Objective Current autosomal short tandem repeat(STR)assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles(CHM),with a maternal genotype serving as an es...Objective Current autosomal short tandem repeat(STR)assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles(CHM),with a maternal genotype serving as an essential reference for comparative analysis.However,their application in pathology represents a challenge because of deficiency or contamination of maternal-origin tissues.This study aimed to develop a novel STR genotyping method for identifying CHM genotypes without a maternal component.Methods Samples with the pathologic description of molar pregnancy were collected.Routine hematoxylin–eosin(HE)staining and p57 immunohistochemistry staining were conducted in accordance with standard guidelines.A novel 26-plex system was explored to classify CHM and diploid pregnancies.The system combined 22 STRs on chromosomes 21/18/13/X,3 sex loci,and 1 quality control marker(TAF9L),enabling molecular diagnosis in the absence of maternal tissue.At last,traditional DNA typing based on villi and decidua(maternal component)of each case was used for result consistency analysis.Results CHM and nonmolar abortus could not be distinguished by the basic HE staining with no fetal evidence or other prominent features.DNA typing was successfully processed for all cases according to the novel 26-plex and traditional system.CHM(46XX)diagnosis required single A-STR/X-STR peaks and absent Y-chromosome markers,excluding chromosomal abnormalities via TAF9L analysis.When the villous tissue analysis revealed single peaks at X-STR/SRY loci,a 1:1 amelogenin ratio,and a 2:1 TAF9L peak ratio,these results overlapped with those of 46XY hydropic abortus or CHM.Notably,p57 immunohistochemical staining resolved the ambiguity.Consistency with traditional DNA genotyping confirmed system accuracy.This multiplex assay enhanced reliability in mole diagnosis,supporting clinical differentiation and genetic counseling.Conclusion This study presents a rapid and cost-effective assay for the genotypic identification of CHM without the need for a maternal component.The method combined the characteristics of STR loci distributed across different chromosomes and developed the clinic application of forensic biomarkers.展开更多
Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was...Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.展开更多
In China,approximately 13% of people living with human immunodeficiency virus(HIV)(PLWH)are receiving lopinavir/ritonavir(LPV/r)-based regimens.These PLWH typically have a history of either treatment failure or intole...In China,approximately 13% of people living with human immunodeficiency virus(HIV)(PLWH)are receiving lopinavir/ritonavir(LPV/r)-based regimens.These PLWH typically have a history of either treatment failure or intolerance to first-line efavirenz-based regimens.Given the considerable pill burden and adverse effects associated with LPV/r,treatment optimization is important for this population.This multicenter retrospective study aimed to evaluate the efficacy and safety of switching from LPV/r-based regimens to the single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide(BIC/FTC/TAF).Virological suppression rates(HIV-RNA<40 copies/mL)were primarily compared between the 48-week periods before and after switching to BIC/FTC/TAF.CD4 counts and metabolic data were also assessed.A total of 461 PLWH were recruited between January 2021 and December 2023,with 92.2% being male,a median age of 38 years,and a median antiretroviral therapy duration of 8 years.Prior to initiating LPV/r,23.0%(106/461)had documented virological failure.During LPV/r treatment,18.9%(20/106)of these individuals experienced viral rebound.Among all participants,the overall virological suppression rates significantly increased from 94.6%(pre-switch)to 98.6%(post-switch)(P<0.001).Notably,among participants with prior virological failure,suppression rates improved significantly from 81.1%to 97.2%(P<0.001),whereas no significant difference was observed in those without such history(from 98.6% to 99.2%,P=0.764).The median triglyceride level decreased from 2.4 mmol/L to 1.8 mmol/L(P<0.001),while no difference in CD4 counts was observed.These findings demonstrate that BIC/FTC/TAF is an effective and metabolically favorable treatment option for PLWH switching from LPV/r based regimens,regardless of whether they have a prior history of virological failure.展开更多
基金supported by the Key Research and Development Program of Shaanxi(No.S2024-YF-YB-SF-1359).
文摘Objective Current autosomal short tandem repeat(STR)assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles(CHM),with a maternal genotype serving as an essential reference for comparative analysis.However,their application in pathology represents a challenge because of deficiency or contamination of maternal-origin tissues.This study aimed to develop a novel STR genotyping method for identifying CHM genotypes without a maternal component.Methods Samples with the pathologic description of molar pregnancy were collected.Routine hematoxylin–eosin(HE)staining and p57 immunohistochemistry staining were conducted in accordance with standard guidelines.A novel 26-plex system was explored to classify CHM and diploid pregnancies.The system combined 22 STRs on chromosomes 21/18/13/X,3 sex loci,and 1 quality control marker(TAF9L),enabling molecular diagnosis in the absence of maternal tissue.At last,traditional DNA typing based on villi and decidua(maternal component)of each case was used for result consistency analysis.Results CHM and nonmolar abortus could not be distinguished by the basic HE staining with no fetal evidence or other prominent features.DNA typing was successfully processed for all cases according to the novel 26-plex and traditional system.CHM(46XX)diagnosis required single A-STR/X-STR peaks and absent Y-chromosome markers,excluding chromosomal abnormalities via TAF9L analysis.When the villous tissue analysis revealed single peaks at X-STR/SRY loci,a 1:1 amelogenin ratio,and a 2:1 TAF9L peak ratio,these results overlapped with those of 46XY hydropic abortus or CHM.Notably,p57 immunohistochemical staining resolved the ambiguity.Consistency with traditional DNA genotyping confirmed system accuracy.This multiplex assay enhanced reliability in mole diagnosis,supporting clinical differentiation and genetic counseling.Conclusion This study presents a rapid and cost-effective assay for the genotypic identification of CHM without the need for a maternal component.The method combined the characteristics of STR loci distributed across different chromosomes and developed the clinic application of forensic biomarkers.
基金supported by the 2022 Natural Science Foundation of Fujian Province(No.2022J011486).
文摘Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.
基金supported by the Capital's Funds for Health Improvement and Research(CFH2024-2-2175).
文摘In China,approximately 13% of people living with human immunodeficiency virus(HIV)(PLWH)are receiving lopinavir/ritonavir(LPV/r)-based regimens.These PLWH typically have a history of either treatment failure or intolerance to first-line efavirenz-based regimens.Given the considerable pill burden and adverse effects associated with LPV/r,treatment optimization is important for this population.This multicenter retrospective study aimed to evaluate the efficacy and safety of switching from LPV/r-based regimens to the single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide(BIC/FTC/TAF).Virological suppression rates(HIV-RNA<40 copies/mL)were primarily compared between the 48-week periods before and after switching to BIC/FTC/TAF.CD4 counts and metabolic data were also assessed.A total of 461 PLWH were recruited between January 2021 and December 2023,with 92.2% being male,a median age of 38 years,and a median antiretroviral therapy duration of 8 years.Prior to initiating LPV/r,23.0%(106/461)had documented virological failure.During LPV/r treatment,18.9%(20/106)of these individuals experienced viral rebound.Among all participants,the overall virological suppression rates significantly increased from 94.6%(pre-switch)to 98.6%(post-switch)(P<0.001).Notably,among participants with prior virological failure,suppression rates improved significantly from 81.1%to 97.2%(P<0.001),whereas no significant difference was observed in those without such history(from 98.6% to 99.2%,P=0.764).The median triglyceride level decreased from 2.4 mmol/L to 1.8 mmol/L(P<0.001),while no difference in CD4 counts was observed.These findings demonstrate that BIC/FTC/TAF is an effective and metabolically favorable treatment option for PLWH switching from LPV/r based regimens,regardless of whether they have a prior history of virological failure.
