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Additional file 1. File 1: Full inclusion and exclusion criteria. File 2: Complete dose adjustment principles.

Background Long noncoding RNAs (lncRNAs) are known as key regulators in many cancer types, but their biological functions in nasopharyngeal carcinoma (NPC) remain largely unknown. In the present study, we aim to explore the role of the lncRNA ZNRD1-AS1 in NPC tumor development. Methods The role of ZNRD1-AS1 in NPC tissues and cells was explored by using quantitative real-time PCR assay. Cellular behavioral experiments were used in testing NPC cell proliferation, invasion, and migration. Luciferase reporter assay, RNA-binding protein immunoprecipitation, and Western blot analysis were used in estimating the associations among ZNRD1-AS1, miR-335, and ROCK1. Results ZNRD1-AS1 expression was elevated in the NPC tissues and cells, and ZNRD1-AS1 overexpression was positively correlated with advanced TNM stage and the presence of lymph node metastasis. Our biological experiments indicated that ZNRD1-AS1 knockdown reduces NPC cell invasion and metastasis. Further analyses revealed that ZNRD1-AS1 as a ceRNA promotes the migration and invasion of NPC cells by sponging miR-335. We provided evidence that ZNRD1-AS1 facilitates the invasion and metastasis of NPC cells via the miR-335–ROCK1 axis. Conclusion Our data shed light on the oncogenic role of ZNRD1-AS1 in NPC tumor development, and a promising therapeutic target for NPC was identified.

Jie Chen,1,2,* Chengxian Ma,2,* Yufeng Zhang,2 Shuai Pei,1,2 Mingyu Du,2 Yujie Zhang,2 Luxi Qian,2 Jianlin Wang,2 Li Yin,2 Xia He1,2 1Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xia HeXuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaEmail hexiabm@163.com Li YinJiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, People’s Republic of ChinaEmail yinli_2012@126.comBackground: Mounting evidence has reported that microRNA-154-5p (miR-154-5p) is involved in the development of multiple cancers, but its function in nasopharyngeal carcinoma (NPC) remains not well investigated.Methods: Real-time quantitative PCR (qRT-PCR) was used to detect miR-154-5p expression in NPC tissues and cells. CCK8, colony formation, wound healing and transwell assays were performed to assess cell proliferation, migration and invasion. Dual-luciferase reporter assays and Western blots were performed to confirm the target gene of miR-154-5p. Rescue experiments were conducted to explore the influence of target gene KIF14 on the functions of miR-154-5p. Xenograft tumor model was conducted to detect the effect of miR-154-5p in vivo.Results: qRT-PCR results revealed that the expression of miR-154-5p was down-regulated in NPC tissues and cell lines compared to normal nasopharyngeal tissues and cell line. Overexpression of miR-154-5p inhibited cell migration and invasion. However, miR-154-5p had no influence on the proliferation of NPC cells. MiR-154-5p overexpression suppressed xenograft tumor metastasis in vivo. Dual-luciferase reporter analysis identified KIF14 as a target gene of miR-154-5p. Rescue experiments showed that knockdown of KIF14 reversed the effect of inhibiting miR-154-5p expression on NPC cell migration and invasion.Conclusion: Taken together, miR-154-5p suppresses tumor migration and invasion by targeting KIF14 in NPC. The newly identified miR-154-5p/KIF14 interaction offers further insights into the progression of NPC, which may represent a novel target for NPC diagnosis and treatment.Keywords: MiR-154-5p, KIF14, nasopharyngeal carcinoma, migration and invasion

Tingting Wang,1,* Mingyu Du,1,* Wenjun Zhang,1,* Hui Bai,2 Li Yin,1 Wei Chen,1 Xia He,1 Qi Chen2 1The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, People’s Republic of China; 2Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xia HeThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 42 Bai Zi Ting Road, Nanjing, Jiangsu, People’s Republic of ChinaEmail hexiabm@163.comQi ChenDepartment of Pathophysiology, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, People’s Republic of ChinaEmail qichen@njmu.edu.cnBackground: E2F transcription factor 3 (E2F3) is oncogenic and dysregulated in various malignancies. Complex networks involving microRNAs (miRNAs) and E2F3 regulate tumorigenesis and progression. However, the potential roles of E2F3 and its target miRNAs in nasopharyngeal carcinoma (NPC) are rarely reported.Methods: E2F3 expression was detected in human NPC tissues and cell lines through quantitative real-time PCR. NPC cell proliferation, migration, and invasion were evaluated in vitro by colony forming, cell counting kit-8, wound healing, and Transwell invasion assays. Publicly available database software was used to explore the target miRNAs of E2F3. Dual-luciferase reporter assay was performed to identify the direct relationship. The function of miRNAs in vivo was investigated by using a tumor xenograft model.Results: E2F3 was upregulated in NPC cell lines and tissues, and its exotic expression promoted NPC cell invasion and migration. E2F3 was identified as a target of miR-432, which restrained NPC cell invasion and migration in vitro and in vivo. Further experiments revealed that miR-432 repressed the invasion and migration potential of NPC cells by modulating E2F3 expression.Conclusion: miRNA-432 suppressed the malignant biological behavior of NPC cells by targeting E2F3. This study provided further insights into NPC prognosis and treatment.Keywords: E2F3, nasopharyngeal carcinoma, miR-432, invasion, migration

Qiang Wang,1,2,* Xinyu Hu,1,* Mingyu Du,1,* Zhiwei Lu,2 Keshi Yan,3 Dingliang Zhao,4 Ning Jiang,1 Yi Peng,1 Xia He,1 Li Yin1 1The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, People’s Republic of China; 2Department of Radiation Oncology, Xuzhou Cancer Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, Clinical Medical School of Yangzhou University, Subei People’s Hospital of Jiangsu Province, Yangzhou, People’s Republic of China; 4Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xia He; Li YinThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 42 Bai Zi Ting Road, Nanjing, Jiangsu, People’s Republic of China, Email hexiabm@163.com; yinli_2012@126.comBackground: Long noncoding RNAs (lncRNAs) are known as key regulators in many cancer types, but their biological functions in nasopharyngeal carcinoma (NPC) remain largely unknown. In the present study, we aim to explore the role of the lncRNA ZNRD1-AS1 in NPC tumor development.Methods: The role of ZNRD1-AS1 in NPC tissues and cells was explored by using quantitative real-time PCR assay. Cellular behavioral experiments were used in testing NPC cell proliferation, invasion, and migration. Luciferase reporter assay, RNA-binding protein immunoprecipitation, and Western blot analysis were used in estimating the associations among ZNRD1-AS1, miR-335, and ROCK1.Results: ZNRD1-AS1 expression was elevated in the NPC tissues and cells, and ZNRD1-AS1 overexpression was positively correlated with advanced TNM stage and the presence of lymph node metastasis. Our biological experiments indicated that ZNRD1-AS1 knockdown reduces NPC cell invasion and metastasis. Further analyses revealed that ZNRD1-AS1 as a ceRNA promotes the migration and invasion of NPC cells by sponging miR-335. We provided evidence that ZNRD1-AS1 facilitates the invasion and metastasis of NPC cells via the miR-335–ROCK1 axis.Conclusion: Our data shed light on the oncogenic role of ZNRD1-AS1 in NPC tumor development, and a promising therapeutic target for NPC was identified.Keywords: nasopharyngeal carcinoma, ZNRD1-AS1, miR-335

Recently, long non-coding RNAs (lncRNAs) have been reported as the vital regulators of various cancers including nasopharyngeal carcinoma (NPC). An increasing number of studies have suggested that lncRNA LINC01133 is dysregulated and involved in human carcinogenesis. However, the roles of LINC01133 in NPC remain largely unknown. In this work, we demonstrated that LINC01133 was significantly downregulated in NPC tissues and cell lines. Loss and gain of function experiments provided evidence that LINC01133 inhibited NPC cell proliferation, invasion and migration both in vitro and in vivo. Besides, Fluorescence in situ hybridization (FISH) assay was performed to determine the localization of LINC01133 and LINC01133 was observed mainly distributed in the nucleus. Importantly, RNA pull-down and RIP assays showed that LINC01133 directly combined with YBX1, and YBX1 can partly reverse the repression of NPC cell proliferation, migration, and invasion caused by LINC01133. Collectively, our exploration indicate that LINC01133 inhibits the malignant-biological behavior of NPC cells by binding to YBX1, thereby suggesting a novel biomarker for the NPC prognosis and treatment.

OBJECTIVE: To assess the effectiveness of a three-stage intervention to reduce caesarean deliveries in a Chinese tertiary hospital. METHODS: A retrospective study was conducted to assess whether educating staff, educating patients and auditing surgeon practices (introduced in 2005) had reduced caesarean delivery rates. Multiple logistic regression was used to check for a potential association between caesarean rates and rates of admission to the neonatal intensive care unit (NICU). FINDINGS: The caesarean delivery rate ranged from 53.5% to 56.1% in 2001-2004 and from 43.9% to 36.1% in 2005-2011. When 2001-2004 and 2005-2011 were treated as "before" and "after" periods to evaluate the intervention's impact on the mean caesarean section rate, a significant reduction was noted: from 54.8% to 40.3% (odds ratio, OR: 0.56; 95% confidence interval, CI: 0.52-0.59; χ2 test: P < 0.001). The overall drop in the caesarean section rate was significant (χ2 test: P < 0.001) and inversely correlated with the years (Spearman's ρ: -0.096; P < 0.001). Although complicated pregnancies increased after 2004, the primary caesarean section rate decreased annually by 20% on average in 2005-2011, after practice audits were implemented. Multiple logistic regression showed a positive association between the caesarean delivery rate and the rate of admission to the NICU (adjusted OR: 1.26; 95% CI: 1.14-1.40). CONCLUSION: Patient and staff education and practice audits reduced the Caesarean section rate in a tertiary referral hospital without an increase in admissions to the NICU.

A new type of air-driven multi-fingered dexterous hand, named ZJUT Hand, is proposed. ZJUT Hand has good passive flexibility and can make up for the deficiency of existing dexterous hands in some ways. A new method for grasping model identification based ANFIS is proposed. Simulation experimental results show that the method can easily establish the model of the target objects, and has very good recognition accuracy and convergence. Equivalent rules of target objects are presented and greatly improve the efficiency of identification. A general grasp planning program of multi-fingered dexterous hand is proposed. Finally, the grasp planning experiments for ZJUT Hand is completed. Experimental results show that ZJUT Hand is able to construct the models of two typical target objects.

A generalized predictive control strategy aimed at a kind of bilinear Hammerstein model is proposed in the paper. The strategy avoids solving the high level equation by improving the static nonlinearity portion in the bilinear Hammerstein model and adopts the generalized predictive control algorithm in the bilinear portion to avoid the heavy computation of generic nonlinear optimization, thus the middle variable has an analytical form. The ability to resist disturbance is enhanced due to the introduction of multi-step generalized predictions control. Simulation examples demonstrate the effectiveness of the strategy.