Nondestructive technique for identifying nuclides using neutron resonance transmission analysis at CSNS Back-n

Nondestructive and noninvasive neutron assays are essential applications of neutron techniques.Neutron resonance transmission analysis(NRTA)is a powerful nondestructive method for investigating the elemental composition of an object.The back-streaming neutron line(Back-n)is a newly built time-of-flight facility at the China Spallation Neutron Source(CSNS)that provides neutrons in the eV to 300 MeV range.A feasibility study of the NRTA method for nuclide identification was conducted at the CSNS Back-n via two test experiments.The results demonstrate that it is feasible to identify different elements and isotopes in samples using the NRTA method at Back-n.This study reveals its potential future applications.

Cumulative scores based on plasma D-dimer and serum albumin levels predict survival in esophageal squamous cell carcinoma patients treated with transthoracic esophagectomy

Background:Recently,studies have shown that plasma D-dimer and serum albumin are prognostic markers for esophageal cancer.The purpose of this study was to evaluate a novel prognostic scoring system—DA score(combination of preoperative plasma D-dimer and serum albumin levels)—and analyze the association between survival of patients with esophageal squamous cell carcinoma(ESCC) and their Glasgow prognostic score.Methods:In this retrospective study,preoperative biochemical markers and clinicopathologic factors in 260 ESCC patients treated with transthoracic esophagectomy were reviewed.According to receiver operating characteristic analysis,the cutoff values of D-dimer and albumin were defined as 0.5 μg/mL and 43.8 g/L,respectively.Patients with high D-dimer levels(>0.5 μg/mL) and low albumin levels(<43.8 g/L) were assigned a score of 2,those with only one of the two abnormalities were assigned a score of 1,and those with neither of the two abnormalities were assigned a score of 0.Results:ESCC patients with a DA score of 0,l,and 2 numbered 55,116,and 89,respectively.Survival analysis showed that patients with a DA score of 2 had lower overall survival(OS) rates than those with DA scores of 1 and 0(37.1%vs.52.6%and 76.4%,P < 0.001);similar findings were observed for disease-free survival(DFS) rates(32.6%vs.44.8%and67.3%,P < 0.001).In addition,the predictive value of the DA score was also significant in patients with stages l-IIA and stages IIB-IV ESCC.Multivariate Cox regression analyses indicated that hazard ratios(HRs) for predicting OS of patients with DA scores 1 and 2 were 2.25 {P — 0.010) and 3.14(P< 0.001),respectively,compared with those with a DA score of 0,and HRs for predicting DFS of patients with DA scores of 1 and 2 were 1.86(P = 0.023) and 2.68(P < 0.001),respectively,compared with those with a DA scores of 0.Conclusions:Our study suggests that preoperative DA scores are notably associated with postoperative survival of ESCC patients.

Plasma microRNA profiling in nasopharyngeal carcinoma patients reveals miR-548q and miR-483-5p as potential biomarkers

MicroRNAs(miRNAs), which play a role in tumorigenesis, may also serve as diagnostic or prognostic biomarkers. However, studies on human miRNA profiles in plasma from nasopharyngeal carcinoma(NPC) patients are in their infancy. Here, we used microarrays to perform systematic profiling of human miRNAs in plasma from NPC patients. We subsequently used real-time quantitative polymerase chain reaction(Q-PCR) to validate miRNAs with aberrant expression that could serve as potential biomarkers. By comparing the plasma miRNA profiles of 31 NPC patients and 19 controls, 39 of 887 human miRNAs were found to be aberrantly expressed. Considering the fold change and P value, miR-548q and miR-483-5p were validated in 132 samples from 82 NPC patients and 50 controls. Moreover, high expression of miR-548q and miR-483-5p was further found in 3 NPC cell lines and clinical biopsy tissues from 54 NPC patients and 22 controls. Our results revealed that miR-548q and miR-483-5p are potential biomarkers of NPC. Combining the receiver operating characteristic(ROC) analyses of these 2 miRNAs, an area under the ROC curve(AUC) of 0.737 with 67.1% sensitivity and 68.0% specificity were obtained, showing the preliminary diagnostic value of plasma miRNAs. Moreover, most NPC patients with a poor outcome exhibited high expression(> median) of miR-548q(70.6%) and miR-483-5p(64.7%) in tissue samples, indicating their prognostic value. The high expression levels of miR-548q and miR-483-5p in plasma, cell lines, and clinical tissues of NPC patients indicate that their roles in NPC should be explored in the future.

A comprehensive genomic characterization of esophageal squamous cell carcinoma: from prognostic analysis to in vivo assay

Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer death worldwide and is char?acterized by numerous genetic mutations. TNM staging is not sufficient for predicting patient outcomes. Addition?ally, ESCC shows poor responsiveness to chemotherapy and radiation. Thus, there is an urgent need to find efficient therapy targets. Previous ESCC high?throughput genomic studies have lacked intensive survival analysis, particularly for copy number variation(CNV) and the genes involved.Main body: In the study "Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis" recently published in the American Journal of Human Genetics, we comprehensively analyzed the effects of CNVs, mutations, and relative gene expression on patient outcomes. To validate our findings for our 67 sequencing samples, we collected a 321?patient retrospective cohort with detailed 5?year follow?up information and carried out univariate and multivariate survival analyses. In addition, the biological functions of the survival predictors in ESCC were investigated both in vitro and in vivo.Conclusions: We found the independent ESCC survival predictors and potential therapy targets. Nevertheless, the effects of numerous low?frequency mutations need to be explored using larger sample sequencing. Overall, con?structing multi?gene prognostic signatures will remain a great challenge in the future.

Association of the Asp312Asn and Lys751 Gln polymorphisms in the XPD gene with the risk of non-Hodgkin's lymphoma:evidence from a meta-analysis

Polymorphisms in DNA repair genes may alter DNA repair capacity and,consequently,lead to genetic instability and carcinogenesis.Several studies have investigated the association of the Asp312 Asn and Lys751 Gln polymorphisms in the xeroderma pigmentosum complementation group D {XPD) gene with the risk of non-Hodgkin's lymphoma(NHL),but the conclusions have been inconsistent.Therefore,we performed this meta-analysis to more precisely estimate these relationships.A systematic literature search was performed using the PubMed,Embase,and Chinese Biomedical(CBM) databases.Ultimately,6 studies of Asp312 Asn,comprising 3,095 cases and 3,306 controls,and 7studies of Lys751 Gln,consisting of 3,249 cases and 3,676 controls,were included.Pooled odds ratios(ORs) and 95%confidence intervals(CIs) were calculated to assess the strength of each association.Overall,no association was observed between the Asp312 Asn polymorphism and NHL risk(homozygous:OR = 1.11,95%CI = 0.94-1.32;heterozygous:OR = 1.00,95%CI = 0.89-1.11;recessive:OR = 1.12,95%CI = 0.95-1.31;dominant:OR = 1.02,95%CI = 0.92-1.13;and allele comparison:OR = 1.04,95%CI = 0.96-1.12) or between the Lys751 Gln polymorphism and NHL risk(homozygous:OR = 0.97,95%CI = 0.83-1.15;heterozygous:OR = 0.96,95%CI = 0.86-1.06;recessive:OR = 1.00,95%CI = 0.86-1.16;dominant:OR = 0.96,95%CI = 0.87-1.06;and allele comparison:OR = 0.98,95%CI = 0.91-1.05).Furthermore,subgroup analyses did not reveal any association between these polymorphisms and ethnicity,the source of the controls,or the NHL subtype.These results indicated that neither the Asp312 Asn nor Lys751 Gln XPD polymorphism was related to NHL risk.Large and well-designed prospective studies are required to confirm this finding.

Centrifugation: an important pre-analytic procedure that influences plasma microRNA quantification during blood processing

Circulating microRNAs are robustly present in plasma or serum and have become a research focus as biomarkers for tumor diagnosis and prognosis.Centrifugation is a necessary procedure for obtaining highquality blood supernatant.Herein,we investigated one-step and two-step centrifugations,two centrifugal methods routinely used in microRNA study,to explore their effects on plasma microRNA quantification.The microRNAs obtained from one-step and two-step centrifugations were quantified by microarray and TaqMan-based real-time quantitative polymerase chain reaction(Q-PCR).Dynamic light scattering was performed to explore the difference underlying the two centrifugal methods.The results from the microarray containing 1,347 microRNAs showed that the signal detection rate was greatly decreased in the plasma sample prepared by two-step centrifugation.More importantly,the microRNAs missing in this plasma sample could be recovered and detected in the precipitate generated from the second centrifugation.Consistent with the results from microarray,a marked decrease of three representative microRNAs in twostep centrifugal plasma was validated by Q-PCR.According to the size distribution of all nanoparticles in plasma,there were fewer nanoparticles with size>1,000 nm in two-step centrifugal plasma.Our experiments directly demonstrated that different centrifugation methods produced distinct quantities of plasma microRNAs.Thus,exosomes or protein complexes containing microRNAs may be involved in large nanoparticle formation and may be precipitated after two-step centrifugation.Our results remind us that sample processing methods should be first considered in conducting research.

GWAS signals across the HLA regions:revealing a clue for common etiology underlying infectious tumors and other immunity diseases

Increasing evidence suggests that multiple genes in the human leukocyte antigen(HLA) regions play an important role in development of cancers and immunity disorders.However,the biological mechanisms of the HLA associations are not well understood.We recently conducted a survey of all genome-wide association studies(GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases.This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.

Potential factors associated with clinical stage of nasopharyngeal carcinoma at diagnosis: a case–control study

Background: In China, most patients with nasopharyngeal carcinoma(NPC) are diagnosed at a late stage and con?sequently have a poor prognosis. This study aimed to investigate potential factors associated with the clinical stage of NPC at diagnosis.Methods: Data were obtained from 118 patients with early?stage NPC and 274 with late?stage NPC who were treated at Sun Yat?sen University Cancer Center between August 2014 and July 2015. Patients were individually matched by age, sex, and residence, and a conditional logistic regression model was applied to assess the associa?tions of clinical stage at diagnosis with socioeconomic status indicators, knowledge of NPC, physical examinations, patient interval, and risk factors for NPC.Results: Although knowledge of early NPC symptoms, smoking cessation, and patient interval were important fac?tors, the number of cigarettes smoked per day, motorbike ownership, and physical examination exhibited the strong?est associations with the clinical stage of NPC at diagnosis. Compared with smoking fewer than ten cigarettes a day, smoking 10–30 cigarettes [odds ratio(OR) 4.03; 95% confidence interval(CI) 1.11–14.68] or more than 30 cigarettes(OR 11.46; 95% CI 1.26–103.91) was associated with an increased risk of late diagnosis. Compared with not owning a motorbike, owning a motorbike(OR 0.38; 95% CI 0.23–0.64) was associated with early diagnosis. Subjects who under?went physical examinations were less likely to receive a late diagnosis than those who did not undergo examinations(OR 0.50; 95% CI 0.28–0.89). However, indicators of wealth were not significant factors.Conclusions: Initiatives to improve NPC patient prognosis should aim to promote knowledge about early symptoms and detection, health awareness, and accessibility to health facilities among all patients, regardless of socioeconomic status.

诊断时鼻咽癌临床分期相关的潜在因素:一项病例对照研究

背景与目的在我国,大多数鼻咽癌(nasopharyngeal carcinoma,NPC)患者都是在晚期才被诊断出来的,并且患者预后较差。本研究旨在探讨与诊断时NPC临床分期相关的潜在因素。方法将2014年8月至2015年7月在中山大学肿瘤防治中心接受治疗的118例早期NPC患者和274例晚期NPC患者的临床数据纳入本研究。按照年龄、性别和居住地对患者进行匹配,应用条件logistic回归模型评估诊断时临床分期与社会经济状况指标、NPC的认知、体格检查、患病检查间隔时间和NPC风险因素的相关性。结果虽然早期NPC症状的认知、戒烟和患病检查间隔时间是重要因素,但患者每天的吸烟量、摩托车拥有情况和体检与诊断时NPC的临床分期密切相关。与每天吸烟少于10支相比,每天吸烟10–30支[比值比(odds ratio,OR)=4.03;95%置信区间(confidence interval,CI):1.11–14.68]或每天吸烟30支以上(OR=11.46;95%CI:1.26–103.91)延迟诊断的风险增加。拥有摩托车(OR=0.38;95%CI:0.23–0.64)比不拥有摩托车会被更早诊断出来。接受体检的患者比未接受检查的患者被延迟诊断的可能性更小(OR=0.50;95%CI:0.28–0.89)。但是,财富指标并不是显著因素。结论改善NPC患者预后的措施应旨在提高所有患者对早期症状和体检的认知、健康意识和卫生设施的可及性,而不论其社会经济状况如何。

鼻咽刷采样法:一种简便可行的鼻咽癌核酸研究的取样方法

背景与目的由于取样困难,用于鼻咽癌(nasopharyngeal carcinoma,NPC)研究的组织标本十分稀缺。既往研究表明,无创鼻咽刷采样法是一种有效的NPC诊断的取样方法。本研究旨在评估鼻咽刷采样法获取鼻咽部核酸进行研究的可行性。方法通过鼻咽刷采集24例健康人和48例NPC患者的鼻咽刷样本。通过内镜活检采集48例NPC和18例鼻咽炎患者的组织。通过定量聚合酶链反应检测两种标本中肿瘤抑制基因(tumor suppressor genes,TSGs)和Epstein-Barr病毒(Epstein-Barr virus,EBV)编码的microRNAs的表达水平及EBV DNA的拷贝数。结果在所检测的6个TSGs中,有2个基因在NPC患者鼻咽刷样本和组织样本中的表达水平显著低于健康/鼻咽炎患者。4个EBV编码的microRNA(包括mir-bart1-5p、mir-bart5、mir-bart6-5p和mir-bart17-5p)在NPC患者鼻咽刷样本和组织样本中的表达水平显著高于健康/鼻咽炎患者(P<0.001)。与健康对照组相比,EBV DNA在NPC患者的鼻咽刷样本(P<0.001)和组织样本(P<0.001)中均显著增加。结论鼻咽刷采样法可以获得足量的肿瘤样品用以病毒核酸分析,包括EBV编码的microRNAs和EBV DNA。对于TSG表达的检测,鼻咽刷采样法尽管可行,但效果不如组织活检法。本研究证实了鼻咽刷采样法是一种适用于NPC核酸研究的取样方法。

Research development of Carpesii Fructus

Carpesii Fructus is the fruit of Carpesium abrotanoides L.and is recorded in the Chinese Pharmacopoeia(2015 Edition).Carpesium abrotanoides broadly distribute in China.Traditionally,Carpesii Fructus was used as a parasiticide,especially for ascariasis,pinworms and tapeworm disease.In ancient times,the Carpesium plants were used as traditional Chinese,Korean and Japanese herbal medicines for the treatment of several diseases.Carpesii Fructus was first recorded in the book "Newly Revised Canon of Materia Medica" in the Tang Dynasty of China.The original plant is Compositae Arte.misia santonica(Seriphidium cinum) from middle east Persian.At present,Carpesium abrotanoides issometimes confused with the Lappula family in species classification.In the Song Dynasty of China,"KaiYang Materia Medica" recorded that the best Carpesii Fructus was from Persian.The main compo.nents of Carpesii Fructusare terpenes,phenolic compounds,flavonoids and coumarins.Including telekin,3-epi-isotelekin,11β-13-dihydro-1-epi-inuviscolide,carabrone,carabrol,terpene lactone,gerilin,carpesia,valeric acid,oleic acid,linolenic acid,thirty-one alkane,sterol,etc.The chemical components isolated from whole plants of carpesia are more than 143.In clinical practice,Carpesii Fructus is mainly used as antiparasitic drugs and usually combined with other drugs since the poor efficacy as single drug.Its toxic reaction is closely related to the dose of the drug.Carpesia,asa main component of Carpesii Fructus,might lead to adverse reactions also.At present,Major issuesof Carpesii Fructusare the lack of phar.macological research,as well as lack of in-depth study on the material basis.Therefore,further studies are needed on the drug development and clinical usuage.

Advances of biomarkers in nasopharyngeal carcinoma’s early detection

Nasopharyngeal carcinoma(NPC),a highly invasive and metastatic cancer,is widely prevalent in South China,Southeast Asia,and North Africa.NPC patients with stages I and II are often asymptomatic.Therefore,NPC patients are usually diagnosed with advanced-stage(stages III and IV)at their first visit.Detection of NPC at early stage is the key to improve the survival of patients.Epstein-Barr virus(EBV)plays an essential role in NPC occurrence in endemic areas.EBV-based biomarkers,including EBV antibody in serum and EBV DNA in plasma,have been specifically proposed for NPC early detection.Herein,we summarize recent advances in biomarkers for the early detection of NPC.

Alcohol and tea consumption in relation to the risk ofnasopharyngeal carcinoma in Guangdong, China

To investigate whether alcohol and tea con-sumption has an etiological association with nasophar-yngeal carcinoma(NPC)in a high-incident population,a large scale case-control study was conducted.The study included 2846 individuals in Guangdong Province,China,with 1387 newly diagnosed cases of NPC and 1459 frequency-matched controls.Exposure histories of alcohol and tea consumption were obtained via personal inter-views.Information regarding socio-demographic charac-teristics(age,sex,education,dialect and household type),family history of NPC,Epstein-Barr virus(EBV)infection,dietary habits and other potential confounding factors was also studied.An analysis was performed using uncondi-tional logistic regression to calculate odds ratios(OR)and 95%confidence intervals(CI).The risk of NPC was found to be associated with habitual alcohol consumption and tea consumption.Tea consumption has been associated with a decreased occurrence of NPC(OR=0.62),while con-sumption of alcohol was associated with a complex effect.Specifically,moderate consumption of alcohol was associated with decreased risk of NPC,while overuse,especially strong distillate spirits,appeared to be a risk factor.

Nasopharyngeal brushing: a convenient and feasible sampling method for nucleic acid-based nasopharyngeal carcinoma research

Background:Tissue specimens for nasopharyngeal carcinoma(NPC)research are scarce because of sampling dif-ficulties.Previous studies have suggested non-invasive nasopharyngeal brushing as an effective sampling method for NPC diagnosis.The present study aimed to evaluate the feasibility of nasopharyngeal brushing in the acquisition of NPC nucleic acids for research.Methods:Nasopharyngeal brushing samples were acquired from 24 healthy individuals and 48 NPC patients.Tissues from 48 NPC and 18 nasopharyngitis patients were collected by endoscopic biopsy.The expression levels of tumor suppressor genes(TSGs)and Epstein-Barr virus(EBV)-encoded microRNAs as well as EBV DNA copy number were measured by quantitative polymerase chain reaction in both types of samples.Results:Among six TSGs examined,the expression levels of two genes were significantly decreased in nasopharyn-geal brushing and tissue samples from NPC patients as compared with those from healthy/nasopharyngitis indi-viduals.Four EBV-encoded microRNAs,mir-bart1-5p,mir-bart5,mir-bart6-5p,and mir-bart17-5p,were significantly up-regulated in both NPC brushing and tissue samples compared with those from healthy/nasopharyngitis controls(P<0.001).EBV DNA was significantly increased in both nasopharyngeal brushing samples(P<0.001)and tissue sam-ples(P<0.001)from NPC patients in comparison with those from healthy controls.Conclusions:Nasopharyngeal brushing can obtain sufficient tumoral materials for the analysis of viral nucleic acid,including EBV-encoded microRNAs and EBV DNA.For the detection of TSG expression,nasopharyngeal brushings was feasible but inferior to tissue samples.This study confirms nasopharyngeal brushing as an applicable sampling method that can aid in nucleic acid-based NPC research.

Transcriptome-wide association analysis identified candidate susceptibility genes for nasopharyngeal carcinoma

Dear Editor,Nasopharyngeal carcinoma(NPC)is a common malignancy in East and Southeast Asia,especially in South China.The etiology of NPC has been linked to genetic susceptibility,Epstein-Barr virus(EBV)infection,and environmental factors.Accumulated evidence including multiple genome-wide association studies(GWASs)has revealed robust genetic predisposition of NPC.However,GWAS-identified genetic variants collectively account for only 8.2%of NPC heritability[1].The underlying inherited predisposition is largely undetermined.The strongest genetic signal for NPC consistently hits the human leukocyte antigen(HLA)region on 6p21[2].However,the highly polymorphic nature and complicated long-range linkage disequilibrium(LD)in the HLA region particularly obscure the causal variants driving the association.In addition,most genetic variants located in introns or intergenic regions.The causal genes mediating genetic effects on NPC risk have rarely been ascertained by GWAS alone.