High-level Universities Research Articles

Association between Use of Aspirin and Risk of Lung Cancer: Results from Pooled Cohorts and Mendelian Randomization Analyses

Background: Massive studies have examined associations between use of aspirin and lung cancer risk. However, findings from previous studies are inconsistent and it remains unclear whether there is a causality between them. Thus, we conducted a meta-analysis and further carried out Mendelian randomization (MR) analyses to elucidate the associations between aspirin use with lung cancer risk. Methods: Eligible studies were identified by searching the PubMed and several databases up to November 2019. Cohort studies, nested case-control studies, and randomized controlled trials (RCTs) investigating the impact of aspirin exposure and lung cancer were included. Relative risk (RR) were evaluated for lung cancer risk. Subgroup analyses regarding gender, pathologic subtypes and smoking status were also executed. MR analyses were conducted using statistics obtained from Neale Lab and International Lung Cancer Consortium (ILCCO) to assess the possible causal relationship of aspirin on lung cancer risk. Findings: Sixteen eligible studies involving 1,522,687 patients were included. The combined RR of aspirin use for lung cancer risk was 0.95 (95% confidence interval (CI) 0.91-0.98). In terms of pathology, a significant protective effect of aspirin on lung cancer was observed in squamous cell lung cancer (RR=0.80; 95% CI 0.65-0.98). In subgroup meta-analyses, significant association between aspirin use and reduced lung cancer risk was only observed among men (RR=0.87; 95% CI 0.77-0.97). The MR risk analysis suggested a causal effect of aspirin on lung cancer risk, with evidence of a decreased risk for overall lung cancer (OR=0.042; 95% CI 0.003-0.564) and squamous cell lung cancer (OR=0.002; 95% CI 1.21×10-5-0.301). Interpretation: Our study provided evidence for a causal protective effect of aspirin on lung cancer risk among men, particularly on the squamous cell lung cancer risk. Funding Statement: National Key RD Key Project of Guangzhou Scientific Research Project; High-level university construction project of Guangzhou Medical University Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: No patients participated in study design, patient recruitment and research conduct. Therefore, there is no need for ethical approval.

High-throughput sequencing for confirmation of suspected 2019-nCoV infection identified by fluorescence quantitative polymerase chain reaction.

To the Editor: Identifying the pathogen from clinical samples is crucial for the diagnosis of a newly emergent infectious disease, such as 2019 novel coronavirus (2019-nCoV), which has posed great threats to global public health.[1] In some cases, despite the positive epidemiological, clinical, and radiographic evidence, coronavirus disease 2019 (COVID-19) diagnosis can still be restricted by inconclusive polymerase chain reaction (PCR) results.[2] For samples of suspicious patients, where the fluorescence quantitative PCR (FQ-PCR) results in a few respiratory tract specimens were inconclusive, high-throughput sequencing (HTS) can be an effective confirmation method. Here, we report our experience of applying HTS to confirm a suspected 2019-nCoV infection. Three upper respiratory tract specimens including throat or nasal swabs were collected from a 65-year-old pneumonia patient with suspected history of contact with COVID-19 patients in Guangzhou on January 22 and 23, 2019. Patient consent was not applicable for this study as the samples were obtained as part of a routine diagnostic procedure. All the clinical specimens were handled at the State Key Laboratory of Respiratory Disease, Guangzhou, China. The initial 2019-nCoV screening results of the sample was negative by FQ-PCR with a commercial FQ-PCR kit (cycle threshold [CT] values of open reading frame 1ab [ORF1ab] and nucleoprotein [N] genes were >40 [#1 throat swab sample], where CT > 40 is considered negative). In view of the epidemiological link and clinical symptoms of the patient, a second screening using another FQ-PCR kit was performed and the range of CT value was weakly positive for the 2019-nCoV viral RNA (CT values of ORF1ab/ envelope protein [E]/N genes of three samples were 34.44/31.58/35.50 [#1 throat swab sample], >40/36.37/38.45 [#2 nasal swab sample], and 33.40/34.36/33.10 [#3 throat swab sample]). The test results of the two kits were inconsistent; therefore, to make a definite diagnosis, we performed meta-transcriptomic sequencing using the same throat swab sample (#1 throat swab sample) from the patient. A meta-transcriptomic library was constructed for single-end (75 base pairs) sequencing on the Illumina NextSeq 550Dx (Illumina, San Diego, CA, USA). The sequencing data were analyzed with the rapid pathogen detection (RPD-seq) system of the Sagene Company in Guangzhou, China, as previously reported.[3] In total, we obtained ten unique sequence reads that completely mapped onto the 2019-nCoV genome (GenBank accession No. MN908947.3). We considered this sample to be weakly positive rather than contaminated, based on the results that the ten reads are evenly distributed throughout the entire gene sequence of the virus. It is worth noting that these regions of ORF1ab, E and N genes were used as the standard PCR targets [Figure 1].Figure 1: High-throughput sequencing for 2019 novel coronavirus (2019-nCoV) of the throat swab sample (#1) from the patient. Ten unique reads were found, and eight of them on the largest ORF1ab gene, while one of them was located on the second largest spike protein gene-S and another one on the envelope protein gene-E of the 2019-nCoV genome.According to the national diagnosis and treatment plan released by the National Health Commission of the People's Republic of China, positive viral RNA FQ-PCR or virus gene sequencing results were the diagnostic criteria of COVID-19.[4] However, the different performance of FQ-PCR kits may lead to inconsistent results. Here we reported a case with inconsistent FQ-PCR results, for which the HTS was used to make a further diagnosis of the 2019-nCoV infection. Although HTS may be too costly and labor intensive for routine diagnosis, we believe that it can be used for further diagnosis of patients with COVID-19 with unclear FQ-PCR results under the condition of strict operation and quality control. Acknowledgements The authors are greatly indebted to Prof. Sooksan Wong, for her valuable suggestions on writing of the manuscript. Funding This work was supported by grants from the National Key Research and Development Program of China (Nos. 2018YFC1200100 and 2018YFC1311900), science research project of the Guangdong Province (No. 2019B030316028), and Guangzhou Medical University High-level University Clinical Research and Cultivation Program (Nos. [2017]159 and 160). Conflicts of interest None.

Performance of Initial Screening Tests for Colorectal Cancer and Subsequent Adherence to Colonoscopy: An Ecological Study

Background: Adherence to colonoscopy in colorectal cancer (CRC) screening is at a low level and varies greatly across populations. No study has examined the influencing factors of colonoscopy adherence at a population level, and this remains to be an unaddressed knowledge gap. We therefore aimed to analyze the correlation between performance of initial CRC screening tests and subsequent adherence to colonoscopy base on an ecological evaluation. Methods: The sensitivity, specificity, and positive predictive value (PPV) of initial CRC screening tests and subsequent adherence to colonoscopy in different populations were extracted from relevant studies published in English up to December 31, 2018. The age-standardized incidences (ASR) of CRC across populations in the year of screening were obtained from the Cancer Statistics data. Locally weighted regression smoothing was used to examine the relationship between adherence to colonoscopy and ASR of CRC. Cut-off points of adherence on ASR were identified by Joinpoint Regression and used in Regression Discontinuity as potential thresholds. Spearman’s correlation analysis was used to calculate correlation coefficients. Findings: We identified 192 eligible articles. The median and interquartile range of adherence to colonoscopy was 82·5% (71·8%-90·5%). The adherence was significantly correlated with ASR of CRC in the study populations (r=0·187, p<0·001) and marginally with the PPV of initial screening tests (r=0·105, p=0·077). The change points of the adherence to colonoscopy were identified at the ASR of 32·5 and 142·5/100,000, and the ratio of adherence to colonoscopy at 143/100,000 was 0·900. In countries / areas with a moderate ASR, adherence to colonoscopy was negatively correlated with the sensitivity (r=-0·367, p=0·023) and positively with the PPV (r=0·143, p=0·040), whereas in populations with a high ASR, flexible sigmoidoscopy was more widely used as an initial screening test and achieved a high subsequent adherence to colonoscopy. Interpretation: Adherence to colonoscopy is correlated with the performance of initial screening tests, particularly among populations with moderate CRC incidence. Initial screening tests with high PPV or specificity may help to increase population adherence to colonoscopy, but different strategies should be used in countries / areas with a high or moderate incidence of CRC. Funding Statement: This study was supported by the Local High Level University Construction Project of Shanghai and the Health Commission of the Pudong New Area of Shanghai (PW2019A-5). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Not required.

EMC6 and APAF1 Promote Acinar Cell Injury in Acute and Chronic Pancreatitis

Background: Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Methods: Human pancreatic tissues including AP, CP and healthy volunteers were collected during surgery. Humanized PRSS1 transgenic mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1 transgenic AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qPCR, western blotting, immunohistochemistry, immunofluorescence and immunoelectron microscopy for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Findings: Humanized PRSS1 transgenic mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. 1) increased expression of EMC6 and APAF1 was observed in patient and mouse AP/CP tissues; 2) inhibition of the two proteins resulted in attenuation of apoptosis and inflammation; 3) inhibition of EMC6 was associated with decreased expression of APAF1, suggesting a potential mechanistic connectivity. Interpretation: EMC6 and APAF1 are strongly associated with pancreatitis development, and may represent therapeutic targets for the treatment of pancreatic inflammatory diseases. Funding Statement: The article is supported by Guangdong Science and Technology Planning Project (2019A030317018) & Scientific Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (CX2018N012) & Clinical Research Program of Nanfang Hospital, Southern Medical University (2018CR046) & College Students’ Innovative Entrepreneurial Training Plan Program (201812121128, 201812121263) & Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2016PY011) & National Natural Science Foundation of China (81801487). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Written consent was obtained from each patient before the study, which were approved by the Ethics Committee of the Southern Medical University. The experimental operations were carried out in strict accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and were approved by the Institutional Animal Care and Use Committee of Southern Medical University.

Practice of China's New High-level University of Science and Engineering’s International Development: A Case Study of Dongguan University of Technology

Higher education’ internationalization connects well with the Belt and Road Initiative and Guangdong-Hong Kong-Macao Greater Bay Area construction. New type of high-level university of science and engineering’ international development is of great significance. Take Dongguan University of Technology as an example and analyze its strategy and practice. We find DGUT constructed an extensive and in-depth network of international cooperation, pushed forward multiple, characteristic and cross-border cooperation in running universities and colleges, created disciplines and subjects which have prominent advantages, attached importance to both external and internal training, enhanced internationalization ability of teachers and management teams.

COVID-19 Outbreak Improves Attractiveness of Careers in Medicine in China: A Cross-Sectional Survey in High School Students and Parents

Background: The shortage of healthcare workers is becoming a serious global problem. The underlying reasons may be specific to the healthcare system in each country. Over the past decade, medicine has become an increasingly unpopular profession in China due to the heavy workload, long-term training, and inherent risks. The ongoing COVID-19 pandemic has placed the life-saving roles of healthcare professionals under the spotlight. This public health crisis may have a profound impact on career choices in the young generation of Chinese. Methods: We conducted a questionnaire-based online survey on high school students and their parents from 24 provinces (or municipalities) of China. We investigated the change of interest in medical study due to the outbreak of COVID-19 and the motivational factors. Pearson correlation analysis was used to assess the correlation of static or dynamic interest of medical career selection with the reported number of COVID-19 cases. Maslow’s Hierarchy of Needs was used to explore underlying motivations for selection of medical-related degrees. The logistic regression model was adopted to analyze the main factors associated with students’ choices. Findings: A total of 21,085 students and 21,009 parents were included in the study. We observed an increased preference for medical study since the outbreak of COVID-19 in both students (17·5% to 29·6%) and parents (37·1% to 47·3%). Contribution to society and interest in medicine was rated as the main motivations. Additionally, students who were female, in the resit of graduate year and outside of Hubei province were significantly associated with a keen interest in medical study. Interpretation: This first multi-center cross-sectional study explores the positive change and noble motivations of students’ preferences in medical study during the COVID-19 pandemic. A longitudinal study is required to determine the persistence of their choices. Funding Statement: The Local High Level University Construction Project of Shanghai, China. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional review board of the Fudan University School of Public Health. Informed consent was waived because the questions were answered anonymously.

Radiosensitivity-Related Genes and Clinical Characteristics of Nasopharyngeal Carcinoma

Background and purpose: Radioresistance is one of the main obstacles limiting the therapeutic efficacy of chemoradiotherapy (CRT) and favorable patient prognoses, and the molecular mechanisms underlying this type of resistance remain unclear. The purpose of this study was to identify characteristic genes involved in chemoradiotherapy resistance in nasopharyngeal carcinoma (NPC). Materials and methods: Clinicopathological data of 185 patients with NPC treated at Nanfang Hospital of Southern Medical University between January 2013 and December 2014 were retrospectively analyzed. SPSS statistical software was used to analyze the clinicopathological data related to radiotherapy efficacy. Three patients who achieved complete remission and three with disease progression after CRT were selected. Differentially expressed genes (DEGs) were screened via mRNA microarray analysis of primary diagnostic endoscopy specimens. Results: The peripheral blood leukocyte count, platelet count and EBV-DNA copy number in NPC patients who were resistant to radiotherapy were higher than those in NPC patients who were sensitive to radiotherapy. The RobustRankAggreg (RRA) analysis method identified 392 DEGs, and the 66 most closely related genes among the DEGs were identified from the PPI network. Conclusion: The results of this study indicate that screening for DEGs and pathways in NPC using integrated in silico analyses can help identify a series of genetic and clinical signatures for NPC patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Funding Statement: This work was supported by the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2019ZD008); the Clinical Research Startup Program of Nanfang Hospital (2018CR021);the National Natural Science Foundation of China (Grant Nos. 81602685 and 81672992); the Science and Technology Projects in Guangdong Province (Grant Nos. 2018-1201-SF-0019 ); the Health & Medical Collaborative Innovation Project of Guangzhou City, China (201803040003); and the Natural Science Foundation of Guangdong Province (Grant No. 2017A030313486); the Natural Science Foundation of Fujian Province (Grant No. 2017J01245). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The protocol was approved by the ethics committee of Nanfang Hospital and implemented in accordance with the principles of the Declaration of Helsinki. All participants provided informed consent.

Stepwise Diagnosis and Dynamic Change&nbsp;Prediction AI System for COVID-19

Background: As the COVID-19 pandemic continues to spread worldwide, there is still no accurate rapid diagnostic test for COVID-19, or monitoring tool for patient’s clinical course. An artificial-intelligence system (CoviDet) was therefore developed and applied on chest computed tomography (CT), to evaluate its application for rapid diagnosis and potential monitoring of COVID-19 patients. Methods: 1,201,074 CT slices from 2527 patients were grouped into 3 main groups: COVID-19 positive group, non-COVID-19 viral pneumonia group and control group. They were used to train and validate CoviDet novel stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. A subset of COVID-19 patients with more than 3 consecutive CT images were selected for training and validation of the auto-segmentation and monitoring algorithm. Findings: CoviDet outperforms radiologists, and can diagnose COVID-19 based on CT alone with sensitivity of 0.93, specificity of 0.95 and AUC of 0.98 (95%CI 0.97-0.99; P<0.001). Its auto-segmentation analyses co-related well with those by radiologists, with a Dice's coefficient of 0.77. Its can generate a predictive curve of patient’s clinical course if serial CT assessments are available. Interpretation: CoviDet is a useful aid for radiologist to diagnose COVID-19 rapidly and accurately based on CT, with or without clinical data. It can produce an objective predictive curve of patient’s clinical course for easy visualisation. In principle, CoviDet could be used on a web-based platform with built auto masking of privacy data, whereby clinicians can upload anonymised CT for COVID-19 analysis without sensitive clinical information, from anywhere in the world. Funding Statement: This study is supported by High-level university construction project of Guangzhou medical university (Grant No. 20182737, 201721007, 201715907, 2017160107); the Guangdong high level hospital construction reaching peak plan. Declaration of Interests: Qiang Du is the Founder and CEO of Beijing XiaoBaiShiJi Network Technical Co. Ltd. All other authors declare no competing interests. Ethics Approval Statement: This study is approved by the ethics committee of the First Affiliated Hospital of Guangzhou Medical University.

Long Non-Coding RNAs Suppressed Cell Cycle in Lung Adenocarcinoma

BACKGROUND/AIMS: Lung cancer is the leading cause of cancer-associated mortality worldwide. Long noncoding RNAs (lncRNAs) have been found to be related to different cancers and play important roles in regulating the pathological and physiological processes of numerous cancers. The aim of the current study was to identify potential prognostic long non-coding RNA biomarkers for predicting survival in patients with lung adenocarcinoma (LUAD) using The Cancer Genome Atlas (TCGA) dataset. METHODS: The clinical pathology and gene expression profiles of lung cancer were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs were identified and patient survival analysis performed. The prognostic signature was further evaluated by functional assessment and bioinformatics analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to predict the function of lncRNAs and to construct a gene co-expression network relationship to predict downstream target genes with the aid of the STRING database and Cytoscape software RESULTS: lncRNA RP11-434D9.1 and FENDRR had lower expression levels in lung cancer and were associated with poor prognoses. We found that the major functions of lncRNA RP1-434D9.1 and FENDRR were related to the cell cycle, and we further screened out the possible downstream target genes CDK1, CCNB1, CCNB2, CCNA1, AURKA, PLK1. CONCLUSIONS: LncRNA RP11-434D9.1 and FENDRR can be used as molecular biomarkers for the diagnosis and prognosis of lung adenocarcinoma. These dysregulated lncRNAs might negatively regulate cell cycle through the hub genes, which then affected cancer cell proliferation. These results may provide new ideas for further clinical research for markers used for lung cancer diagnosis and prognosis. FUNDING STATEMENT: This work was supported by National Natural Science Foundation of China (81672270); Key project of Guangzhou Science Technology and Innovation Committee (201707020042); Science and Technology Program of Guangzhou (201803010024); Science and Technology Planning Project of Guangdong Province, China (2017B020226005); Science and Technology Program of Guangzhou (201903010003). Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2016PY013); Scientific Research Projects of Wu Jieping Medical Research Foundation (320.6750.17206). DECLARATION OF INTERESTS: The authors declare that no conflicts of interest exist. ETHICS APPROVAL STATEMENT: Every specimen was anonymously handled based on ethical standards. All participants provided signed informed consent and our study had full approval from the hospital’s Ethical Review Committee.

Research on the Relationship between the Preponderant and Characteristic Disciplines of a High-level University and the National Innovation-Driven Development Strategy

Taking Harbin Institute of Technology (HIT) as an example, this paper selects 5 preponderant and characteristic disciplines, using the Delphi method to make a thorough study by investigating 89 experts of 5 disciplines from HIT to deeply explore and research the problem of The fitness degree of the preponderant and characteristic disciplines and the national innovation-driven development By the study of three round iterations of Delphi method, the experts have made an authoritative consensus based on the present situation of the disciplinary innovation ability of HIT. It evaluates the innovation ability of the preponderant and characteristic disciplines and the degree of fitness between these advantages and the national strategy. It is believed that the promotion of the innovation ability of the disciplines is beneficial to the fitness. It also points out the main factors that restrict the improvement of disciplinary innovation ability.

Influence of intraband motion on the interband excitation and high harmonic generation**Project supported by the National Natural Science Foundation of China (Grant Nos. 11674209 and 11774215), the High Level University Projects of Guangdong Province of China (Mathematics, Shantou University), and the Open Fund of the State Key Laboratory of High Field Laser Physics (SIOM), China. WFY and XHS acknowledge support

Tunnelling, acceleration, and collision of electrons are the basic events in the process of high harmonic generation (HHG) in strong-field interaction with atoms. However, the periodic array of atoms in semiconductor structure makes three steps become interatomic coherent process which leads to complicated carrier dynamics and two sources of high harmonic emission: interband polarization and intraband current. The difference of features of high harmonic generation between semiconductors and atoms is strongly linked to the unique presence of intraband motion which manifests itself a nontrivial role in intertwined two dynamics. Here, we review recent experimental and theoretical advances of understanding coupled interband and intraband mechanisms of HHG in semiconductors. Particularly we focus on the influence of intraband motion on the interband excitation, and on the subsequent HHG emission and attosecond pulse generation.

Liraglutide Alleviates Hepatic Steatosis and Liver Injury in T2MD Rats via a GLP-1R Dependent AMPK Pathway

Nonalcoholic fatty liver diseases (NAFLD) ranging from nonalcoholic fatty liver to non-alcoholic steatohepatitis have a high preference in Type 2 diabetes mellitus (T2DM) patients. However, no antidiabetic drug is approved for the treatment of NAFLD in T2DM patients. Although multiple daily injection of basal-bolus insulin is the final therapeutic process for T2DM, we found that insulin treatment aggravated hepatic steatosis and oxidative stress in ZDF rats. Here, besides glycemic control, we demonstrated a stimulatory role of liraglutide in relieving hepatic steatosis and liver injury in ZDF rats. Interestingly, liraglutide could also alleviate the insulin aggravated hepatic fatty accumulation. GLP-1 agonist (liraglutide and Ex-4) activated the expression of peroxisome proliferator-activated receptor α (PPARα) via a GLP-1R dependent AMPK pathway. As a nuclear transcription factor, PPARα could mediate the effect of GLP-1 in alleviating hepatic steatosis through differentially regulating the expression of its targeting genes including acetyl CoA carboxylase (ACC) and carnitine palmitoyl transferase la (CPT1a) both in vitro and in vivo. Moreover, our results indicated that GLP-1 could relieve liver injury through decreasing the oxidative stress that stimulated by hepatic steatosis. Insulin might aggravate hepatic steatosis and liver injury through inhibiting the expression of GLP-1R. In this research, we investigated the feasibility of liraglutide treatment combined with basal insulin in attenuating hepatic steatosis and liver injury in ZDF rats, as well as the mechanism behind, which will provide a theoretical basis for the combination treatment recommended by the latest clinical practice guidelines for T2DM. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81270966, 81500679, 81702903, 81770821), the Natural Science Foundation of Guangdong Province, China (Grant Nos. 2014A030310036, 2014A030310472, 2017A030310038, 2017A030313519 and 2018A030313609), Science and Technology Plan of Guangdong Province (Grant No. 2016A020215097, 2017A020215045) and the Guangdong Provincial Department of Education High-level University Construction Funding Southern Medical University Clinical Research Startup Program (LC2016YM007). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All animal experiments were approved by the Institutional Animal Care and Use Committee of Southern Medical University (Guangzhou, China).

Physical classroom environment affects students’ satisfaction: Attitude and quality as mediators

Boosting student satisfaction with courses is undoubtedly a key challenge for higher education institutions. Our research was designed to understand better the role of the physical classroom environment, attitude toward the course, and perception of the quality of the course in forming student satisfaction with the course. Responses to paper-based surveys were collected during classes from students majoring in hospitality and tourism in 5 high-level universities in South Korea. We analyzed 401 responses by using a series of multiple regression analyses based on forward selection. The results showed that air quality, odor, noise, and equipment/amenity are essential physical classroom environment factors in determining attitude, perception of quality, and satisfaction. Attitude toward the course completely mediates the effect of odor on satisfaction, and quality partially mediates the impact of equipment/amenity on satisfaction. Overall, in this study we identified the salient role of certain features of the classroom physical environment in building students’ satisfaction with a course via attitudes toward, and evaluation of the quality of the course.

Research on the Construction Path of High-level Universities under the Background of “Double World-Class” in China: Taking Jiangsu Province as an Example

Under the background of China’s “Double World-Class” construction, the paper takes high-level universities in Jiangsu Province as the research sample, and adopts a case study method to study the connotation of high-level universities, the effectiveness and problems of high-level university construction in Jiangsu Province. Based on this, the path selection of high-level university construction in Jiangsu Province is proposed, which is to optimize the education structure, clarify the school goals, strengthen the discipline construction, improve the education evaluation mechanism, enhance the level of education internationalization, enhance the ability of serving economic and social development, and promote Jiangsu Province marching from the “Great Province of Higher Education” toward “Strong Province of Higher Education”.

Research on the Construction Path of High-Level Universities Under the Background of 'Double World-Class' in China: Taking Jiangsu Province as an Example

Under the background of China’s “Double World-Class” construction, the paper takes high-level universities in Jiangsu Province as the research sample, and adopts a case study method to study the connotation of high-level universities, the effectiveness and problems of high-level university construction in Jiangsu Province. Based on this, the path selection of high-level university construction in Jiangsu Province is proposed, which is to optimize the education structure, clarify the school goals, strengthen the discipline construction, improve the education evaluation mechanism, enhance the level of education internationalization, enhance the ability of serving economic and social development, and promote Jiangsu Province marching from the “Great Province of Higher Education” toward “Strong Province of Higher Education”.

P53 Activated by ER Stress Suppresses Caerulein-Induced Acute Pancreatitis Progression in Humanized PRSS1 Transgenic Mice by Inducing Acinar Cell Apoptosis

Background: Acute pancreatitis is a severe pancreatic disorder that remains associated with high mortality due to a lack of effective drugs and management strategies. This study aimed to investigate the molecular pathogenic mechanisms of acute pancreatitis involving p53 and endoplasmic reticulum (ER) stress pathways. Methods: Expression of PRSS1 and p53 in human acute pancreatitis tissues was detected by immunohistochemistry and western blotting. Acute pancreatitis was induced with caerulein in humanized PRSS1 transgenic mice, and its severity was verified by histological imaging, evaluation of edema, and serum amylase and trypsin activity assays. A transferase mediated d-UTP nick end-labeling assay was performed to evaluate acinar cell apoptosis associated with acute pancreatitis. The expression of ER stress genes was assessed by quantitative RT-PCR (qRT-PCR) and western blotting. Results: PRSS1 and p53 were highly expressed in human acute pancreatitis tissues. Expression of human PRSS1 in caerulein-treated mice induced significant acinar cell apoptosis and acute pancreatitis progression. p53 knockout significantly aggravated acute pancreatitis progression in humanized PRSS1 transgenic mice. The ER stress pathway was activated by PRSS1 and mediated the progression of acute pancreatitis in mouse pancreatic tissues. Application of a p53 inhibitor promoted caerulein-induced acute pancreatitis in PRSS1 transgenic mice, while a p53 activator ameliorated the progression of acute pancreatitis. Conclusion: P53, which was activated by the ER stress pathway, suppresses the progression of acute pancreatitis in mice expressing PRSS1 by inducing acinar cell apoptosis. Funding: The article is supported by Scientific Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (CX2018N012) & Clinical Research Program of Nanfang Hospital, Southern Medical University (2018CR046) & Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2016PY011). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: All experimental procedures performed with mice were approved by the Institutional Animal Care and Use Committee of Southern Medical University.

Assessment Awareness of Public About Breast Cancer and its Screening Measurements in Asir Region, KSA.

Breast cancer (BC) has a major impact on women's health worldwide. The Kingdom of Saudi Arabia is no exception, where it is considered the most common malignancy, embodying the second leading cause of cancer deaths after lung cancer. In today's world, people are more health conscious and more aware of different medical specialties. Despite the tremendous advancements in education, there seems to be a limited knowledge among the public regarding this issue. Various studies have been conducted in many regions to determine the perception/awareness about breast cancer. The present study is of the first of its type in our region, assessing the awareness of the public about breast cancer and its screening measurements. As per our knowledge, there is no study that estimated the awareness of breast cancer and its screening measurements among the public in the Asir region. Therefore, this study aims to estimate the awareness of breast cancer and its screening measurements among public and assess the knowledge about Breast Self-Examination (BSE) and their opinion about its effectiveness in early diagnosis of breast cancer to detect the relationship between awareness and socioeconomic status. This study is a cross-sectional prospective study, with a sample of 1046 participants aged between 12 and 80years (male and female) from the Asir region evaluated by questionnaire after attaining consent. The selection of participants was based on the simple random sampling method. The majority of participants were of age 20 to less than 30years (56.9%). About half of them were males (52.7%). The majority was single (61.2%). Most of them (74.0%) have a high education level (University and more). About one-third of the participants (32.7%) worked in the medical field, and most of them worked in the non-medical field (46.6%). Regarding general knowledge, the score was 60.2%, which represented a relatively good knowledge. The overall knowledge regarding breast cancer as recorded by our population reported that only 18.8% had good knowledge. Participants of this resettlement colony have poor knowledge about breast cancer, be it about risk factors, signs, and symptoms, or early detection procedures, where the overall knowledge score was only 18.8%.

Concomitant Mutation Patterns of EGFR 19Del and L858R and Their Association with Primary Response to EGFR-TKIs in NSCLC Patients

Background: Epidermal growth factor receptor (EGFR) 19 exon deletion (19del) has been observed to be associated with better outcomes in treatments with EGFR-TKIs than L858R mutation (L858R). It is of interest to explore whether the respective concomitant mutational profiles of 19del and L858R may explain their different sensitivities to EGFR-TKIs. Methods: We obtained next generation sequencing data to comprehensively determine the mutational profile of EGFR mutated patients from two cohort: our center (G1 cohort) and database cohort (G2 cohort). Mutation status of each gene and EGFR-TKI response information was retrieved. Gene Ontology (GO) biological process enrichment analyses of mutational profile were conducted. Findings: A total of 403 adenocarcinoma patients were recruited in G1 and 915 were included in G2 cohort. Similar prevalence of total concomitant mutations was observed in both G1 (19Del 34.30% vs. L858R 35.50%; p=0.803) and G2(19Del 73.4% vs. L858R 72.4%; p=0.735) cohort. The majority of mutations distribution between the two sub-types is similar in G1 and G2, however, CTNNB1(P=0.016), NTRK1(P=0.075) and U2AF1(P=0.075) were more frequent in L858R. Through logistic regression, we found total concomitant mutations (P=0.03), EGFR mutations (P=0.04) and T790M (P=0.02) independently affected the TKI response. In addition, 19Del showed higher ORR compared with L858R, regardless of concomitant mutations. Moreover, concomitant mutations in 19Del and L858R had various enrich signal pathway. Interpretations: Our study demonstrated that the prevalence of most concomitant mutations are similar between 19Del and L858R patients. Patients with L858R showed significantly lower response than those with 19del regardless of the co-mutation status. Funding Statement: The grant 2016YFC0905400 from the National Key RD China National Science Foundation (Grant No. 81871893 & No. 81501996); Key Project of Guangzhou Scientific Research Project (Grant No. 201804020030); High-level university construction project of Guangzhou medical university (Grant No. 20182737, 201721007, 201715907, 2017160107); National key R & D Program (Grant No. 2017YFC0907903 & 2017YFC0112704). Declaration of Interests: The authors state: None declared. Ethics Approval Statement: The study protocol has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou Medical university (S-201525). Written informed consent was obtained from all patients to permit genetic analysis of biological samples.

Berberine Hydrochloride for the Prevention of Colorectal Adenomas: A Double-Blind, Randomised Controlled Multicenter Clinical Trial

Background: Chemoprevention of colorectal adenoma and cancer remains its importance in public health. The rate of adenoma recurrence in the first year after polypectomy is very high in East Asian populations. We aimed to investigate the clinical potential and safety of Berberine hydrochloride for colorectal adenoma recurrence. Methods: This double-blind, randomised, placebo-controlled clinical trial was done in seven hospital centers across six provinces in China. Patients with recently diagnosed adenomas and after complete polypectomy were recruited and randomized into a BBR group (Berberine hydrochloride 0.3g, twice daily) or a placebo group. They were anticipated for at least one follow-up colonoscopy until a diagnosis of CRA/CRC or the last enrolled patient reached the 2-year follow-up. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. The secondary outcomes were the recurrences of polypoid lesions as well as advanced adenomas or CRC. Findings: Between Nov 14, 2014 and Dec 29, 2018, 1136 patients were screened for eligibility, and 1108 underwent randomization. 553 patients were assigned to receive Berberine hydrochloride and 555 to placebo. An unadjusted RR for recurrent adenomas and all polypoid lesions were 0.77 (95% CI, 0.66 to 0.91) and 0.77 (95% CI, 0.67 to 0.89), representing a decrease of 22.72% and 22.70%, respectively. No CRC occurred during the whole trial. Interaction test showed taking BBR was effective in female with unadjusted RR for recurrent adenomas of 0.58 (95% CI, 0.41 to 0.81); P=0.07 (Alpha = 0.10). No serious adverse events were reported. Interpretation: Although the mechanism has not been fully elucidated yet, Berberine hydrochloride was effective to reduce colorectal adenoma recurrence after polypectomy. Trial Registration: This trial is registered with ClinicalTrials.gov number NCT02226185. Funding Statement: This project was supported by grants from the National Natural Science Foundation of China (81421001, 81530072, 81830081 and 8177100232), the funds from Shanghai Shenkang Center (SHDC12018121), from Shanghai Municipal Key Clinical Specialty, and from Innovative research team of high-level local universities in Shanghai. The project was also partially supported by Top-Notch project of China and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20152514). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Approval for this study was obtained from the Ethics Committee of Renji Hospital, Shanghai Jiao-Tong University School of Medicine on 13th August 2014. The protocol and informed consent forms were also approved by the institutional ethics committees at each of the participating clinical centers.

Serum Amyloid A1 As a Biomarker for Radiation Dose Estimation and Lethality Prediction in Irradiated Mouse

Background: Fast and reliable biomarkers are needed to distinguish whether individuals were exposed or not to radiation and assess radiation dose, and to predict the severity of radiation damage in a large scale radiation accident. Serum Amyloid A1 (SAA1) is a protein induced by multiple factors including inflammatory. Therefore, this study aimed at exploring the role of SAA1 in the radiation dose estimation and lethality prediction after radiation. Methods: C57BL/6J female mice were exposed to total body irradiation (TBI) at different doses and time points and amifostine, a drug used to reduce the side effects of radiotherapy, was injected before irradiation. Patients with nasopharyngeal carcinoma subjected to radiotherapy were used as the irradiation model in humans. Findings: A moderate SAA1 increase was observed at 6 hours in serum samples from irradiated mice at all doses used, with a peak at 12 hours, then decreased to day 3 after exposure. A second SAA1 increase was observed from day 5 to 7, which was associated to subsequent lethality. Treatment with amifostine before irradiation could prevent mice death and inhibit the second SAA1 increase. SAA1 increase after radiation was confirmed in human serum of nasopharyngeal carcinoma patients after radiotherapy. Interpretation: Serum SAA1 levels could represent a biomarker for radiation dose estimation and its second increase might be a useful lethality indicator after radiation in a mouse model. Clinical Trial Registration: All specimens derived from a Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2016 PY015). Funding Statement: This work was supported by the Major Project: BWS18J008. Declaration of Interests: The author declares no conflicts of interest. Ethical Approval Statement: the research protocol was approved by the ethics committee/institution (No.NFEC-2018-013).