TRIP13通过同源重组通路提高肺腺癌细胞的放射抗性

背景与目的放疗是非小细胞肺癌(non-small cell lung cancer,NSCLC)最常用的治疗手段之一。然而,一部分肿瘤细胞对放射线的不敏感是放疗疗效差、患者预后不良的重要原因之一,探究放射抵抗背后的深层机制是解决这一临床难题的关键。本研究旨在寻找与肺腺癌(lungadenocarcinoma,LUAD)放射抵抗相关的分子,初步经数据库筛选锁定甲状腺素受体结合因子13(thyroid hormone receptor interactor 13,TRIP13)为主要研究对象,并探索TRIP13是否与LUAD的放射抵抗有关及具体机制,以期为临床接受放疗的LUAD患者的联合治疗提供理论依据和潜在靶点。方法选取基因表达综合数据库(Gene Expression Omnibus,GEO)中的GSE18842、GSE19188和GSE33532共3个数据集,借助R 4.1.3软件分别筛选3个数据集中差异表达的基因(|logFC|>1.5,P<0.05),之后使用Venn diagram找出在3个数据集中共有的差异表达基因。随后,借助STRING在线工具和Cytoscape软件,对筛选出来的差异基因进行蛋白质相互作用分析和模块分析,借助Kaplan-Meier Plotter数据库对各基因进行生存预后分析,并确定TRIP13基因作为后续主要研究分子。随后,采用亚致死性剂量照射法对人LUAD细胞系H292进行多次X射线照射,以构建具有放射抗性的细胞系H292DR。采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)实验和克隆形成实验验证H292DR细胞的放射抗性能力。Western blot检测H292细胞和H292DR细胞中TRIP13蛋白的表达水平。使用小干扰RNA(small interfering RNA,siRNA)沉默H292DR细胞中TRIP 13蛋白的表达并进行Western blot检测。观察TRIP13沉默后H292DR细胞的克隆形成能力和迁移能力,随后检测共济失调-毛细血管扩张突变(ataxia telangiectasia mutated,ATM)蛋白等与同源重组密切相关的蛋白的表达水平变化。结果经多个GEO数据集筛选、外部数据集的验证以及生存分析发现,TRIP13在LUAD中高表达,并与接受过放疗的LUAD患者的不良预后有关;并且,TRIP13基因富集分析(gene set enrichment analysis,GSEA)的结果提示,TRIP13可能通过促进放疗后的同源重组修复而与LUAD放射抵抗有密切关联。经实验检测发现,TRIP13的表达在H292DR中上调,而沉默TRIP13后能够增加H292DR细胞对放射线的敏感性。结论TRIP13与接受放疗后的LUAD患者的预后不良有关,可能是通过促进同源重组修复途径来介导LUAD细胞对放射线的抵抗。

Orientation and Decision-Making for Soccer Based on Sports Analytics and AI:A Systematic Review

Due to ever-growing soccer data collection approaches and progressing artificial intelligence(AI) methods, soccer analysis, evaluation, and decision-making have received increasing interest from not only the professional sports analytics realm but also the academic AI research community. AI brings gamechanging approaches for soccer analytics where soccer has been a typical benchmark for AI research. The combination has been an emerging topic. In this paper, soccer match analytics are taken as a complete observation-orientation-decision-action(OODA) loop.In addition, as in AI frameworks such as that for reinforcement learning, interacting with a virtual environment enables an evolving model. Therefore, both soccer analytics in the real world and virtual domains are discussed. With the intersection of the OODA loop and the real-virtual domains, available soccer data, including event and tracking data, and diverse orientation and decisionmaking models for both real-world and virtual soccer matches are comprehensively reviewed. Finally, some promising directions in this interdisciplinary area are pointed out. It is claimed that paradigms for both professional sports analytics and AI research could be combined. Moreover, it is quite promising to bridge the gap between the real and virtual domains for soccer match analysis and decision-making.

Nitrogen‑Doped Magnetic‑Dielectric‑Carbon Aerogel for High‑Efficiency Electromagnetic Wave Absorption

Carbonbased aerogels derived from biomass chitosan are encountering a flourishing moment in electromagnetic protection on account of lightweight,controllable fabrication and versatility.Nevertheless,developing a facile construction method of component design with carbon-based aerogels for high-efficiency electromagnetic wave absorption(EWA)materials with a broad effective absorption bandwidth(EAB)and strong absorption yet hits some snags.Herein,the nitrogen-doped magnetic-dielectric-carbon aerogel was obtained via ice template method followed by carbonization treatment,homogeneous and abundant nickel(Ni)and manganese oxide(MnO)particles in situ grew on the carbon aerogels.Thanks to the optimization of impedance matching of dielectric/magnetic components to carbon aerogels,the nitrogen-doped magnetic-dielectric-carbon aerogel(Ni/MnO-CA)suggests a praiseworthy EWA performance,with an ultra-wide EAB of 7.36 GHz and a minimum reflection loss(RLmin)of−64.09 dB,while achieving a specific reflection loss of−253.32 dB mm−1.Furthermore,the aerogel reveals excellent radar stealth,infrared stealth,and thermal management capabilities.Hence,the high-performance,easy fabricated and multifunctional nickel/manganese oxide/carbon aerogels have broad application aspects for electromagnetic protection,electronic devices and aerospace.

CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules

Background and objective Low-density computed tomography(LDCT)improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data.Hence,accurate diagnosis of early-stage lung cancer remains challenging.The purpose of the study was to assess the feasibility of using circulating tumour cells(CTCs)to differentiate malignant from benign pulmonary nodules.Materials and methods 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited.Peripheral blood samples were collected before surgery,and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis.Laser capture microdissection,MALBAC amplification,and whole-exome sequencing were performed on 8 samples.The diagnostic efficacy of CTCs counting,and the genomic variation profile of benign and malignant CTCs samples were analysed.Results Using 2.5 cells/5 m L as the cut-off value,the area under the receiver operating characteristic curve was of 0.651(95%confidence interval:0.538-0.764),with a sensitivity and specificity of 0.526 and 0.800,respectively,and positive and negative predictive values of 91.1%and 30.3%,respectively.Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples.TP53 mutations were identified in CTCs of four malignant cases;in particular,g.7578115T>C,g.7578645C>T,and g.7579472G>C were exclusively detected in all four malignant samples.Conclusion CTCs play an ancillary role in the diagnosis of pulmonary nodules.TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.

Integrative transcriptomic and metabolomic analyses reveal the flavonoid biosynthesis of Pyrus hopeiensis flowers under cold stress

Low temperature is among the most restrictive factors to limit the yield and distribution of pear. Pyrus hopeiensis is a valuable wild resource.PCA showed that P. hopeiensis had strong cold resistance. In this study, the mRNA and metabolome sequencing of P. hopeiensis flower organs exposed to different low temperatures were performed to identify changes of genes and metabolites in response to low-temperature stress. A total of 4 851 differentially expressed genes(DEGs) were identified. Trend analysis showed that these DEGs were significantly enriched in profiles 19, 18, 7, 14, 1, 4 and 11. And the KEGG enrichment analysis showed that the DEGs in profile 18 were significantly enriched in flavone and flavonol biosynthesis. Besides, the expressed trends as well as GO and KEGG functional enrichment analyses of DEGs under cold and freezing stress showed significantly difference. Analyses of flavonoid-related pathways indicated that flavonoid structural genes had undergone significant changes. Correlation analysis showed that b HLH and MYB TFs may affect flavonoid biosynthesis by regulating structural gene expression. And PhMYB308 and PhMYB330 were likely candidate repressors of flavonoid biosynthesis by binding to a specific site in bHLH proteins. In total, 92 differentially accumulated metabolites(DAMs) were identified in P. hopeiensis flowers including 12 flavonoids. WGCNA results showed that coral 1, pink and brown 4 modules were closely associated with flavonoids and 11 MYBs and 15 bHLHs among the three modules may activate or inhibit the expression of 23 structural genes of flavonoid biosynthesis. Taken together, the results of this study provided a theoretical basis for further exploration of the molecular mechanisms of flavonoid biosynthesis and cold resistance of P. hopeiensis flower organs and our findings laid a foundation for further molecular breeding in cold-resistant pear varieties.

Effects of site conditions on growth and wood properties of Populus×euramericana cv.'74/76'

The growth and wood properties of 240 individual Populus×euramericana cv.’74/76’(hereafter poplar 107)trees planted in Hebei Plain,China was evaluated.Mean annual increments in height,breast height diameter and volume,as well as cellulose,hemicellulose and lignin contents,shrinkage,density,bending strength and modulus of elasticity in the heart wood and sap wood.Environmental factors influencing growth and wood properties were analyzed using correlation and stepwise regres sion.The results show that the coefficients of variation(CVs)of growth traits ranged from 10.6 to 22.4%.The CVs of the chemical properties of heartwood ranged from 4.3 to 30.2%,and for sap wood from 3.2 to 27.5%.The CVs of the physical and mechanical properties of heartwood ranged from 8.6 to 31.7%,and for sapwood from 6.4 to 29.9%.The results of one-way ANOVA showed that there were significant differences in growth traits and wood properties among sites.Soil pH,total and available phosphorus,total potassium,and soil organic matter were key soil factors affecting growth and wood properties of poplar 107,whereas mean annual ground temperatures and precipitation were the main climatic factors.To better cultivate poplar 107,area with less annual rainfall,slightly higher temperature and soil pH value close to neutral should be selected.

Presenilin and Alzheimer’s disease interactions with aging,exercise and high-fat diet:A systematic review

Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases seriously affect the quality of life and longevity of the population and place a huge burden on health care and economic systems around the world.Humans have two types of Psn,presenilin-1(PSEN1)and presenilin-2(PSEN2).Mutations in the genes encoding PSEN1,PSEN2,and amyloid precursor protein(APP)have been identified as the major genetic causes of AD.Psn is a complex gene strongly influenced by genetic and environmental factors.The effects of exercise,training,and a high-fat diet on the Psn gene expressed in the heart and its related pathways are not fully understood.Fortunately,relevant aspects of the mutational effects on Psn can be studied experimentally in easily handled animal models,including Drosophila,mice,and other animals,all of which share orthologous genes of Psn with humans.Many previous studies have linked aging,exercise training,and a high-fat diet to the Psn gene.This review discusses the interrelationship between aging,exercise training,and a high-fat diet on the Psn gene and its associated disease,AD.The aim is to understand the adverse effects of Psn gene mutations on the body and the diseases caused by AD,find ways to alleviate the adverse effects and provide new directions for the improvement of treatment strategies for diseases caused by Psn gene mutations.

不同丙烯腈含量丁腈橡胶在海水中的动静态溶胀行为

通过悬挂式浸泡装置和橡胶冲击试验机考察了3种不同丙烯腈含量的丁腈橡胶(N18、N26和N41)在海水中的动、静态溶胀行为。利用傅里叶变换红外光谱、能量色散谱、场发射扫描电镜对溶胀试件结构和形貌进行了表征,并利用伺服拉力机进行了力学性能测试。通过水溶胀对比试验揭示了海水对橡胶静态溶胀行为的影响,通过冲击试验比较了动、静态溶胀状态下橡胶试件的质量变化率(MCF)。结果表明,与水溶胀行为相比,橡胶在氯化钠溶液中的静态溶胀程度更低,MCF最小值为0.133%来自于N41试件。然而,氯化钠溶液中的离子在橡胶内部扩散使其表面成分发生变化,硬度略微提高,硬度增量的最小值来自于N41试件为0.2 Shore A。动态溶胀试验的MCF值是静态溶胀的2～4倍,最小动态MCF值0.316%同样来自于N41试件。最后,阐述了溶胀对丁腈橡胶力学性能的影响,揭示了冲击与溶胀的相互关系,并探讨了丙烯腈对丁腈橡胶耐溶胀性的作用。

Responses of antioxidant defense system of epilithic mosses to drought stress in karst rock desertified areas

Barbula fallax Hedw., Erythrodontium julaceum(Schwaegr.) Par., and Bryum argenteum Hedw. are typical rock mosses growing on rocks in different terrestrial habitats. In this study, B. fallax and E. julaceum, which are epilithic mosses growing in rock desertification in Guizhou, China, were used as ecophysiological mosses in a combination of field investigations and laboratory experiments. We also investigated the reference moss B. argenteum, which is a widely distributed moss in habitats with soil as substrate. Our research focused on the response of the antioxidant defense system of epilithic mosses to drought stress. Most antioxidant defense indicators increased initially, then declined at later stages of drought stress. In contrast, the carotenoid content increased constantly. In addition, there was an initial increase(albeit variable) in relative membrane permeability, with this parameter showing a parabolic trend in all of the epilithic mosses. Among the three species, E. julaceum demonstrated the strongest resistance followed by B. fallax and then by B. argenteum. The epilithic mosses displayed stronger resistance compared to the native mosses; the increase in O_2 content and other reactive oxygen species(ROS) at the early stage of drought stress induced the enzymatic and non-enzymatic scavenging systems tosequester ROS. Moreover, the radical scavenging ability and strong drought tolerance was maintained. The longterm growth of bryophyte under drought conditions in a karst environment can help eliminate the intense response of mosses to drought stress as they adapt.

The Evolution of a Karst Rocky Desertification Land Ecosystem and Its Driving Forces in the Houzhaihe Area, China

Understanding the evolution of karst rocky desertification (KRD) quantitatively is essential to obtain objective knowledge about the concept of KRD and the form reason of KRD, and is useful to restore KRD land. Houzhaihe area located in central plateau in Guizhou Province was studied here as a representative assemblage landform and its KRD’ s evolution and driving factors were studied, based mainly on high-resolution remote sensing image in 1963, 1978, 2005 and 2010. The KRD land comprises light KRD, moderate KRD and severe KRD. The results demonstrated that the evolution process of KRD can be divided into four modes such as unchanged, weakened, fluctuated and aggravated in the study area. The KRD with no changes from 1963 to 2010, namely, unchanged mode, accounted for 43.76% of the total area of the KRD in 2010;it distributed in the area with the slope of 15&#176 - 25&#176 and >25&#176 basically. Furthermore, the severe KRD distributed mainly in the areas within 300 - 600 m distance from settlement;when the distance away from the rural settlements was more than 900 m, the severe KRD declined, and its proportion was 28.6% and 10.6% in 1963 and 2010 respectively. In the peak-cluster depressions, located in central study area, the slope cropland with slope of 15&#176 - 25&#176 was still abounding, and was seriously rocky desertification generally. So, we propose that the existence of a large number of slope croplands is still the major driving factor of land rocky desertification. Therefore, for the rocky desertification control, the authors consider that the focal point is to alter the land use of steep-slope cropland at present.

Effects of organic mineral fertiliser on heavy metal migration and potential carbon sink in soils in a karst region

Heavy metal pollution in karst mountainous area of Guizhou has spread due to the long-term exploitation of mineral resources and the improper disposal of environmentally hazardous waste. Heavy metals are characterised by non-degradation, strong toxicity, and constant accumulation, posing a grave threat to karst mountain fragile soil ecosystem. To reduce the harm caused by heavy metal pollution and damage to agricultural products, research was undertaken on the basis of previous work by simulating pot experiments on pak choi cabbage(Brassica rapa chinensis)planted in Cd-contaminated soil: different amounts of organic mineral fertilisers(OMF) compared with chemical fertiliser(CF) were used and by detecting the amount of heavy metal in the mature vegetable, a better fertilisation strategy was developed. The results showed that the Cd content in vegetables grown with CF was 23.70 mg/kg,while that of vegetables grown with OMF and bacterial inoculant was the lowest at 15.13 mg/kg. This suggests that the use of OMF and microbes in karst areas not only promotes plant growth but also hinders plant absorption of heavy metal ions in the soil. In addition, through the collection of pot leachate, the detection of water chemistrycharacteristics, and the calculation of the calcite saturation index, it was found that the OMF method also induces certain carbon sink effects. The results provide a new way in which rationalise the use of OMFs in karst areas to alleviate soil heavy metal pollution and increase soil carbon sequestration.

Effects of mineral-organic fertilizer on the biomass of green Chinese cabbage and potential carbon sequestration ability in karst areas of Southwest China

The karst mountain areas of Southwest China contain barren farmland soils and suffer from nutritional and water deficiencies that affect crop productivity. Hence,it is imperative to apply suitable fertilizers to restore soil fertility and maintain crop yield. The aim of this study is to investigate the effects of mineral-organic fertilizer(MOF)made of potassic rock and organic waste on the growth of crops. For this purpose, green Chinese cabbage grown using three different fertilization methods including MOF,inorganic fertilizer(IF), and a control was evaluated. We determined soil water content, agronomic characteristics,and biomass of green Chinese cabbage in different treatments. Furthermore, surface runoff from the pot experiments and soil leachate from pot experiments were collected to determine water temperature, pH, and cation and anion concentrations. The results demonstrate thatMOF can improve the soil water-holding capacity of soil,and the basic agronomic characteristics of the cabbage treated with MOF were superior to those with IF. Using MOF can promote the increase in cabbage biomass.Additionally, the concentration of inorganic carbon(largely in the form of HCO_3^-) in surface runoff water treated by MOF was higher than the other treatments, establishing carbon sequestration potential. This work provides a novel and environmentally friendly fertilization pattern in karst areas, which will improve crop yield and also increase the carbon sequestration potential of crops.

Characteristics and distributions of humic acids in two soil profiles of the southwest China Karst area

Characteristics and distributions of humic acid(HA) and soil organic matter(SOM) in a yellow soil profile and a limestone soil profile of the southwest China Karst area were systematically investigated to reveal their evolutions in different soils of the study area. The results showed that characteristics and distribution of SOM along the two soil profiles were notably different. Total organic carbon(TOC) contents of soil samples decreased just slightly along the limestone soil profile but sharply along the yellow soil profile. TOCs of the limestone soils were significantly higher than those of the corresponding yellow soils, and C/N ratios of SOMs showed a similar variation trend to that of TOCs, indicating that SOM can be better conserved in the limestone soil than in the yellow soil. The soil humic acids were exhaustively extracted and further fractionated according to their apparent molecular weights using ultrafiltration techniques to explore underlying conservation mechanisms. The result showed that C/N ratios of HAs from different limestone soil layers were relatively stable and that large molecular HA fractions predominated the bulk HA of the top soil, indicating that HA in the limestone profile was protected while bio and chemical degradations were retarded. Combined with organic elements contents and mineral contents of two soils, weconcluded that high calcium contents in limestone soils may play a key role in SOM conservation by forming complexation compounds with HAs or/and enclosing SOMs with hypergene CaCO_3 precipitation.

Estimation of soil organic carbon storage and its fractions in a small karst watershed

With few available soil organic carbon(SOC)profiles and the heterogeneity of those that do exist, the estimation of SOC pools in karst areas is highly uncertain.Based on the spatial heterogeneity of SOC content of 23,536 samples in a karst watershed, a modified estimation method was determined for SOC storage that exclusively applies to karst areas. The method is a "soil-type method" based on revised calculation indexes for SOC storage. In the present study, the organic carbon contents of different soil types varied greatly, but generally decreased with increasing soil depth. The organic carbon content decreased nearly linearly to a depth of 0–50 cm and then varied at depths of 50–100 cm. Because of the large spatial variability in the karst area, we were able to determine that influences of the different indexes on the estimation of SOC storage decreased as follows: soil thickness > boulder content > rock fragment content > SOC content > bulk density. Using the modified formula, the SOC content in the Houzhai watershed in Puding was estimated to range from 3.53 to 5.44 kg m^(-2), with an average value of 1.24 kg m^(-2) to a depth of 20 cm, and from 4.44 to 14.50 kg m^(-2), with an average value of 12.12 kg m^(-2) to a depth of 100 cm. The total SOC content was estimated at 5.39*10^(5) t.

Rapid estimation of soil heavy metal nickel content based on optimized screening of near-infrared spectral bands

In near-infrared spectroscopy,the traditional feature band extraction method has certain limitations.Therefore,a band extraction method named the three-step extraction method was proposed.This method combines characteristic absorption bands and correlation coefficients to select characteristic bands corresponding to various spectral forms and then uses stepwise regression to eliminate meaningless variables.Partial least squares regression(PLSR)and extreme learning machine(ELM)models were used to verify the effect of the band extraction method.Results show that the differential transformation of the spectrum can effectively improve the correlation between the spectrum and nickel(Ni)content.Most correlation coefficients were above 0.7 and approximately 20%higher than those of other transformation methods.The model effect established by the feature variable selection method based on comprehensive spectral transformation is only slightly affected by the spectral transformation form.Infive types of spectral transformation,the RPD values of the proposed method were all within the same level.The RPD values of the PLSR model were concentrated between 1.6 and 1.8,and those of the ELM model were between 2.5 and2.9,indicating that this method is beneficial for extracting more complete spectral features.The combination of the three-step extraction method and ELM algorithm can effectively retain important bands associated with the Ni content of the soil.The model based on the spectral band selected by the three-step extraction method has better prediction ability than the other models.The ELM model of the first-order differential transformation has the best prediction accuracy(RP^2=0.923,RPD=3.634).The research results provide some technical support for monitoring heavy metal content spectrum in local soils.

CO flux of soil respiration in natural recovering karst abandoned farmland in Southwest China

To estimate carbon sequestration potential in the karst area,soil respiration in a natural recovering karst abandoned farmland in Shawan,Puding,Guizhou,southwest China was continuously and automatically monitored for more than two years.The results show that the CO2flux of soil respiration(2.63±1.89 lmol m^-2s-^1)is higher in the karst area than in non-karst areas under similar conditions but that regional value(1.32 lmol m-2s-1)is lower because of larger rock fragment coverage(~50%).A the same time,the temperature sensitivity of soil respiration(Q10)in this study area is significantly higher than that of non-karst areas under similar conditions.Soil respiration has an obvious temporal variation,which is reflected in a significant exponential relationship between soil respiration and soil temperature,but the relationship between soil respiration and soil moisture is very complex.Especially soil respiration has an obvious spatial variation,which is likely affected by different diffusion or water-rock reaction processes.

Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model

The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil （Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure） were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system.

Early Age of Onset, Multiple Primary Malignancies and Poor Prognosis Are Indicative of an Inherited Predisposition to Esophageal Squamous Cell Carcinoma in Familial Rather Than Sporadic Disease- An Update Based on 14- to 23-year Follow-up

<正> OBJECTIVE To demonstrate the effects of an inheritedpredisposition to familial esophageal squamous cellcarcinoma (ESCC) through the comparison and analysis of theclinicopathologic differences between familial and sporadic ESCCcases.METHODS Differences in age of onset, prevalence rates ofdouble primary ESCC, and survival rates between familial ESCC (n= 476) and sporadic ESCC cases (n = 1226) were analyzed.RESULTS Overall, familial ESCC cases showed a significantlyyounger age of onset (51.9 ± 8.2 vs. 53.4 ± 8.0, P_(t-test) = 0.00), asignificantly higher prevalence rate for double ESCC (2.73 % vs.1.22%, adjusted with TNM:χ_(MH)~2= 4.029, P = 0.045), and a lowersurvival rate than in sporadic cases (P_(wald) = 0.04). The familial casesshowed both a younger age of onset and poorer survival in mostsubgroups, and the differences were more marked in early-stagerather than in the late-stage disease groups.CONCLUSION Theses findings confirm the existence of familialas opposed to sporadic ESCC. By the theory of the 'two-hit' originof cancer, these findings also suggest that the 'first hit', a geneticpredisposition, can affect the age of onset, number of primarycarcinomas, and the prognosis for familial ESCC patients.