Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to iden...Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.展开更多
In traumatic brain injury, absent in melanoma 2(AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain...In traumatic brain injury, absent in melanoma 2(AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day(post-injury time points) groups. Sham-operated rats only received laminectomy at T9 without contusive injury. Western blot assay revealed that the expression levels of AIM2 were not significantly different among the 1-hour, 6-hour and 1-day groups. The expression levels of AIM2 were markedly higher in the 1-hour, 6-hour and 1-day groups compared with the sham, 3-day and 7-day groups. Double immunofluorescence staining demonstrated that AIM2 was expressed by NeuN+(neurons), GFAP+(astrocytes), CNPase+(oligodendrocytes) and CD11 b+(microglia) cells in the sham-operated spinal cord. In rats with spinal cord injury, AIM2 was also found in CD45+(leukocytes) and CD68+(activated microglia/macrophages) cells in the spinal cord at all time points. These findings indicate that AIM2 is mainly expressed in neurons, astrocytes, microglia and oligodendrocytes in the normal spinal cord, and that after spinal cord injury, its expression increases because of the infiltration of leukocytes and the activation of astrocytes and microglia/macrophages.展开更多
For severe cubital tunnel syndrome, patients with absent sensory nerve action potential tend to have more severe nerve damage than those without. Thus, it is speculated that such patients generally have a poor prognos...For severe cubital tunnel syndrome, patients with absent sensory nerve action potential tend to have more severe nerve damage than those without. Thus, it is speculated that such patients generally have a poor prognosis. How absent sensory nerve action potential affects surgical outcomes remains uncertain owing to a scarcity of reports and conflicting results. This retrospective study recruited one hundred and fourteen cases(88 patients with absent sensory nerve action potential and 26 patients with present sensory nerve action potential) undergoing either subcutaneous transposition or in situ decompression. The minimum follow-up was set at 2 years. Primary outcome measures of overall hand function included their McGowan grade, modified Bishop score, and Disabilities of the Arm, Shoulder, and Hand Questionnaire(DASH) score. For patients with absent sensory nerve action potential, 71 cases(80.7%) achieved at least one McGowan grade improvement, 76 hands(86.4%) got good or excellent results according to the Bishop score, and the average DASH score improved 49.5 points preoperatively to 13.1 points postoperatively. When compared with the present sensory nerve action potential group, they showed higher postoperative McGowan grades and DASH scores, but there was no statistical difference between the modified Bishop scores of the two groups. Following in situ decompression or subcutaneous transposition, great improvement in hand function was achieved for severe cubital tunnel syndrome patients with absent sensory nerve action potential. The functional outcomes after surgery for severe cubital tunnel syndrome are worse in patients with absent sensory nerve action potential than those without. This study was approved by the Ethical Committee of Huashan Hospital, Fudan University, China(approval No. 2017142).展开更多
Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interfe...Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.展开更多
The famous American writer MarkTwain was well—known for his absent-mind-edness.One day,when he was riding in a train,the conductor asked him for his ticket.MarkTwain looked for the ticket in all his pockets.but 11e d...The famous American writer MarkTwain was well—known for his absent-mind-edness.One day,when he was riding in a train,the conductor asked him for his ticket.MarkTwain looked for the ticket in all his pockets.but 11e didn’t find it.At last,the展开更多
Absent pulmonary valve is a rare congenital anomaly, characterized with a dysplastic or absent pulmonary valve tissue and severe pulmonary regurgitation. It is usually associated with tetralogy of Fallot （TOF）. A 7-...Absent pulmonary valve is a rare congenital anomaly, characterized with a dysplastic or absent pulmonary valve tissue and severe pulmonary regurgitation. It is usually associated with tetralogy of Fallot （TOF）. A 7-year-old girl with absent pulmonary valve, pulmonary artery aneurysm and tetralogy of Fallot without cyanosis was operated and 10 months followed up result was reported展开更多
Background:The acute myeloid leukemia 1(AML1)-eight-twenty-one(ETO)fusion protein generated by the t(8;21)(q22;q22)translocation is considered to display a crucial role in leukemogenesis in AML.By focusing on the anti...Background:The acute myeloid leukemia 1(AML1)-eight-twenty-one(ETO)fusion protein generated by the t(8;21)(q22;q22)translocation is considered to display a crucial role in leukemogenesis in AML.By focusing on the anti-leukemia effects of eyes absent 4(EYA4)gene on AML cells,we investigated the biologic and molecular mechanism associated with AML 1-ETO expressed in t(8;21)AML.Methods:Qualitative polymerase chain reaction(PCR),quantitative reverse transcription PCR(RT-PCR),and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines.Different plasmids(including mutant plasmids)of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4.Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4.Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region.The influence ofEYA4 gene in the cell proliferation,apoptosis,and cell clone-forming ability was detected by the technique of Cell Counting Kit-8,flow cytometry,and clonogenic assay.Results:EYA4 gene was hyperrnethylated in AMLI-ETO+patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells,compared to HL-60 and SKNO-1-siA/E cells,respectively.We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA 4 gene by binding at AML 1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases.Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AMLI-ETO cell lines.We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control,respectively.Conclusions:Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene.In addition,we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML 1-ETO+t(8;21)AML.展开更多
Background The prognosis of tetralogy of Fallot with absent pulmonary valve (TOF/APV) without operation is poor. We evaluated the surgical outcome of TOF/APV in a single center. Methods Twenty-two TOF/APV patients und...Background The prognosis of tetralogy of Fallot with absent pulmonary valve (TOF/APV) without operation is poor. We evaluated the surgical outcome of TOF/APV in a single center. Methods Twenty-two TOF/APV patients underwent complete surgical correction in our hospital. Right ventricular outflow tract reconstruction was performed using bovine jugular vein (BJV)-valved conduit implantation (n=10), homograft-valved conduit implantation (n=2), or monocusp-valve patch (n=10). Health-related quality of life (QOL) was evaluated during follow-up. Results The overall survival at 5 and 10 years was 86.4±7.3% (confidence interval 69.4–97.2%). The survival rates were significantly different between patients with and without bronchial stenosis (40 and 100%, P=0.0003, log-rank test). The survival of patients aged>6 months was higher than those≤6 months (100 vs. 40%, P=0.0003, log-rank test). Patients with BJV-valved conduits had higher systolic gradients from the right ventricle to the pulmonary artery (RV–PA) compared to those with monocusp-valve patches. BJV-valved conduit implantation was a risk factor for post-operative pulmonary-valve stenosis. The QOL score for patients with BJV-valved conduits was lower than those with monocusp-valve patches (P<0.05). No reoperation was performed during follow-up. Conclusions Bronchial stenosis and lower age (≤6 months) were the main factors influencing post-operative survival. The use of a BJV-valved conduit was a main reason for RV–PA restenosis;thus, the use of a BJV-valved conduit may increase the need for repeat intervention and decrease the post-operative quality of life.展开更多
Background:Emerging evidence indicates that the sineoculis homeobox homolog 1−eyes absent homolog 1(SIX1–EYA1)transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the...Background:Emerging evidence indicates that the sineoculis homeobox homolog 1−eyes absent homolog 1(SIX1–EYA1)transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes,such as cell-cycle progression and metastasis.However,the roles of the SIX1–EYA1 transcriptional complex and its targets in colorectal cancer(CRC)are still being investigated.This study aimed to investigate the roles of SIX1–EYA1 in the pathogenesis of CRC,to screen inhibitors disrupting the SIX1–EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues(collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine,West China Hospital of Sichuan University,between 2016 and 2018,n=24).In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1–EYA1 interaction.Cell proliferation,cell survival,and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay,clonogenic assay,and Boyden chamber assay,respectively.The Amplified Luminescent Proximity Homogeneous Assay Screen(AlphaScreen)method was used to obtain small molecules that specifically disrupted SIX1–EYA1 interaction.CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts,and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues(for SIX1,7.47±3.54 vs.1.88±0.35,t=4.92,P=0.008;for EYA1,7.61±2.03 vs.2.22±0.45,t=6.73,P=0.005).The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1(CCNA1)and transforming growth factor beta 1(TGFB1)by binding to the myocyte enhancer factor 3 consensus.Knockdown of both SIX1 and EYA1 could decrease cell proliferation,cell invasion,tumor growth,and in vivo tumor growth(all P<0.01).Two small molecules,NSC0191 and NSC0933,were obtained using AlphaScreen and they could significantly inhibit the SIX1–EYA1 interaction with a half-maximal inhibitory concentration(IC50)of 12.60±1.15μmol/L and 83.43±7.24μmol/L,respectively.Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1,causing the pathogenesis of CRC.Pharmacological inhibition of the SIX1–EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.展开更多
MicroRNAs （miRNAs） can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples （tis...MicroRNAs （miRNAs） can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples （tissue, serum, peripheral blood mononuelear cells or other body fluids） differ significantly even in the same patient and therefore have their own specificity for the presented condition. Complex profiles of deregulated miRNAs are of high interest, whereas the importance of non-expressed miRNAs was ignored. Since miRNAs regulate gene expression rather negatively, absent miRNAs could indicate genes with unaltered expression that therefore are normally expressed in specific compartments or under specific disease situations. For the first time, non-detectable miRNAs in different tissues and body fluids from patients with different diseases （cardiomyopathies, Alzheimer＇s disease, bladder cancer, and ocular cancer） were analyzed and compared in this study, miRNA expression data were generated by microarray or TaqMan PCR-based platforms. Lists of absent miRNAs of primarily cardiac patients （myocardium, blood cells, and serum） were clustered and analyzed for potentially involved pathways using two prediction platforms, i.e., miRNA enrichment analysis and annotation tool （miEAA） and DIANA miRPath. Extensive search in biomedical publication databases for the relevance of non-expressed miRNAs in predicted pathways revealed no evidence for their involvement in heart-related pathways as indicated by software tools, confirming proposed approach.展开更多
文摘Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.
基金supported by the National Natural Science Foundation of China,No.81772321(to HZL),81571194(to HZL),81471277(to JGH)a grant from the Key Program of Anhui Province for Outstanding Talents in Universities in China,No.gxbjZD2016071(to HZL),2014H012(to HZL)
文摘In traumatic brain injury, absent in melanoma 2(AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day(post-injury time points) groups. Sham-operated rats only received laminectomy at T9 without contusive injury. Western blot assay revealed that the expression levels of AIM2 were not significantly different among the 1-hour, 6-hour and 1-day groups. The expression levels of AIM2 were markedly higher in the 1-hour, 6-hour and 1-day groups compared with the sham, 3-day and 7-day groups. Double immunofluorescence staining demonstrated that AIM2 was expressed by NeuN+(neurons), GFAP+(astrocytes), CNPase+(oligodendrocytes) and CD11 b+(microglia) cells in the sham-operated spinal cord. In rats with spinal cord injury, AIM2 was also found in CD45+(leukocytes) and CD68+(activated microglia/macrophages) cells in the spinal cord at all time points. These findings indicate that AIM2 is mainly expressed in neurons, astrocytes, microglia and oligodendrocytes in the normal spinal cord, and that after spinal cord injury, its expression increases because of the infiltration of leukocytes and the activation of astrocytes and microglia/macrophages.
基金supported by the National Natural Science Foundation of China,No.81371374(to ZD)
文摘For severe cubital tunnel syndrome, patients with absent sensory nerve action potential tend to have more severe nerve damage than those without. Thus, it is speculated that such patients generally have a poor prognosis. How absent sensory nerve action potential affects surgical outcomes remains uncertain owing to a scarcity of reports and conflicting results. This retrospective study recruited one hundred and fourteen cases(88 patients with absent sensory nerve action potential and 26 patients with present sensory nerve action potential) undergoing either subcutaneous transposition or in situ decompression. The minimum follow-up was set at 2 years. Primary outcome measures of overall hand function included their McGowan grade, modified Bishop score, and Disabilities of the Arm, Shoulder, and Hand Questionnaire(DASH) score. For patients with absent sensory nerve action potential, 71 cases(80.7%) achieved at least one McGowan grade improvement, 76 hands(86.4%) got good or excellent results according to the Bishop score, and the average DASH score improved 49.5 points preoperatively to 13.1 points postoperatively. When compared with the present sensory nerve action potential group, they showed higher postoperative McGowan grades and DASH scores, but there was no statistical difference between the modified Bishop scores of the two groups. Following in situ decompression or subcutaneous transposition, great improvement in hand function was achieved for severe cubital tunnel syndrome patients with absent sensory nerve action potential. The functional outcomes after surgery for severe cubital tunnel syndrome are worse in patients with absent sensory nerve action potential than those without. This study was approved by the Ethical Committee of Huashan Hospital, Fudan University, China(approval No. 2017142).
基金supported by the Gusu Medical Key Talent Project of Suzhou City of China(GSWS2020005)the New Pharmaceutics and Medical Apparatuses Project of Suzhou City of China(SLJ2021007)+3 种基金the Suzhou City Key Clinical Disease Diagnosis and Treatment Technology Special Project,China(LCZX202129)Wujiang Science and Educational Health Revitalization Fund Project,Suzhou,China(WWK202015)the Scientific Research Project of Suzhou Ninth People’s Hospital,Suzhou,China(YK202008)and Suzhou“Science and Education”Youth Science and Technology Project,Suzhou,China(KJXW2020075).
文摘Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.
文摘The famous American writer MarkTwain was well—known for his absent-mind-edness.One day,when he was riding in a train,the conductor asked him for his ticket.MarkTwain looked for the ticket in all his pockets.but 11e didn’t find it.At last,the
基金supported by grants National Distinguished Youth Science Fund (No.30525020)
文摘Absent pulmonary valve is a rare congenital anomaly, characterized with a dysplastic or absent pulmonary valve tissue and severe pulmonary regurgitation. It is usually associated with tetralogy of Fallot （TOF）. A 7-year-old girl with absent pulmonary valve, pulmonary artery aneurysm and tetralogy of Fallot without cyanosis was operated and 10 months followed up result was reported
文摘Background:The acute myeloid leukemia 1(AML1)-eight-twenty-one(ETO)fusion protein generated by the t(8;21)(q22;q22)translocation is considered to display a crucial role in leukemogenesis in AML.By focusing on the anti-leukemia effects of eyes absent 4(EYA4)gene on AML cells,we investigated the biologic and molecular mechanism associated with AML 1-ETO expressed in t(8;21)AML.Methods:Qualitative polymerase chain reaction(PCR),quantitative reverse transcription PCR(RT-PCR),and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines.Different plasmids(including mutant plasmids)of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4.Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4.Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region.The influence ofEYA4 gene in the cell proliferation,apoptosis,and cell clone-forming ability was detected by the technique of Cell Counting Kit-8,flow cytometry,and clonogenic assay.Results:EYA4 gene was hyperrnethylated in AMLI-ETO+patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells,compared to HL-60 and SKNO-1-siA/E cells,respectively.We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA 4 gene by binding at AML 1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases.Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AMLI-ETO cell lines.We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control,respectively.Conclusions:Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene.In addition,we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML 1-ETO+t(8;21)AML.
基金The study was supported by the National Natural Science Foundation of China(81400242 and 81525002)from ESW and HZ,and Program for Distinguished Professor in PUMC from HZ.
文摘Background The prognosis of tetralogy of Fallot with absent pulmonary valve (TOF/APV) without operation is poor. We evaluated the surgical outcome of TOF/APV in a single center. Methods Twenty-two TOF/APV patients underwent complete surgical correction in our hospital. Right ventricular outflow tract reconstruction was performed using bovine jugular vein (BJV)-valved conduit implantation (n=10), homograft-valved conduit implantation (n=2), or monocusp-valve patch (n=10). Health-related quality of life (QOL) was evaluated during follow-up. Results The overall survival at 5 and 10 years was 86.4±7.3% (confidence interval 69.4–97.2%). The survival rates were significantly different between patients with and without bronchial stenosis (40 and 100%, P=0.0003, log-rank test). The survival of patients aged>6 months was higher than those≤6 months (100 vs. 40%, P=0.0003, log-rank test). Patients with BJV-valved conduits had higher systolic gradients from the right ventricle to the pulmonary artery (RV–PA) compared to those with monocusp-valve patches. BJV-valved conduit implantation was a risk factor for post-operative pulmonary-valve stenosis. The QOL score for patients with BJV-valved conduits was lower than those with monocusp-valve patches (P<0.05). No reoperation was performed during follow-up. Conclusions Bronchial stenosis and lower age (≤6 months) were the main factors influencing post-operative survival. The use of a BJV-valved conduit was a main reason for RV–PA restenosis;thus, the use of a BJV-valved conduit may increase the need for repeat intervention and decrease the post-operative quality of life.
基金supported by the grant from scientific research fund of the Science and Technology Department of Sichuan Province(Nos.2017SZ0151 and 2018SZ0113).
文摘Background:Emerging evidence indicates that the sineoculis homeobox homolog 1−eyes absent homolog 1(SIX1–EYA1)transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes,such as cell-cycle progression and metastasis.However,the roles of the SIX1–EYA1 transcriptional complex and its targets in colorectal cancer(CRC)are still being investigated.This study aimed to investigate the roles of SIX1–EYA1 in the pathogenesis of CRC,to screen inhibitors disrupting the SIX1–EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues(collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine,West China Hospital of Sichuan University,between 2016 and 2018,n=24).In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1–EYA1 interaction.Cell proliferation,cell survival,and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay,clonogenic assay,and Boyden chamber assay,respectively.The Amplified Luminescent Proximity Homogeneous Assay Screen(AlphaScreen)method was used to obtain small molecules that specifically disrupted SIX1–EYA1 interaction.CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts,and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues(for SIX1,7.47±3.54 vs.1.88±0.35,t=4.92,P=0.008;for EYA1,7.61±2.03 vs.2.22±0.45,t=6.73,P=0.005).The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1(CCNA1)and transforming growth factor beta 1(TGFB1)by binding to the myocyte enhancer factor 3 consensus.Knockdown of both SIX1 and EYA1 could decrease cell proliferation,cell invasion,tumor growth,and in vivo tumor growth(all P<0.01).Two small molecules,NSC0191 and NSC0933,were obtained using AlphaScreen and they could significantly inhibit the SIX1–EYA1 interaction with a half-maximal inhibitory concentration(IC50)of 12.60±1.15μmol/L and 83.43±7.24μmol/L,respectively.Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1,causing the pathogenesis of CRC.Pharmacological inhibition of the SIX1–EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.
基金supported by grants from the German Research Foundation, the Transregional Collaborative Research Centre (Inflammatory Cardiomyopathy–Molecular Pathogenesis and Therapy) [SFB/TR19]the Federal Ministry of Education and Research for the Small and Medium-sized Enterprises Innovative Program (Grant No. 616 0315296) of Germany
文摘MicroRNAs （miRNAs） can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples （tissue, serum, peripheral blood mononuelear cells or other body fluids） differ significantly even in the same patient and therefore have their own specificity for the presented condition. Complex profiles of deregulated miRNAs are of high interest, whereas the importance of non-expressed miRNAs was ignored. Since miRNAs regulate gene expression rather negatively, absent miRNAs could indicate genes with unaltered expression that therefore are normally expressed in specific compartments or under specific disease situations. For the first time, non-detectable miRNAs in different tissues and body fluids from patients with different diseases （cardiomyopathies, Alzheimer＇s disease, bladder cancer, and ocular cancer） were analyzed and compared in this study, miRNA expression data were generated by microarray or TaqMan PCR-based platforms. Lists of absent miRNAs of primarily cardiac patients （myocardium, blood cells, and serum） were clustered and analyzed for potentially involved pathways using two prediction platforms, i.e., miRNA enrichment analysis and annotation tool （miEAA） and DIANA miRPath. Extensive search in biomedical publication databases for the relevance of non-expressed miRNAs in predicted pathways revealed no evidence for their involvement in heart-related pathways as indicated by software tools, confirming proposed approach.
