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Zhongjing Lv,1,2,* Kun Wu,1,3,* Xing Qin,1,3 Jian Yuan,2 Ming Yan,1,3 Jianjun Zhang,1,3 Lizhen Wang,1,4 Tong Ji,1,3 Wei Cao,1,3 Wantao Chen1,3 1Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Stomatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, People’s Republic of China; 3Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, People’s Republic of China; 4Department of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wantao Chen; Wei CaoDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Key Laboratory of Stomatology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaEmail chenwantao2002@hotmail.com; caowei561521@hotmail.comBackground: In our previous study, serine protease inhibitor Kazal-type 5 (SPINK5), which encodes the product of serine protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) was found to be down-regulated in head and neck squamous cell carcinoma (HNSCC) using oligonucleotide microarrays. However, the function and clinical implications of SPINK5/LEKTI remain obscure in HNSCC.Methods: The endogenous expression level of SPINK5/LEKTI was further verified in 9 HNSCC cell lines and HNSCCs by means of reverse transcription-polymerase chain reaction, real-time PCR, Western blotting and immunohistochemistry. The biological function of SPINK5/LEKTI was investigated in vitro and in vivo experiments. Kaplan–Meier survival analysis and Cox proportional hazards regression model were used to determine the correlation between SPINK5/LEKTI expression and clinical outcome.Results: Down-regulation expression of SPINK5/LEKTI was found in six out of nine HNSCC cell lines and in 85.7% HNSCC specimens (P< 0.0001). Upon silencing of SPINK5/LEKTI, the cell proliferation, plate colony formation and cell invasion of WU-HN6 cells were significantly increased, while exogenous overexpression of SPINK5/LEKTI, the proliferation, plate colony and invasion of WU-HN13 and HN30 cells were remarkably inhibited with the arrest of G1 cell cycle (P=0.0001, P=0.003, respectively). HNSCC patients with lower LEKTI levels had significantly inferior overall survival compared to those patients with higher LEKTI (P=0.0017) by Kaplan–Meier survival analysis. Univariate and multivariate Cox proportional hazards regression model analysis revealed that LEKTI expression was an independent prognostic predictor for HNSCC patients (HR=0.114, 95% CI:0.044– 0.292, P< 0.001).Conclusion: Our results demonstrate that SPINK5/LEKTI might be a tumor suppressor in HNSCCs and serve as an independent prognostic predictor for HNSCC patients.Keywords: SPINK5/LEKTI, biological function, head and neck squamous cell carcinoma, prognostic predictor

Kun Wu,1 Zhu Yu,1 Zhenyong Tang,1 Weiyuan Wei,1 Dongyi Xie,1 Yubo Xie,2 Qiang Xiao1 1Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Yubo Xie; Qiang XiaoDepartment of Anesthesiology, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel/Fax +86 771 535 8325Email 1157817791@qq.com; xiaoqiang@gxmu.edu.cnPurpose: miR-877-5p has been reported as a tumor suppressor in multiple cancers. Its role in gastric cancer, however, remains unclear. Hence, the purpose of this study was to elucidate the function, and underlying molecular mechanism, of miR-877-5p in the development of gastric cancer.Materials and Methods: We first analyzed miR-877-5p expression using the Gene Expression Omnibus (GEO) database and detected its expression in gastric cancer and gastric epithelial cells via real-time quantitative PCR (qRT-PCR). We then assessed the role of miR-877-5p in gastric cancer proliferation, apoptosis, and cell cycling. The gene targeted by miR-877-5p was predicted by bioinformatic analysis and confirmed by dual luciferase assay. Subsequently, rescue assays were carried out to validate whether the miR-877-5p effects on gastric cancer growth are dependent on the proposed target gene.Results: miR-877-5p levels were lower in gastric cancer than in controls, based on the GEO and qRT-PCR analyses. Overexpression of miR-877-5p significantly inhibited cell growth and cell cycle progression, whereas it promoted apoptosis. Furthermore, forkhead box M1 (FOXM1) was predicted as a target of miR-877-5p, the overexpression of which diminished the suppressive effect that upregulation of miR-877-5p had on gastric cancer cells.Conclusion: Our study results indicate that the miR-877-5p/FOXM1 axis plays an important role in gastric cancer progression, while suggesting miR-877-5p as a novel potential therapeutic target for gastric cancer.Keywords: gastric carcinoma, microRNA-877-5p, forkhead box M1, tumor growth, cell cycle arrest, tumor suppressor function

Yaping Xu,1,2 Yihao Huang,1 Wanqiong Xu,1 Xiaohui Zheng,1 Xue Yi,1,2 Liyue Huang,1 Yuxiao Wang,1 Kangni Wu3 1Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Department of Physiology, Xiamen Medical College, Xiamen 361023, People’s Republic of China; 2Xiamen Key Laboratory of Respiratory Diseases, Xiamen 361023, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, Medical College of Xiamen University, Xiamen 361003, People’s Republic of ChinaCorrespondence: Yaping Xu; Kangni Wu Tel +86-159 5923 5683Email ypxu@xmmc.edu.cn; wukangni20818063@zju.edu.cnObjective: Hepatic stellate cells (HSCs) are the important players in liver cirrhosis and liver cancer. They also act as critical mediators of immunosuppression in hepatocellular carcinoma (HCC). In this study, we hypothesized that HSCs promote HCC progression via C3.Methods: C3 in HSCs was knocked down using a shRNA retroviral plasmid. The conditioned medium from HSCs or shC3 HSCs (knockdown of C3 by shRNA in HSCs) was collected to detect their effects on bone marrow (BM) and T cells (including expansion and apoptosis) in vitro, and in an HCC in situ model in mice.Results: We found that HSCs promoted T-cell apoptosis and decreased their proliferation, inhibited dendritic cell (DC) maturation, and induced myeloid-derived suppressor cell (MDSC) expansion through the C3 pathway in vitro. In addition, the knockdown of C3 suppressed HSC-promoted HCC development in the orthotopic transplantation tumor model of HCC in mice.Conclusion: These findings provide more insights into the immunomodulatory roles of HSCs in HCC progression and indicate that modulation of the C3 pathway might be a novel therapeutic approach for liver cancer.Keywords: hepatocellular carcinoma, hepatic stellate cells, complement C3, myeloid-derived suppressor cells, T cells

Xing-Ru Zhang, 1,* Zhi-Yu Jiang, 2,* Zeng-Rui Zhang, 3 Hui-Jun Chen, 1 Ke Wu, 4 Jin-Cai He, 1 Cheng-Long Xie 1 1The Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 2The Department of General Surgery, The Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou 310000, People’s Republic of China; 3Department of Neurology, Huzhou Central Hospital, Huzhou 313000, People’s Republic of China; 4Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng-Long Xie; Jin-Cai He Tel/Fax +86 577 88 83 2693Email cl_xie1987@sohu.com; hjc@wmu.edu.cnBackground: Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson’s disease (PD) patients and effectively reduces poor mobility and dyskinesia.Methods: Electronic databases were searched up to January 1, 2018. The inclusion criteria for this review were as follows: LCIG vs oral medication in advanced PD patients.Results: Five trials, with a total of 198 patients, met all the inclusion criteria. The quality score of these studies ranged from 3 to 5. Two clinical trials showed that compared with oral medication, LCIG had a better treatment effect on on-time with troublesome dyskinesia (TSD) (p = 0.02) and on-time without TSD (p < 0.00001) in advanced PD patients. In addition, four of the 5 studies showed that the LCIG may have better efficacy than oral medication for improving the scores of the UPDRS, and two studies found that LCIG demonstrated better efficacy for improving the PDQ-39 scores. The video recording results indicated a potential decline in both dyskinesia and the “off” state in LCIG-treated patients. The incidence of adverse events was not significantly different between the LCIG and oral medication groups.Conclusion: Compared with oral treatment, LCIG exerts its effectiveness, mostly by reducing the time of on-time with TSD, increasing the time of on-time without TSD and scores of UPDRS and PDQ-39. It is suggesting that LCIG was likely to be a new type of administration used in clinical applications. However, due to methodological flaws, these findings should be viewed with caution, and more RCTs are needed in the field to complement our findings.Keywords: Levodopa-carbidopa intestinal gel, Parkinson’s disease, oral medication, clinical trials, systematic review

In this work, we present an atomic-scale investigation of L10-FePt particles that are partly or fully embedded in a single-crystalline MgO matrix. Hundreds of particles in different orientations, of different sizes, and with different side contact facets are statistically and quantitatively analyzed. It is found that the presence of side contact facets does not introduce any misorientation in particles with the c axis out-of-plane (OP), even in those of small sizes. In addition, a markedly higher proportion of in-plane (IP) variants is found in smaller particles of sizes less than 10 nm, and most IP variants and the IP part in multi-variants have a large area of side contact facets or are even fully embedded. Those results can be explained by the fact that the transformation strain and interface strain jointly affect the particle orientation, and the competition between total strain energy in the film plane and in lateral planes plays a key role in determining particle orientation. Thus, a suggestion on the L10-FePt nanoparticle film production can be proposed that a moderate area of side contact facets may help keep a perfect OP orientation in the OP particles without increasing the proportion of IP variants. Additionally, our work can provide reference information on the variant orientation preference during a post-annealing process in nanoparticle films on a rough substrate or embedded in a matrix as well as in core–shell material systems. [ABSTRACT FROM AUTHOR]

Xianguang Bai,1,2,* Ming Yi,2,* Ying Jiao,2 Qian Chu,2 Kongming Wu2,3 1Medical School, Pingdingshan University, Pingdingshan, Henan, People’s Republic of China; 2Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kongming Wu; Qian ChuDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of ChinaEmail kmwu@tjh.tjmu.edu.cn; qianchu@tjh.tjmu.edu.cnAbstract: During malignant transformation, a growing body of mutations accumulate in cancer cells which not only drive cancer progression but also endow cancer cells with high immunogenicity. However, because one or multiple steps in cancer-immunity cycle are impaired, anti-cancer immune response is too weak to effectively clear cancer cells. Therefore, how to restore robust immune response to malignant cells is a hot research topic in cancer therapeutics field. In the last decade, based on the deeper understanding of cancer immunity, great signs of progress have been made in cancer immunotherapies especially immune checkpoint inhibitors (ICIs). ICIs could block negative immune co-stimulatory pathways and reactivate tumor-infiltrating lymphocytes (TILs) from exhausted status. ICIs exhibit potent anti-cancer effect and have been approved for the treatment of numerous cancer types. Parallel with durable and effective tumor control, the actual response rate of ICIs is unsatisfactory. Although a subset of patients benefit from ICIs treatment, a large proportion of patients show primary or acquired resistance. Previously intensive studies indicated that the efficacy of ICIs was determined by a series of factors including tumor mutation burden, programmed death ligand-1 (PD-L1) expression, and TILs status. Recently, it was reported that transforming growth factor-beta (TGF-β) signaling pathway participated in cancer immune escape and ICI resistance. Concurrent TGF-β blockade might be a feasible strategy to enhance the efficacy of immunotherapy and relieve ICI resistance. In this mini-review, we summarized the latest understanding of TGF-β signaling pathway and cancer immunity. Besides, we highlighted the synergistic effect of TGF-β blockade and ICIs.Keywords: immunotherapy, immune checkpoint inhibitor, PD-1, PD-L1, TGF-β, tumor immune microenvironment, tumor infiltrating lymphocyte

Research has shown that there are significant gaps in hepatitis B knowledge among migrant communities who are at risk of hepatitis B, such as Chinese and Vietnamese communities. Many students studying within Australia come from countries with high prevalence of hepatitis B. However, there is very little research examining hepatitis B knowledge, screening, or vaccination among university students in Australia or worldwide. The aim of this paper was to measure both levels of and demographic differences in hepatitis B screening and knowledge among Chinese and Vietnamese students in Australia. Online surveys were completed by 112 Chinese- and 95 Vietnamese-identifying students in Australia, measuring knowledge of hepatitis B, engagement in screening and vaccination, and demographic characteristics. Results show that although engagement in screening and vaccination for hepatitis B was high, there were significant gaps in knowledge around transmission of hepatitis B. There were also some key demographic differences in screening and knowledge. For instance, those born in Australia were more likely to have been screened compared to those born Mainland China, Hong Kong, or Vietnam. Chinese students born in Australia had lower levels of knowledge compared to those born in Mainland China or Hong Kong. Among both samples, knowing someone living with hepatitis B was associated with higher levels of knowledge. Findings underscore the need for education-based interventions to address the significant gaps that exist in knowledge around hepatitis B, with a specific need for culturally appropriate resources in a range of languages to cater to the diverse communities who may be at risk of hepatitis B. [ABSTRACT FROM AUTHOR]

Wei Zhou,1,2,* Jiachun Weng,1,* Keyan Wu,1,2,* Xiao Xu,1,* Hui Wang,1,* Jing Zhang,3,* Chengxue Zhao,1 Jie Yang,1 Yu Zhang,1,4,5 Weigan Shen1,4,5 1Department of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, People’s Republic of China; 2Department of Internal Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Internal Medicine, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, People’s Republic of China; 4Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People’s Republic of China; 5Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Zhang; Weigan ShenDepartment of Cell Biology, School of Medicine of Yangzhou University, No. 136 Middle Jiangyang Street, Yangzhou 225009, Jiangsu, People’s Republic of ChinaTel +86 05 148 797 8875Fax +86 05 148 734 1733Email yzzy10182001@aliyun.com; shenweigan@hotmail.comPurpose: The aim of the present study was to investigate the effect of knockdown and knockout of the transcriptional co-activator with PDZ-binding motif (TAZ) on the migration, invasion and autophagy of the hepatocellular carcinoma (HCC) cell lines, as well as the functional connection between the autophagy and cell migratory processes induced by loss of TAZ in HCC cell lines.Methods: HCC cell lines SMMC-7721 and SK-HEP1 stably knockdown and knockout of TAZ were established by the lentiviral-mediated TAZ knockdown and knockout approaches. Reverse transcription-quantitative real-time polymerase chain reaction and Western blotting were performed to examine the expression of TAZ and indicated genes in downstream pathways in HCC cell lines. Transwell assay and autophagic flux assay were used to evaluate the effect of TAZ knockdown and knockout on the motility and the autophagy of HCC cell lines.Results: We initially found that TAZ exhibited highly abundant and was expressed predominantly in HCC cell lines with different spontaneous metastatic potential. Through performing loss-of-function assays, we demonstrated that both TAZ knockdown and knockout promoted HCC cell autophagy and reduced HCC cell migration, invasion and epithelial-to-mesenchymal transition. In addition, autophagy inhibition in TAZ knockdown and knockout SMMC-7721 and SK-HEP1 cells in the presence of 3-methyladenine or chloroquine partially abrogated the migratory and invasive ability induced by TAZ knockdown and knockout.Conclusion: Our findings indicated that loss of TAZ in HCC cells suppressed cell motility probably via altering the autophagy, suggesting that TAZ emerges as an important target in regulating cell motility and autophagy in HCC cells, and blocking TAZ may be a novel therapeutic strategy against HCC.Keywords: TAZ, autophagy, migration, invasion, hepatocellular carcinoma

Xinhua Wu,1 Tao Yu,1 Ning Ji,1 Yujie Huang,1 Lingcheng Gao,1 Wen Shi,1 Yan Yan,1 Hang Li,1 Liming Ma,1 Kede Wu,2 Zhen Wu31Department of Endocrinology, Huaian Hospital of Huaian District, Huaian, Jiangsu 223200, People’s Republic of China; 2Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu 225009, People’s Republic of China; 3Electric Engineering, China University of Mining and Technology, Xuzhou, Jiangsu 221116, People’s Republic of ChinaCorrespondence: Xinhua WuDepartment of Endocrinology, Huaian Hospital of Huaian District, 50 Meters North of Huaihe Road, Huaian 223200, People’s Republic of ChinaTel +865 178 593 9208Email wuxh8686@163.comBackground and aim: Type 2 diabetes mellitus (T2DM) is a common disease of harming to people’s health. MicroRNAs have recently been considered as key regulators of many biological processes, such as cell proliferation, migration and apoptosis. However, the effect of miR-22 expression by targeting IL6 receptor (IL6R) in T2DM and potential molecular mechanism involved remains to be elucidated. The present study aimed to explore the regulatory mechanism of miR-22 by targeting IL6R in pancreatic beta-cells viability and apoptosis of T2DM.Methods: The expressions of miR-22, IL6R and apolipoprotein (apoA1, apoB and apoE) were examined by reverse transcription-quantitative PCR (qRT-PCR). Pancreatic beta-cells were transiently transfected with a miR-22 mimic or si-IL6R plasmid which validated with qRT-PCR to analyze the expression of miR-22 or IL6R. Cell viability, apoptosis and protein expression levels were determined by CCK-8, flow cytometry and Western blotting, respectively.Results: The proportion of INS-1E cell apoptosis was increased in islets of diabetic rats. Furthermore, miR-22 was downregulated and IL6R was upregulated in both diabetic serum and glucose-induced INS-1E cells. miR-22 overexpression or IL6R inhibition significantly strengthened cell viability and reduced the expression of apoptosis-related proteins to suppress cell apoptosis. IL6R was demonstrated as a target gene of miR-22 which could negatively regulate IL6R expression. Moreover, phosphorylation of JAK/STAT signaling pathway was activated by miR-22 overexpression or IL6R inhibition to strengthen the viability and suppress apoptosis of INS-1E cells.Conclusion: This study indicated that miR-22 strengthened the viability and suppressed apoptosis of INS-1E cells, partly by down-regulation of IL6R through the activation of JAK/STAT signaling pathway.Keywords: IL6R, pancreatic beta-cells, type 2 diabetes mellitus, JAK/STAT signaling pathway, miR-22

Qingyi Zhang,1,* Xuan Zhao,2,* Chaoqi Zhang,3 Wei Wang,4 Feng Li,5 Donglei Liu,1 Kai Wu,1 Dengyan Zhu,1 Shasha Liu,2 Chunyi Shen,2 Xin Yuan,6 Kai Zhang,2 Yang Yang,1 Yi Zhang,2 Song Zhao1,71Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan Province 450052, People’s Republic of China; 2Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China; 3Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 4Henan Medical Association, Zhengzhou, Henan Province 450000, People’s Republic of China; 5Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Berlin 10117, Germany; 6Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Henan Province 450052, People’s Republic of China; 7Key Laboratory of Thoracic Tumor of Zhengzhou City, Zhengzhou, Henan 450052, People’s Republic of ChinaCorrespondence: Song ZhaoDepartment of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan province 450052, People’s Republic of ChinaTel +86 1 367 366 5008Email 13673665008@163.comYi ZhangBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of ChinaTel +86 1 513 892 8971Email yizhang@zzu.edu.cn*These authors contributed equally to this workBackground: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide and the 5-year overall survival rate remains poor. Protein kinase, membrane associated tyrosine/threonine (PKMYT1) is overexpressed in several cancers and participate in tumor progression. However, the mechanism of PKMYT1 in ESCC is unclear.Purpose: The objective of our study was to demonstrate the the expression and role of PKMYT1 in ESCC.Patients and methods: We detected the expression of PKMYT1 in ESCC patients and analysed the correlation with overall survival time and disease-free survival time. Then we detected PKMYT1 expression in ESCC cell lines and immortalized human esophageal epithelial cell line. Down-regulated PKMYT1 was carried out in KYSE70 and KYSE450 cells to invetigate the mechanism of PKMYT1 in ESCC cells.Results: PKMYT1 was up-regulated in tumor tissues and ESCC cell lines, and higher expression of PKMYT1 correlated with poorer overall survival in ESCC patients. Besides, in ESCC cell lines KYSE70 and KYSE450, knocking down PKMYT1 allowed more cells to skip G2/M checkpoint to complete mitosis, which promoted cell apoptosis, inhibited cell proliferation, and prevented the EMT phenotype in vitro. Meantime, we also observed that down-regulated PKMYT1 in ESCC cells suppressed AKT/mTOR signaling pathway. These results demonstrated PKMYT1 may act as an oncogene in ESCC.Conclusion: PKMYT1 plays an crutial role in ESCC progression, downregulated PKMYT1 might inhibit the development of ESCC by AKT/mTOR signaling pathway, and might be a novel target in the treatment of ESCC.Keywords: ESCC, PKMYT1, AKT, EMT, cell apoptosis

Jing Zhang,1 Kai Wu,2 Ting Xu,3 Jiajun Wu,1 Pengfei Li,1 Hong Wang,4 Huiling Wu,1 Gang Wu5 1Department of Plastic and Aesthetic Center, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China; 2Spine Lab, Department of Orthopedic Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China; 3Department of Stomatology, First Affiliated Hospital, Zhejiang University, Hangzhou, China; 4Department of Oral and Maxillofacial Surgery, Amsterdam University Medical Centre, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, North Holland, the Netherlands; 5Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, North Holland, the Netherlands Purpose: The aim of this study is to investigate the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol extracted from green tea, on the osteoblastogenic differentiation of human adipose-derived stem cells (hASCs).Patients and methods: hASCs were acquired from human adipose tissue. With informed consent, subcutaneous adipose tissue samples were harvested from periorbital fat pad resections from ten healthy female adults who underwent double eyelid surgery. hASCs were cultured in osteogenic medium with or without EGCG (1 µM, 5 µM, or 10 µM) for 14 days. We evaluated the effects of EGCG by quantifying cell growth, ALP activity (an early osteoblastogenic differentiation marker), BSP, OCN (a late osteoblastogenic differentiation marker), and extracellular matrix mineralization. We also performed Western blots to measure osteoblastogenesis-related proteins such as Runx2 and adipoblastogenesis-related transcription factors, such as STAT3, C/EBP-α, and PPAR-γ.Results: EGCG at 5 µM resulted in significantly higher cell proliferation and ALP activity than did the control on days 3, 7, and 14. On day 7, 5 µM EGCG significantly enhanced BSP expression. On day 14, EGCG at all concentrations promoted OCN expression. In addition, EGCG at 5 µM resulted in the highest level of extracellular matrix mineralization. On day 3, the expression levels of Runx2 were significantly higher in the 5 µM EGCG group than in the other groups, whereas later, on days 7 and 14, Runx2 expression levels in the EGCG group were significantly lower than those of the control group. EGCG at all three concentrations was associated with significantly lower levels of phosphorylated STAT3, C/EBP-α, and PPAR-γ.Conclusion: EGCG at 5 µM significantly enhanced the osteoblastogenic differentiation of hASCs. Keywords: EGCG, hASCs, osteoblastogenesis, STAT3, bone regeneration

To understand whether Chinese fir (Cunninghamia lanceolata) can conserve energy by reducing root volatiles to maintain growth under low phosphorus (P) conditions, we cultivated two half-sib families of Chinese fir that display high and low P use efficiency under conditions of normal P supply and total P deficiency. Gas chromatography-mass spectrometry analysis was used to determine the content of root volatiles, and the relationships among root volatiles and root growth index, P content, and distribution were analyzed. There were significantly fewer volatile organic compounds (VOCs) in the rhizosphere of these two fir families, No. 25 and No. 32, under P deficiency. Low P supply significantly promoted root growth in No. 25, increasing both average diameter and volume. A negative correlation was found between the volatiles and the increment of root average diameter and surface area. The belowground P distribution and the root to shoot P concentration (Pr/Ps) were higher in No. 25 than in No. 32. The total amount of VOCs, as well as the amount of 18 individual volatiles were positively correlated with P accumulation, aboveground P distribution, and belowground P distribution, but the opposite pattern was seen in Pr/Ps for family No. 25 seedlings. We conclude that the content and types of VOCs differ among the Chinese fir genotypes. Under low-P stress, the roots of Chinese fir reduce the release of VOCs to maintain seedling growth.

Qin Wang,1,2 Yehai Liu,1 Kaile Wu,1 Yi Zhao,1 Chaobing Gao,1 Busheng Tong,1 Ming Zhang3,4 1Department of Otolaryngology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Otolaryngology, Hefei Second People’s Hospital, Hefei, People’s Republic of China; 3Department of Anatomy, Anhui Medical University, Hefei, People’s Republic of China; 4Department of Anatomy, University of Otago, Dunedin, New ZealandObjective: To retrospectively investigate the clinical efficacy and larynx preservation of two different treatments: radiotherapy followed by surgery (R+S) and surgery followed by radiotherapy (S+R), in elderly patients with medial wall pyriform sinus cancer.Materials and methods: Medical records from 48 patients over 70 years old with medial wall pyriform sinus cancer who underwent different treatments between 2001 and 2010 were analyzed. Twenty-one patients underwent radiotherapy first followed by surgery (R+S), and the other 27 patients underwent surgery first followed by radiotherapy (S+R). A Kaplan–Meier method was used to calculate the survival rate.Results: Overall 3-year and 5-year survival rates were 60.4% and 35.4%, respectively. The 5-year survival rates in R+S group and S+R group were 38.1% and 33.3%, respectively, without a statistically significant difference between the two groups (P>0.05). Also, comparisons of the decannulation rates (64.3% for R+S group vs 50.0% for S+R group) and postoperative complication rates (42.9% for R+S group vs 37.0% for S+R group) between the two groups of patients did not show obvious differences. However, the laryngeal preservation rates in R+S group and S+R group were 66.7% and 37.0%, respectively, with significantly statistical difference between the two groups (P

Fengchun Wu,1,2,* Yue Zhang,2,3,* Yongzhe Yang,2–4 Xiaobing Lu,1,2 Ziyan Fang,1 Jianwei Huang,1 Lingyin Kong,3 Jun Chen,5,6 Yuping Ning,1,2 Xiaobo Li,7,8 Kai Wu2,3,5,6,9 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China; 2Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; 3Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (SCUT), Guangzhou, China; 4School of Medicine, South China University of Technology (SCUT), Guangzhou, China; 5Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou, China; 6National Engineering Research Center for Healthcare Devices, Guangzhou, China; 7Department of Biomedical Engineering, New Jersey Institute of Technology, NJ, USA; 8Department of Electric and Computer Engineering, New Jersey Institute of Technology, NJ, USA; 9Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan *These authors contributed equally to this work Background: Structural and functional brain abnormalities in schizophrenia (SZ) have been widely reported. However, a few studies have investigated both structural and functional characteristics in SZ patients at different stages to understand the neuropathology of SZ. Methods: In this study, we recruited 44 first-episode drug-naive SZ (FESZ) patients, 44 medicated chronic SZ (CSZ) patients, and 56 normal controls (NCs) and acquired their structural and resting-state functional magnetic resonance imaging (MRI). We then made group comparisons on structural and functional characteristics, including regional gray matter volume (GMV), regional homogeneity, amplitude of low-frequency fluctuation, and degree centrality. A linear support vector machine (SVM) combined with a recursive feature elimination (RFE) algorithm was implemented to discriminate three groups.Results: Our results indicated that the regional GMV was significantly decreased in patients compared with that in NCs; CSZ patients have more diffused GMV decreases primarily involved in the frontal and temporal lobes when compared with FESZ patients. Both FESZ and CSZ patients showed significant functional alterations compared with NCs; when compared with FESZ patients, CSZ patients showed significant reductions in functional characteristics in several brain regions associated with auditory, visual processing, and sensorimotor functions. Moreover, a linear SVM combined with a RFE algorithm was implemented to discriminate three groups. The accuracies of the three classifiers were 79.80%, 83.16%, and 81.71%, respectively. The performance of classifiers in this study with multimodal MRI was better than that of previous discriminative analyses of SZ patients with single-modal MRI.Conclusion: Our findings bring new insights into the understanding of the neuropathology of SZ and contribute to stage-specific biomarkers in diagnosis and interventions of SZ. Keywords: multimodal MRI, schizophrenia, support vector machine, SVM, classification

Xinhua Zheng,1,2,* Qian Liu,2,* Ming Yi,2 Shuang Qin,2 Kongming Wu2 1Department of Clinical Medicine, Medical School of Pingdingshan University, Pingdingshan, Henan 467000, China; 2Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China *These authors contributed equally to this work Abstract: Tumor environment plays a pivotal role in determining cancer biology characteristics. Cytokine factors, as a critical component in tumor milieu, execute distinct functions in the process of tumorigenesis and progression via the autocrine or paracrine manner. The retinal determination gene network (RDGN), which mainly comprised DACH, SIX, and EYA family members, is required for the organ development in mammalian species. While the aberrant expression of RDGN is involved in the proliferation, apoptosis, angiogenesis, and metastasis of tumors via interacting with different cytokine-related signals, such as CXCL8, IL-6, TGF-β, FGF, and VEGF, in a cell- or tissue-dependent manner. Thus, joint detection of this pathway might be used as a potential biomarker for the stratification of target therapy and for the precision prediction of the prognosis of cancer patients. Keywords: DACH1, SIX1, EYA1, cytokine, tumor, proliferation, metastasis

Yanhong Huang,1 Haiyun Xu,1 William Au,2,3 Chongtao Xu,1 Kusheng Wu2 1Mental Health Center, Shantou University Medical College, Shantou, People’s Republic of China; 2Department of Preventive Medicine, Shantou University Medical College, Shantou, People’s Republic of China; 3Institute of Advanced Studies, University of Medicine and Pharmacy, Tirgu Mures, Romania Background: The objective of this study was to investigate relationships among family environmental characteristics, behavior problems, and social function impairments in children with ADHD. Methods: Among children from four primary schools in Shantou city of China, 132 who were diagnosed with ADHD were selected and 138 typically developing children were recruited from the same schools. These children were evaluated using the self-designed questionnaire, FES-CV, CPRS, CTRS, and WFIRS-P for familial environment, behavioral problems, and social function impairment measures. In addition, children’s behavioral problems and functional impairments were evaluated using self-established field behavior observation method. Logistic regression model was used to estimate ORs and 95% CIs for ADHD risk with family environmental factors. Results: In the unconditional logistic model, ADHD risk in children was increased with parents’ worse educational level, occupational status, and emotional stability with trend. Children with ADHD had lower scores on most subscales of FES-CV (P

Han Yu,1,* Weiyuan Wei,1,2,* Wenlong Cao,1 Zexu Zhan,1 Linhai Yan,2 Kun Wu,1 Dongyi Xie,1 Bin Cai,1 Yubo Xie,3 Qiang Xiao1 1Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; 2Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; 3Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China *These authors contributed equally to this work Background: MicroRNA (miRNA) array analysis has reported that the expression of miR-593-5p is associated with lymph node metastasis in gastric cancer (GC); however, the function and mechanism of miR-593-5p in GC have not been described yet. miR-593-5p has also not been elucidated widely in other cancers. Methods: miR-593-5p expression was detected by quantitative RT-PCR (qRT-PCR) in human GC tissues and cell lines. Cell proliferation was investigated using CCK-8 assays, cell cycle was detected by flow cytometric method, and cell migration and invasion abilities were evaluated by wound-healing and transwell assays. miR-593-5p-influenced gene expression profiles were detected by total gene expression chip method in MGC-803 cells, and miR-593-5p candidate target genes were predicted using bioinformatics methods. The candidate target gene and downstream of miR-593-5p were determined by qRT-PCR, Western blot, and dual-luciferase reporter assays. The effects of miR-593-5p on the growth and metastasis of GC were evaluated by tumor xenograft experiment in vivo. Results: miR-593-5p was frequently downregulated in GC patients and GC cell lines. miR-593-5p was significantly correlated with tumor size and distant metastasis in GC patients. miR-593-5p inhibited cell proliferation, migration, and invasion and also arrested cell cycle at the G0/G1 phase in SGC-7901 and MGC-803 cells in vitro. miR-593-5p also suppressed tumor growth and metastasis in vivo. miR-593-5p influenced gene expression profile in MGC-803 cells. MST4 was indirectly targeted by miR-593-5p. miR-593-5p also downregulated FAK, MMP12, and JUN protein expression. Conclusion: Our study suggests that miR-593-5p may function as a tumor suppressor in GC through a mechanism that regulates JUN pathway via indirectly targeting the MST4 gene. Keywords: miR-593-5p, gastric cancer, MST4, JUN pathway

Yu-Tuan Wu,1,* Zhou Xu,1,* Ke Zhang,2,* Jiu-song Wu,3,* Xin Li,1,* Bilal Arshad,1 Ying-Cun Li,3 Zhong-Liang Wang,2 Hong-Yuan Li,1 Kai-Nan Wu,1 Ling-Quan Kong1 1Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; 2Department of Orthopedics, Children’s Hospital of Chongqing Medical University, Chongqing 400020, China; 3Department of General Surgery, Children’s Hospital of Chongqing Medical University, Chongqing 400020, China *These authors contributed equally to this work Abstract: The concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy (NAC) has been proposed to improve the pathologic complete response (pCR) rate, although there are conflicting views about its efficacy and safety. The purpose of this study was to evaluate the efficacy and cardiac safety of the concurrent use of trastuzumab and anthracycline-based NAC for human epidermal growth factor receptor 2 (HER2)-positive locally advanced breast cancer. We systematically searched PubMed, Embase, and Cochrane databases from inception until July 1, 2017, for relevant articles. A total of 13 studies were included in the meta-analysis. The results showed that the pCR rate was significantly higher in the concurrent use of trastuzumab and anthracycline group (45%) than that in the nonconcurrent use group (32%) (OR: 2.36, 95% CI: 1.69–3.30, P10% (OR: 1.26, 95% CI: 0.55–2.88, P=0.59), and in terms of cardiac failure (OR: 2.17, 95% CI: 0.24–19.84, P=0.49), when comparing the concurrent use of trastuzumab and anthracyclines with their nonconcurrent use. In conclusion, the concurrent use of trastuzumab and anthracycline-based NAC for certain HER2-positive locally advanced breast cancers significantly improves the pCR rates without obvious increases in the cardiotoxicity. Keywords: breast cancer, HER2, neoadjuvant chemotherapy, trastuzumab, anthracycline