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...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.展开更多
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 o...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.展开更多
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-induce...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.展开更多
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 presen...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)。展开更多
1 Introduction Completely decomposed granite(CDG)is widely distributed in South China(Xu et al.,2022;Wang et al.,2023).The parent granite rock mass gradually loses features during the weathering process,and thus needs...1 Introduction Completely decomposed granite(CDG)is widely distributed in South China(Xu et al.,2022;Wang et al.,2023).The parent granite rock mass gradually loses features during the weathering process,and thus needs to be reinforced when used(Lan et al.,2003;Dassekpo et al.,2017;Alamanis et al.,2021).On the other hand,considering the huge demand for construction materials and limited natural resources,it is increasingly important to fully utilize solid waste(Gruhler et al.,2019;Anagnostopoulos et al.,2020;Jiang et al.,2022,2023a,2023b).With high strength and environment-friendly characteristics,incineration bottom ash(IBA)seems to be a suitable reinforcement material for CDG(Ahmed and Khalid,2011;Alhassan and Tankó,2012;Toraldo et al.,2013;Lynn et al.,2017;Xuan et al.,2018;Tang et al.,2020).展开更多
文摘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.
基金supported by National Administration of Traditional Chinese Medicine:2019 Project of building evidence based practice capacity for TCM(No.ZZ13-042-2,No.2019XZZX-XH007)the Jiangsu Administration of traditional Chinese Medicine(No.JD2019SZXZD04).
文摘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.
基金supported by the National Natural Science Foundation of China(Grant Nos.52090082,51938005,52122807,and 52108318)China Hunan Provincial Science&Technology Department(Grant Nos.2021RC3043 and 2021JJ30119).
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.51225804,U1234204,51178418,and 51222803)the Research Fund by China Railway Corporation(No.2014G006)
基金the Research Grants Council(RGC)of Hong Kong Special Administrative Region Government(HKSARG)of China(Nos.15217220,15220221,15226822,and N_Poly U534/20)。
文摘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)。
基金supported by the National Natural Science Foundation of China(Nos.52378341,51938005,and 52090082)the Research Project of Research Centre for Resources Engineering Towards Carbon Neutrality(RCRE)(No.BBEM)of The Hong Kong Polytechnic University,China.
文摘1 Introduction Completely decomposed granite(CDG)is widely distributed in South China(Xu et al.,2022;Wang et al.,2023).The parent granite rock mass gradually loses features during the weathering process,and thus needs to be reinforced when used(Lan et al.,2003;Dassekpo et al.,2017;Alamanis et al.,2021).On the other hand,considering the huge demand for construction materials and limited natural resources,it is increasingly important to fully utilize solid waste(Gruhler et al.,2019;Anagnostopoulos et al.,2020;Jiang et al.,2022,2023a,2023b).With high strength and environment-friendly characteristics,incineration bottom ash(IBA)seems to be a suitable reinforcement material for CDG(Ahmed and Khalid,2011;Alhassan and Tankó,2012;Toraldo et al.,2013;Lynn et al.,2017;Xuan et al.,2018;Tang et al.,2020).