of Radiotherapy, Hunan Cancer Hospital, 4Department of Radiotherapy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Key Laboratory of Translational Radiation Oncology, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Background: High lactate dehydrogenase (LDH) is associated with a large tumor burden in extensive-disease small-cell lung cancer (ED-SCLC). This study evaluated the benefit of additional thoracic radiotherapy (TRT) in patients with ED-SCLC with elevated LDH.Methods: We analyzed 94 patients with ED-SCLC and evaluated LDH at Sun Yat-sen University Cancer Center during the period between January 2000 and March 2010. Patients were divided into two groups according to whether TRT was received. Survival was evaluated by the Kaplan–Meier method and Cox’s regression analysis.Results: The median age of the 94 patients with ED-SCLC was 58.5years. The main metastatic sites included the liver, bone, brain, and adrenal glands. The response rate in the TRT group was 46.9%. There were 32 patients (34.04%) receiving TRT and 5.3% receiving prophylactic cranial irradiation. The median survival time reached 10months (95% confidence interval: 8.22, 11.78months), and the 1-, 2-, and 5-year survival rates were 43.6%, 11.7%, and 2.1%, respectively. There was a significant difference in the median progression-free survival (PFS) and overall survival (OS) between the TRT group and the no TRT group (PFS: 9.0months vs 6.0months, P=0.018; OS: 13.0months vs 9.0months, P=0.006).Conclusion: The use of TRT improves the survival of patients with ED-SCLC. Future studies should use the LDH level for categorizing patients for treatment. Keywords: small-cell lung cancer, extensive stage, thoracic radiotherapy, LDH

Minhua Wu,1,2,* Xiaoxia Ye,2,* Xubin Deng,3,* Yanxia Wu,4 Xiaofang Li,4 Lin Zhang11Department of Histology and Embryology, Southern Medical University, Guangzhou, 2Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, 3Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University, Guangzhou, 4Pathological Diagnosis and Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’sRepublic of China*These authors contributed equally tothis workAims: Metastasis-associated gene 2 (MTA2) is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC). The aim of the study was to explore the expression and function of MTA2 in NPC.Methods: Expression of MTA2 in NPC tissues and cell lines was detected by immunohistochemistry and Western blotting. Relationship between MTA2 expression and clinicopathological features was analyzed. Stable MTA2-overexpressing and MTA2-siliencing NPC cells were established by transfection with plasmids encoding MTA2 cDNA and lentivirus-mediated short hairpin RNA, respectively. Cell viability was determined by Cell Counting Kit-8 and colony formation assay. Cell migration ability was evaluated by wound healing and transwell invasion assay. The impact of MTA2 knockdown on growth and metastasis of CNE2 cells in vivo was determined by nude mouse xenograft models. Expression of several Akt pathway proteins was detected by Western blotting.Results: MTA2 was upregulated in NPC tissues and three NPC cell lines detected (CNE1, CNE2, and HNE1). MTA2 expression was related to clinical stage and lymph node metastasis of patients with NPC. MTA2 upregulation promoted proliferation and invasion of CNE1 cells, while MTA2 depletion had opposite effects on CNE2 cells. Moreover, MTA2 depletion suppressed growth and metastasis of CNE2 cells in vivo. MTA2 overexpression activated Akt and upregulated the expression of matrix metalloproteinase 7 and cyclin D1.Conclusion: We conclude that MTA2 acts as an oncogene in tumorigenesis of NPC. MTA2 may be a potential target for gene therapy in NPC.Keywords: MTA2, nasopharyngeal carcinoma, proliferation, invasion, Akt pathway

Hao Zhang,1 Chen Liang,2 Xinxin Hou,3 Ling Wang,1 Dongsheng Zhang41Department of Imaging and Nuclear Medicine, Medical School of Southeast University, Nanjing, Jiangsu, 2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 3Department of Pathology, Medical School of Henan Polytechnic University, Jiaozuo, Henan, 4Jiangsu Key Laboratory for Biomaterials andDevices, Medical School, Southeast University, Nanjing, People’sRepublicof ChinaAbstract: Combination therapy for lung cancer has garnered widespread attention. Radiation therapy, gene therapy, and molecular targeted therapy for lung cancer have certain effects, but the disadvantages of these treatment methods are evident. Combining these methods can decrease their side effects and increase their curative effects. In this study, we constructed a pYr-ads-8-5HRE-cfosp-iNOS-IFNG plasmid (a gene circuit that can express IFNγ), which is a gene circuit, and used that plasmid together with C225 (cetuximab) to prepare gene-loaded immunomagnetic albumin nanospheres (IMANS). Moreover, we investigated the therapeutic effects of gene-loaded IMANS in combination with radiation therapy on human lung cancer in vitro and in vivo. The results showed that this gene circuit was successively constructed and confirmed that the expression of INFγ was increased due to the gene circuit. Gene-loaded IMANS combined with radiation therapy demonstrated improved results in vitro and in vivo. In conclusion, gene-loaded IMANS enhanced the efficacy of combination therapy, solved problems related to gene transfer, and specifically targeted lung cancer cells.Keywords: gene circuit, combination therapy, magnetic albumin nanospheres

Da-Fu Zhang,* Zhen-Hui Li,* De-Pei Gao, Guang-Jun Yang, Ying-Ying Ding, Guan-Shun Wang, Xing-Xiang Dong Department of Radiology, The Third Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, People’s Republic of China *These authors contributed equally tothis work Abstract: Ewing’s sarcoma/primary neuroectodermal tumor (EWS/PNET) is an extraordinarily rare primary tumor of the kidney with characteristic histology. To date, the imaging features of EWS/PNET have not been clearly described. Here, we report two cases of EWS/PNET confirmed by fine-needle aspiration biopsy and analyze the findings of computed tomography and ultrasound. The radiological features of EWS/PNET are presented along with a brief review of the pertinent literature to have a further understanding of EWS/PNET’s imaging features. Keywords: Ewing’s sarcoma, neuroectodermal tumor, X-ray computed tomography, histology, ultrasound

Ren-ai Xu,1,* Er-min Gu,2,* Quan Zhou,2 Lingjing Yuan,2 Xiaoxia Hu,2 Jianping Cai,3 Guoxin Hu1,2 1Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, 2Department of Pharmacology, School of Pharmacy, Wenzhou Medical University, Wenzhou, 3The Key Laboratory of Geriatrics, Beijing Hospital & BeijingInstitute of Geriatrics, Ministryof Health, Beijing, People’s Republic of China *These authors contributed equally tothis work Background: CYP2D6 is one of the most important members of the cytochrome P450 superfamily. Its genetic polymorphism significantly influences the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. Methods and results: The aim of this research was mainly to explore the catalytic activities of 22 newly reported CYP2D6 isoforms (2D6*87, *88, *89, *90, *91, *92, *93, *94, *95, *96,*97, *98, *R25Q, F164L, E215K, F219S, V327M, D336N, V342M, R344Q, R440C, R497C) on dapoxetine in vitro. The research was designed with an appropriate incubation system in test tubes and carried out in the constant temperature water. Through detecting its two metabolites desmethyldapoxetine and dapoxetine-N-oxide, the available data were obtained to explain the influence of CYP2D6 polymorphism on the substrate drug dapoxetine. As a result, the intrinsic clearance (Vmax/Km) values of most variants were significantly altered when compared with the counterpart of CYP2D6*1, with most of these variants exhibiting either reduced Vmax and/or increased Km values. For dapoxetine demethylation pathway (which produces desmethyldapoxetine), 2D6*89 and E215K exhibited no markedly decreased relative clearance of 92.81% and 97.70%, respectively. The relative clearance of rest 20 variants exhibited decrease in different levels, ranging from 20.44% to 90.90%. For the dapoxetine oxidation pathway (which produces dapoxetine-N-oxide), the relative clearance values of three variants, 2D6*90, *94, and V342M, exhibited no markedly increased relative clearance of 106.17%, 107.78%, and 109.98%, respectively; the rest 19 variants exhibited significantly decreased levels ranging from 27.56% to 84.64%. In addition, the kinetic parameters of two CYP2D6 variants (2D6*92 and 2D6*96) could not be detected, due to the defect of the CYP2D6 gene. Conclusion: As the first report of all aforementioned alleles for dapoxetine metabolism, these data may help in the clinical assessment of the metabolic elimination of dapoxetine and may provide fundamental information for further clinical studies. Keywords: genetic polymorphism, CYP2D6 variants, drug metabolism, dapoxetine, personalized treatment

Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally tothis workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368) of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of lung adenocarcinoma with unique clinicopathological features.Keywords: KRAS, NSCLC, surgery, prognosis

Ming Yan,1,* Yun Zhang,2,* Haiyan Qin,3 Kezhou Liu,1 Miao Guo,1 Yakun Ge,1 Mingen Xu,1 Yonghong Sun,4 Xiaoxiang Zheng4 1Department of Biomedical Engineering, College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou, 2Basic Medical Sciences, College of Medicine, Shaoxing University, Shaoxing, 3Department of Chemistry, Zhejiang University, 4Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Department of Biomedical Engineering, Zhejiang University, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Cadmium telluride quantum dots (CdTe QDs) have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs). However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER) in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (–21.63±0.91mV), with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95.52% by energy depletion (NaN3/deoxyglucose or low temperature). The endocytosis inhibitors (methyl-β-cyclodextrin, genistein, sucrose, chlorpromazine, and colchicine) dramatically decreased the uptake of CdTe QDs by HUVECs, suggesting that both caveolae/raft- and clathrin-mediated endocytosis were involved in the endothelial uptake of CdTe QDs. Using immunocytochemistry, a striking overlap of the internalized CdTe QDs and ER marker was observed, which indicates that QDs may be transported to ER. The CdTe QDs also caused remarkable ER stress responses in HUVECs, confirmed by significant dilatation of ER cisternae, upregulation of ER stress markers GRP78/GRP94, and activation of protein kinase RNA-like ER kinase-eIF2α-activating transcription factor 4 pathway (including phosphorylation of both protein kinase RNA-like ER kinase and eIF2α and elevated level of activating transcription factor 4). CdTe QDs further promoted an increased C/EBP homologous protein expression, phosphorylation of c-JUN NH2-terminal kinase, and cleavage of ER-resident caspase-4, while the specific inhibitor (SP600125, Z-LEVD-fmk, or salubrinal) significantly attenuated QDs-triggered apoptosis, indicating that all three ER stress-mediated apoptosis pathways were activated and the direct participation of ER in the CdTe QDs-caused apoptotic cell death in HUVECs. Our findings provide important new insights into QDs toxicity and reveal potential cardiovascular risks for the future applications of QDs. Keywords: quantum dots, human umbilical vein endothelial cells, endocytosis, ER stress, apoptosis

Tong Hao,1,2,* Jin Zhou,2,* Shuanghong Lü,3,* Boguang Yang,2,4 Yan Wang,2 Wancai Fang,2,4 Xiaoxia Jiang,2 Qiuxia Lin,2 Junjie Li,2 Changyong Wang1,21School of Life Science and Technology, Harbin Institute of Technology, Harbin, 2Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 3Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, 4Department of Polymer Science, Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People’s Republic of China*These authors contributed equally tothis workAbstract: Zero-dimensional fullerenes can modulate the biological behavior of a variety of cell lines. However, the effects and molecular mechanisms of proliferation and cardiomyogenic differentiation in brown adipose-derived stem cells (BADSCs) are still unclear. In this study, we report the initial biological effects of fullerene-C60 on BADSCs at different concentrations. Results suggest that fullerene-C60 has no cytotoxic effects on BADSCs even at a concentration of 100µg/mL. Fullerene-C60 improves the MAPK expression level and stem cell survival, proliferation, and cardiomyogenesis. Further, we found that the fullerene-C60 modulates cardiomyogenic differentiation. Fullerene-C60 improves the expression of cardiomyocyte-specific proteins (cTnT and α-sarcomeric actinin). At elevated concentration, fullerene-C60 reduces the incidence of diminished spontaneous cardiac differentiation of BADSCs with time. At the genetic level, fullerene-C60 (5µg/mL) also improves the expression of cTnT. In addition, fullerene-C60 promotes the formation of gap junction among cells. These findings have important implications for clinical application of fullerenes in the treatment of myocardial infarction.Keywords: C60, BADSCs, molecular mechanisms, myocardium

Xiao-dong Zhuang,1,* Li-zhen Liao,2,* Xiao-bian Dong,1 Xun Hu,1 Yue Guo,1 Zhi-min Du,1 Xin-xue Liao,1 Li-chun Wang1 1Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Health, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 µM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice. Keywords: curcumin, synthesis, ACE inhibition, antihypertensive, vasodilation, bioavail­ability

Jiong Chen,1,2,* Hong Xu,1,2,* Xing-Xing Zhu1,21Department of General Surgery, Affiliated Provincial Hospital, Anhui Medical University, 2Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, People’s Republic of China*These authors contributed equally tothis workAbstract: Soluble major histocompatibility complex class I-related chain A molecules (sMICA) and natural-killer group 2 member D (NKG2D) not only correlate with tumorigenesis and progression, but also with tumor invasion and metastasis. In this study, we used immunohistochemistry to investigate the correlation and prognostic significance of the differential expression of sMICA and NKG2D in pancreatic carcinoma and paracarcinoma tissues from 70 patients with pancreatic carcinomas. The results showed that sMICA expression was significantly (P

Hao Zhang,1 Xinxin Hou,2 Mei Lin,3 Ling Wang,1 Hongbo Li,4 Chenyan Yuan,1 Chen Liang,1 Jia Zhang,5 Dongsheng Zhang1,6 1Medical School of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Medical School of Henan Polytechnic University, Jiaozuo, Henan, People’s Republic of China; 3Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, People’s Republic of China; 4Department of Ultrasound in Medicine, The First Affiliated Hospital (Jiangsu Province Hospital of TCM), Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 5Jiangsu Cancer Hospital, Nanjing, Jiangsu, People’s Republic of China; 6Jiangsu Key Laboratory For Biomaterials and Devices, Nanjing, Jiangsu, People’s Republic of China Abstract: As one of the most common malignant tumors, the clinical and socio-economic consequences of lung cancer are significant. Currently, surgery is the main treatment strategy for this disease, but the survival rates of lung cancer patients are not ideal due to the high recurrence rate of the disease. Therefore, many researchers are exploring new specific therapeutic methods that are highly curative and minimally cytotoxic to healthy tissues. To this end, albumin nanospheres simultaneously were loaded with super-paramagnetic iron oxide nanoparticles (as gene vector and anticancer gene), and plasmid pDONR223-IFNG, and modified with anti-EGFR monoclonal antibody cetuximab as therapy. Targeting agents, namely gene-loaded immunomagnetic albumin nanospheres (cetuximab [C225]-IFNG-IMANS), were prepared for targeted lung carcinoma cells (GLC-82 cell lines). Transmission electron microscopy images showed that the C225-IFNG-IMANS were successfully prepared, and the ability of the nanospheres to target GLC-82 cells in vitro was confirmed by Prussian blue staining, immunofluorescence experiments, and magnetic resonance imaging. Transfection photographs and agarose gel electrophoresis proved that pDONR223-IFNG could be encased in the albumin nanospheres. A Cell Counting Kit-8 assay showed that the combination therapy group had significantly more therapeutic effects on GLC-82 cells than other therapy groups. A flow cytometry assay showed that the apoptotic index of the combined treatment group was 67.68%, whereas the indices of the C225 group, gene therapy group, and magnetic fluid hyperthermia group were 12.2%, 16.34%, and 20.04% respectively. Therefore, the combination of thermal treatment, molecular targeted treatment, and gene treatment synergistically targets GLC-82 cells, and the use of C225-IFNG-IMANS as a gene or drug carrier offers a novel and promising approach for the treatment of lung cancer. Keywords: targeting gene therapy, nano-drug, magnetic nanoparticles

OBJECTIVE: Deficits in spatial navigation are characteristic and disabling features of typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA). Visual cues have been proposed to mitigate such deficits; however, there is currently little empirical evidence for their use. METHODS: The effect of visual cues on visually guided navigation was assessed within a simplified real-world setting in individuals with tAD (n = 10), PCA (n = 8), and healthy controls (n = 12). In a repeated-measures design comprising 36 trials, participants walked to a visible target destination (an open door within a built environment), with or without the presence of an obstacle. Contrast and motion-based cues were evaluated; both aimed to facilitate performance by applying perceptual changes to target destinations without carrying explicit information. The primary outcome was completion time; secondary outcomes were measures of fixation position and walking path directness during consecutive task phases, determined using mobile eyetracking and motion capture methods. RESULTS: Results illustrate marked deficits in patients' navigational ability, with patient groups taking an estimated two to three times longer to reach target destinations than controls and exhibiting tortuous walking paths. There were no significant differences between tAD and PCA task performance. Overall, patients took less time to reach target destinations under cue conditions (contrast-cue: 11.8%; 95% CI: [2.5, 20.3]) and were more likely initially to fixate on targets. INTERPRETATION: The study evaluated navigation to destinations within a real-world environment. There is evidence that introducing perceptual changes to the environment may improve patients' navigational ability.

In the present modern era with the development of power systems, fast and accurate faults locations becoming more and more important. Power grids produce transient travelling wave signals, which transmit along the transmission line to each substation with the speed approaching the velocity of light. Using the exact arrival time of the fault traveling wave and the waveform characteristics recorded at each substation, the traveling wave based fault location and protection can be realized. The fault location has high precision, and the protection has fast action speed. So, current transformer saturation low frequency oscillation and fault resistance cannot influence it. Fault location device (FLD) is installed at each substation in power grid, and travelling wave host computer is installed in control center. When a fault occurs, FLD records the switch operation information and the arrival time of the travelling wave, the information is then transmitted to the host computer. Lightning strike fault location method can only locate the fault caused by lightning, and it hardly satisfies the operation requirements in power system. Travelling wave fault location method with GPS is simple and with high precision, it has been applied in extra-high-voltage.

Quantifying the spatiotemporal change of land cover and understanding their ecological, environmental, and socioeconomic impacts are important for sustainable development. Surface mining by the minerals industry is one driver of the changes in land cover, leading to loss of natural vegetation and top soils, and interruption of ecosystem service flows. This study investigates the effectiveness of remote sensing datasets to identify and map land cover changes, with the specific goal of understanding the impact of surface mining activities on land cover globally from 1980s to 2013. Diverse remote sensing datasets with long term observations are analyzed, including high-resolution images in Google Earth, Landsat Thematic Mapper (TM)/Enhanced Thematic Mapper Plus (ETM +)/Operational Land Imager (OLI), the Moderate Resolution Imaging Spectroradiometer (MODIS) Vegetation Index (VI) product and Defense Meteorological Satellites Program (DMSP)/Operational Linescan System (OLS) stable night-time light. The results indicated that after entering 21st century, North America (e.g., the United States and Canada) was the only continent to have more surface mining spots categorized as Shrink type (rehabilitated) rather than Expand type. South America (e.g., Chile and Brazil) and Asia (e.g., India and China) had the highest proportions of Expand Type of surface mining spots. Detailed demonstrations on how those remote sensing datasets could help in mining spot monitoring are presented.