Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,d...Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,differentiation,migration,and myotube fusion in primary myoblasts and C2C12 cells.To this end,we constructed TNFαmuscle-conditional knockout(TNFα-CKO)mice and compared them with flox mice to assess the effects of TNFαknockout on skeletal muscles.Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development,enhanced regenerative capacity,and improved exercise endurance compared to flox mice,with no significant differences observed in major visceral organs or skeletal structure.Using label-free proteomic analysis,we found that TNFα-CKO altered the distribution of several muscle development-related proteins,such as Hira,Casz1,Casp7,Arhgap10,Gas1,Diaph1,Map3k20,Cfl2,and Igf2,in the nucleus and cytoplasm.Gene set enrichment analysis(GSEA)further revealed that TNFαdeficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling.These findings suggest that TNFα-CKO positively regulates muscle growth and development,possibly via these newly identified targets and pathways.展开更多
BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental factors.It is essential to understand the function of plasma metabolites in...BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental factors.It is essential to understand the function of plasma metabolites in the development of MI and unravel its complex pathogenesis.METHODS This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relationships between plasma metabolites and MI risk.We used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa.In addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabolites)and MI(20,917 individuals with MI and 440,906 individuals without MI)susceptibility.Inverse variance weighted was the primary method for estimating causal effects.MR estimates are expressed as beta coefficients or odds ratio(OR)with 95%CI.RESULTS We identified 14 plasma metabolites associated with the occurrence of MI(P<0.05),among which 8 plasma metabolites[propionylglycine levels(OR=0.922,95%CI:0.881–0.965,P<0.001),gamma-glutamylglycine levels(OR=0.903,95%CI:0.861–0.948,P<0.001),hexadecanedioate(C16-DC)levels(OR=0.941,95%CI:0.911–0.973,P<0.001),pentose acid levels(OR=0.923,95%CI:0.877–0.972,P=0.002),X-24546 levels(OR=0.936,95%CI:0.902–0.971,P<0.001),glycine levels(OR=0.936,95%CI:0.909–0.964,P<0.001),glycine to serine ratio(OR=0.930,95%CI:0.888–0.974,P=0.002),and mannose to trans-4-hydroxyproline ratio(OR=0.912,95%CI:0.869–0.958,P<0.001)]were correlated with a decreased risk of MI,whereas the remaining 6 plasma metabolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR=1.051,95%CI:1.018–1.084,P=0.002),behenoyl dihydrosphingomyelin(d18:0/22:0)levels(OR=1.076,95%CI:1.027–1.128,P=0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR=1.067,95%CI:1.027–1.109,P=0.001),alpha-ketobutyrate levels(OR=1.108,95%CI:1.041–1.180,P=0.001),5-acetylamino-6-formylamino-3-methyluracil levels(OR=1.047,95%CI:1.019–1.076,P<0.001),and N-acetylputrescine to(N(1)+N(8))-acetylspermidine ratio(OR=1.045,95%CI:1.018–1.073,P<0.001)]were associated with an increased risk of MI.Furthermore,we also observed that the mentioned relationships were unaffected by horizontal pleiotropy(P>0.05).On the contrary,MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites(P>0.05 for each comparison).CONCLUSIONS Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI,among which 13 plasma metabolites have not been reported previously.These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets.展开更多
目的:比较曲妥珠单抗和帕妥珠单抗(trastuzumab plus pertuzumab,HP)联合紫杉类+铂类(TCbHP)、紫杉类单药(THP)、蒽环类序贯紫杉类(AC-THP)三种化疗方案在真实世界临床实践中新辅助治疗HER-2阳性乳腺癌的疗效、安全性及耐受性。方法:回...目的:比较曲妥珠单抗和帕妥珠单抗(trastuzumab plus pertuzumab,HP)联合紫杉类+铂类(TCbHP)、紫杉类单药(THP)、蒽环类序贯紫杉类(AC-THP)三种化疗方案在真实世界临床实践中新辅助治疗HER-2阳性乳腺癌的疗效、安全性及耐受性。方法:回顾性分析2019年6月至2021年12月于保定市第一中心医院等河北省共11家三级甲等医院接受三种方案新辅助治疗并完成后续手术的180例HER-2阳性乳腺癌患者的临床病理资料,其中TCbHP组78例、THP组70例、AC-THP组32例,比较三种治疗方案的疗效、安全性及耐受性,并采用统计学方法分析临床病理因素对总体病理完全缓解(total pathologic complete response,tpCR)率的影响。结果:总人群tpCR率为58.9%(106/180)。TCbHP组的tpCR率为64.1%(50/78),高于THP组的54.3%(38/70)和AC-THP组的56.3%(18/32),差异无统计学意义(P=0.454)。TCbHP组的3级及以上不良反应发生率为12.8%(10/78),高于THP组的4.3%(3/70)和AC-THP组的9.4%(3/32),差异无统计学意义(P=0.255)。THP组的既定方案完成率为98.6%(69/70),高于TCbHP组的92.3%(72/78)和AC-THP组的90.6%(29/32),差异无统计学意义(P=0.147)。180例患者中绝经后组与绝经前组的tpCR率分别为65.4%(70/107)与49.3%(36/73),HER-2免疫组织化学法(IHC)3+组与HER-2 IHC2+且荧光原位杂交(FISH)+组的tpCR率分别为65.0%(102/157)与17.4%(4/23),激素受体(HR)阴性组与HR阳性组的tpCR率分别为78.0%(64/82)与42.9%(42/98),白蛋白结合型紫杉醇组与其他紫杉类药物组的tpCR率分别为66.3%(65/98)与50.0%(41/82),组间进行比较差异均具有统计学意义(均P<0.05)。Logistic回归多因素分析表明,HER-2 IHC3+、HR阴性、使用白蛋白结合型紫杉醇为tpCR率的独立影响因素。结论:TCbHP、THP、AC-THP方案新辅助治疗HER-2阳性乳腺癌在真实世界临床实践中疗效确切,安全性及耐受性良好。TCbHP方案可考虑作为HER-2阳性乳腺癌新辅助治疗的优选方案。展开更多
Objective:To explore the expression of CD151 in gastric cancer tissues and its clinical significance.Methods:Immunohistochemistry was employed to detect the expression of CD151 in gastric cancer tissues and adjacent n...Objective:To explore the expression of CD151 in gastric cancer tissues and its clinical significance.Methods:Immunohistochemistry was employed to detect the expression of CD151 in gastric cancer tissues and adjacent normal tissues.The relationship between CD151 expression and the clinicopathological characteristics of gastric cancer was analyzed.Results:The expression of CD151 in gastric cancer tissues was significantly higher than in adjacent normal tissues(P<0.05).It was associated with the degree of differentiation,depth of invasion,lymph node metastasis,and TNM staging of gastric cancer.The survival time of patients with high CD151 expression was significantly shorter than that of those with low expression(P<0.05).Conclusion:High expression of CD151 in gastric cancer tissues is correlated with the malignant biological behavior of gastric cancer and can serve as an indicator for evaluating the prognosis of gastric cancer.展开更多
In order to characterize the features of radium isotopes in estuaries of Tianjin,a continuous survey and sampling of typical estuaries were conducted from 2013 to 2017 in this study.The activities of natural radioacti...In order to characterize the features of radium isotopes in estuaries of Tianjin,a continuous survey and sampling of typical estuaries were conducted from 2013 to 2017 in this study.The activities of natural radioactive radium isotopes(^(223)Ra,^(224)Ra,and ^(228)Ra)in groundwater and surface water were measured by the radium-delayed coincidence counting(RaDeCC)system.The non-conservative behavior of the radium isotopes was investigated under hydrogeochemical conditions and urbanization.The results indicated that in terms of horizontal distribution,the activities of radium in groundwater(Hangu,Tanggu,and Dagang)showed an upward trend from north to south and demonstrated a higher figure than surface water(Haihe River and Duliujian River).Concerning the vertical distribution,the activitives of radium at a 15 m burial depth was higher than that at a 30 m burial depth in all measurements.The activities of radium isotopes in the study area increased with the increase of total dissolved solids,and their desorption behavior on Fe-Mn oxides was constrained by the redox intensity.Different hydrogeological conditions resulted in variations in the vertical profile of radium activities.The activity of radium was regulated by seasonal variation and precipitation in groundwater and surface water.In addition,the rapid urbanization has caused a significant impact on the features of radium isotopes in typical estuaries of Tianjin.Meanwhile,radium isotopes can be applied to reflect the impact of urbanization on surface watergroundwater systems.Clarifying and cleverly utilizing the relationship between behavior of radium isotopes and urbanization will promote the development of the Tianjin Binhai New Area in a healthy way.展开更多
As critical measures to educate and cultivate people’s morality,“Ideology and Politics of Course”has gradually become the focus in actual undergraduate education research in universities.Targeting the single ideolo...As critical measures to educate and cultivate people’s morality,“Ideology and Politics of Course”has gradually become the focus in actual undergraduate education research in universities.Targeting the single ideological and political education mode and students’lack of interest in experimental courses,this paper,through various links,including pre-class preview,in-class teaching,and after-class data analysis,takes the common emitter single tube amplifier experiment as an example to organically integrate the excavated ideological and political elements with practical operation and carry out teaching case design and practice;realize the improvement of students’learning initiative and problem-analysis ability;and achieve the purpose of cultivating people throughout the whole process and in a comprehensive direction.展开更多
基金Xizang Major Science and Technology Project(XZ202101ZD0005N)Yunnan Major Science and Technology Project(202302AE090015)+1 种基金National Key R&D Program of China(2023ZD04044-04)National Natural Science Foundation of China(32060736)。
文摘Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,differentiation,migration,and myotube fusion in primary myoblasts and C2C12 cells.To this end,we constructed TNFαmuscle-conditional knockout(TNFα-CKO)mice and compared them with flox mice to assess the effects of TNFαknockout on skeletal muscles.Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development,enhanced regenerative capacity,and improved exercise endurance compared to flox mice,with no significant differences observed in major visceral organs or skeletal structure.Using label-free proteomic analysis,we found that TNFα-CKO altered the distribution of several muscle development-related proteins,such as Hira,Casz1,Casp7,Arhgap10,Gas1,Diaph1,Map3k20,Cfl2,and Igf2,in the nucleus and cytoplasm.Gene set enrichment analysis(GSEA)further revealed that TNFαdeficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling.These findings suggest that TNFα-CKO positively regulates muscle growth and development,possibly via these newly identified targets and pathways.
基金supported by the Guangxi Natural Science Foundation(No.2020GXNSFDA238007)the Key Research and Development Program of Guangxi(No.2023AB22024)the Chongzuo Science and Technology Bureau Planning Project(No.FA2018026)。
文摘BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental factors.It is essential to understand the function of plasma metabolites in the development of MI and unravel its complex pathogenesis.METHODS This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relationships between plasma metabolites and MI risk.We used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa.In addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabolites)and MI(20,917 individuals with MI and 440,906 individuals without MI)susceptibility.Inverse variance weighted was the primary method for estimating causal effects.MR estimates are expressed as beta coefficients or odds ratio(OR)with 95%CI.RESULTS We identified 14 plasma metabolites associated with the occurrence of MI(P<0.05),among which 8 plasma metabolites[propionylglycine levels(OR=0.922,95%CI:0.881–0.965,P<0.001),gamma-glutamylglycine levels(OR=0.903,95%CI:0.861–0.948,P<0.001),hexadecanedioate(C16-DC)levels(OR=0.941,95%CI:0.911–0.973,P<0.001),pentose acid levels(OR=0.923,95%CI:0.877–0.972,P=0.002),X-24546 levels(OR=0.936,95%CI:0.902–0.971,P<0.001),glycine levels(OR=0.936,95%CI:0.909–0.964,P<0.001),glycine to serine ratio(OR=0.930,95%CI:0.888–0.974,P=0.002),and mannose to trans-4-hydroxyproline ratio(OR=0.912,95%CI:0.869–0.958,P<0.001)]were correlated with a decreased risk of MI,whereas the remaining 6 plasma metabolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR=1.051,95%CI:1.018–1.084,P=0.002),behenoyl dihydrosphingomyelin(d18:0/22:0)levels(OR=1.076,95%CI:1.027–1.128,P=0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR=1.067,95%CI:1.027–1.109,P=0.001),alpha-ketobutyrate levels(OR=1.108,95%CI:1.041–1.180,P=0.001),5-acetylamino-6-formylamino-3-methyluracil levels(OR=1.047,95%CI:1.019–1.076,P<0.001),and N-acetylputrescine to(N(1)+N(8))-acetylspermidine ratio(OR=1.045,95%CI:1.018–1.073,P<0.001)]were associated with an increased risk of MI.Furthermore,we also observed that the mentioned relationships were unaffected by horizontal pleiotropy(P>0.05).On the contrary,MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites(P>0.05 for each comparison).CONCLUSIONS Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI,among which 13 plasma metabolites have not been reported previously.These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets.
文摘Objective:To explore the expression of CD151 in gastric cancer tissues and its clinical significance.Methods:Immunohistochemistry was employed to detect the expression of CD151 in gastric cancer tissues and adjacent normal tissues.The relationship between CD151 expression and the clinicopathological characteristics of gastric cancer was analyzed.Results:The expression of CD151 in gastric cancer tissues was significantly higher than in adjacent normal tissues(P<0.05).It was associated with the degree of differentiation,depth of invasion,lymph node metastasis,and TNM staging of gastric cancer.The survival time of patients with high CD151 expression was significantly shorter than that of those with low expression(P<0.05).Conclusion:High expression of CD151 in gastric cancer tissues is correlated with the malignant biological behavior of gastric cancer and can serve as an indicator for evaluating the prognosis of gastric cancer.
基金The National Natural Science Foundation of China under contract No.42172273.
文摘In order to characterize the features of radium isotopes in estuaries of Tianjin,a continuous survey and sampling of typical estuaries were conducted from 2013 to 2017 in this study.The activities of natural radioactive radium isotopes(^(223)Ra,^(224)Ra,and ^(228)Ra)in groundwater and surface water were measured by the radium-delayed coincidence counting(RaDeCC)system.The non-conservative behavior of the radium isotopes was investigated under hydrogeochemical conditions and urbanization.The results indicated that in terms of horizontal distribution,the activities of radium in groundwater(Hangu,Tanggu,and Dagang)showed an upward trend from north to south and demonstrated a higher figure than surface water(Haihe River and Duliujian River).Concerning the vertical distribution,the activitives of radium at a 15 m burial depth was higher than that at a 30 m burial depth in all measurements.The activities of radium isotopes in the study area increased with the increase of total dissolved solids,and their desorption behavior on Fe-Mn oxides was constrained by the redox intensity.Different hydrogeological conditions resulted in variations in the vertical profile of radium activities.The activity of radium was regulated by seasonal variation and precipitation in groundwater and surface water.In addition,the rapid urbanization has caused a significant impact on the features of radium isotopes in typical estuaries of Tianjin.Meanwhile,radium isotopes can be applied to reflect the impact of urbanization on surface watergroundwater systems.Clarifying and cleverly utilizing the relationship between behavior of radium isotopes and urbanization will promote the development of the Tianjin Binhai New Area in a healthy way.
基金This paper was supported by the 2021 School-Level Education Reform Project of Hainan Tropical Ocean University Fund(RHYjg2021sz03).
文摘As critical measures to educate and cultivate people’s morality,“Ideology and Politics of Course”has gradually become the focus in actual undergraduate education research in universities.Targeting the single ideological and political education mode and students’lack of interest in experimental courses,this paper,through various links,including pre-class preview,in-class teaching,and after-class data analysis,takes the common emitter single tube amplifier experiment as an example to organically integrate the excavated ideological and political elements with practical operation and carry out teaching case design and practice;realize the improvement of students’learning initiative and problem-analysis ability;and achieve the purpose of cultivating people throughout the whole process and in a comprehensive direction.
