Regulation of TMEM100 expression by epigenetic modification,effects on proliferation and invasion of esophageal squamous carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a prevalent malignancy with a high morbidity and mortality rate.TMEM100 has been shown to be suppressor gene in a variety of tumors,but there are no reports on the role of TMEM100 in esophageal cancer(EC).AIM To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion.METHODS Firstly,we found the expression of TMEM100 in EC through The Cancer Genome Atlas database.The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis.We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification.To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100.Finally,we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases(MAPK)pathway.RESULTS In the present study,by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects.Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC.Then,we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells[quantitative real-time PCR(qRT-PCR)and western blotting].Subsequently,we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells(qRT-PCR and western blotting).Overexpression of TMEM100 also inhibited proliferation,invasion and migration of ESCC cells(cell counting kit-8 and clone formation assays).Next,by enrichment analysis,we found that the gene set was significantly enriched in the MAPK signaling pathway.The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting.CONCLUSION TMEM100 is a suppressor gene in ESCC,and its low expression may lead to aberrant activation of the MAPK pathway.Promoter methylation may play a key role in regulating TMEM100 expression.

Xi-Feng-Hua-Shi granules for diarrhea-predominant irritable bowel syndrome:protocol for a randomized,double-blind,placebo-controlled multi-center clinical trial

Background:Irritable bowel syndrome(IBS)is a common functional bowel disorder that can severely affect the quality of life of patients.Limited drugs have been reported for modern medical IBS treatment.The advantages of traditional Chinese medicine(TCM)treatment are gradually becoming prominent.Xi-Feng-Hua-Shi granules have been clinically used for diarrhea-predominant IBS(IBS-D)treatment for many years in TCM practice.Thus,this study aimed to further verify the effectiveness and safety of Xi-Feng-Hua-Shi(XFHS)granules in IBS-D treatment through a randomized,double-blind,placebo-controlled multi-center clinical trial and provide high-quality evidence for its effectiveness and safety in treatment,as well as provide a basis for clinical rational drug use and explore new clinical IBS-D treatment plans.Methods:A randomized,double-blind,placebo-controlled multi-center clinical trial will be performed in 23 hospitals.A total of 300 participants will be randomly divided into the experimental group(prescribed with XFHS granules)and the control group(prescribed with the placebo granules),with 150 participants in each group.The appearance,shape,color,and taste of the placebo granules are the same as those of XFHS granules.All participants will receive a 4-week treatment and a 6-month follow-up.The primary outcome is the overall clinical efficacy;the secondary outcomes are the IBS-Symptom Severity Score(IBS-SSS),TCM Syndrome Evaluation,and the IBS-Quality of Life(IBS-QoL)score,mental state assessment,and recurrence rate.Outcome measures(including primary and secondary outcome measures)are collected at baseline,as well as 2,4,16,and 28 weeks post-intervention.Discussion:This randomized,placebo-controlled,multi-center trial may provide high-quality evidence for the clinical XFHS granule efficacy in IBS-D treatment.Additionally,this study will conduct safety evaluations to provide a basis for clinical rational drug use.

Effect of seepage on soil arching effect in deep shield tunnel

Shield tunneling and post-tunneling steady seepage are accompanied by stress and displacement variations,which could induce and influence the soil arching effect.Although there are many studies on the tunneling-induced soil arching effect,the research about the effect of seepage on soil arching effect is extremely lacking.In this study,a numerical model is firstly established and verified by field data.Then,a series of numerical models,whose simulation method of steady seepage is verified by adopting the conformal mapping technique,are established to study the soil arching evolution of deep-buried tunneling and post-construction steady seepage.The results indicate that seepage leads to an increase in effective vertical stress,which is consistent with the existing theory.The seepage weakens the soil arching effect resulting in the height of the arch zone reducing from 2.38D(D is the tunnel diameter)to 1.25D.The seepage leads to the further development of ground consolidation settlement,but the differential displacement in the soil mass decreases.The ground reaction curve in the steady seepage condition shows a bigger value than that after excavation.It is reasonable to control the ground loss ratio in the range of 0.5–1.0%,which can minimize overburden pressure with moderate ground deformation.

高铁路基近期研究(英文)

随着高速铁路的快速发展,高铁路基的研究成为一大热点。目前大量的研究工作集中在高铁路基动力响应、工后沉降和长期服役性能。这些工作促进了对高铁路基一般规律的了解,但距准确评价路基在百年服役过程中经受干湿循环、温度变化与动荷载耦合作用下服役性能的改变尚远。本文总结了高铁路基近期的研究成果,并提出了未来的研究方向。

土体含水率时域反射法现场测试经验模型研究（英文）

目的:建立含水率与介电常数间的经验关系模型是利用时域反射(TDR)技术测试土体含水率的关键。通过收集并建立包含45种土样418个试验数据点的数据库,提出一个土体质量含水率与表观介电常数间的经验公式,分析经验公式误差随土体类型、干密度、击实功、孔隙水电导率和温度等因素的变化规律,并提出考虑干密度影响的修正方法。创新点:1.基于电磁波相互作用理论,直接建立土体质量含水率和介电常数间的关系模型;2.通过数据拟合得到通用型经验公式,可在现场无标定快速高效地实现含水率测试。方法:1.通过理论分析,直接建立土体质量含水率和介电常数间的关系模型(公式(9));2.通过试验数据收集和回归分析得到通用型经验公式(图2和公式(10));3.通过影响因素分析,对公式的适用性和有效性进行分析(图3~7)。结论:1.该经验公式对常见的土体类型均能给出误差在±0.05 g/g以内的结果;2.在1.3~2.3 g/cm3的干密度范围内,该经验公式具有较好的适用性;在工程中常见的击实功和孔隙水电导率变化范围内,含水率测试精度可满足工程要求;4~30°C温度变化范围对本经验公式的计算结果无明显影响;3.利用该经验公式,对于特殊场地,可以不通过标定实现TDR现场测试,具有较好的实用性。

Physical model testing in geotechnical engineering

1Introduction Several characteristics of natural soils complicate the relationship between their mechanical behaviour and geotechnical construction and maintenance in the field.These characteristics include the presence of three phases(solid particle,water,and air),particle constitutions of various minerals(such as quartz,kaolinite,and montmorillonite),and an exceptionally wide range of particle size fromμm-scale(clay particles smallerthan2μm)to100-mm scale(suchas somegravelsandpebbles)。