Background： The acute myeloid leukemia 1 （AML1）-eight-twenty-one （ETO） fusion protein generated by the t（8;2 1）（q22;q22） translocation is considered to display a crucial role in leukemogenesis in AML. By focu...Background： The acute myeloid leukemia 1 （AML1）-eight-twenty-one （ETO） fusion protein generated by the t（8;2 1）（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
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
BACKGROUND Unroofed coronary sinus(UCS)is a rare subtype of atrial septal defect.It is frequently associated with a persistent left superior vena cava and is often part of a more intricate cardiac malformation.CASE SU...BACKGROUND Unroofed coronary sinus(UCS)is a rare subtype of atrial septal defect.It is frequently associated with a persistent left superior vena cava and is often part of a more intricate cardiac malformation.CASE SUMMARY This report describes a rare case of an adolescent patient with UCS featuring atrial situs solitus,absence of the right superior vena cava and a persistent left superior vena cava draining into the left atrium consistent with total unroofing of the coronary sinus.This was associated with concurrent severe mitral insufficiency secondary to redundant and prolapsing leaflets,and a substantial left-to-right shunt across the coronary sinus orifice.A comprehensive examination of the existing literature is included,shedding light on the diagnostic challenges of UCS and describing the available surgical options within the context of mitral valve surgery.CONCLUSION UCS is a complex condition requiring careful consideration of associated anomalies and a tailored surgical approach.展开更多
Background:Our previous studies demonstrated that eyes absent homolog 4(EYA4),a member of the eye devel-opment-related EYA family in Drosophila,is frequently methylated and silenced in hepatocellular carcinoma(HCC)spe...Background:Our previous studies demonstrated that eyes absent homolog 4(EYA4),a member of the eye devel-opment-related EYA family in Drosophila,is frequently methylated and silenced in hepatocellular carcinoma(HCC)specimens and associated with shorter survival.The current work aimed to explore the mechanisms through which EYA4 functions as a tumor suppressor in HCC.Methods:Stable EYA4-expressing plasmid(pEYA4)transfectants of the human HCC cell lines Huh-7 and PLC/PRF/5(PLC)were established.Xenografts tumors were established via subcutaneous injection of the stable transfectants into BALB/c nude mice.Tissue samples were obtained from 75 pathologically diagnosed HCC patients.Quantitative real-time polymerase chain reaction,Western blotting and immunohistochemistry were performed to determine the expression of EYA4 in cell lines,xenografts and clinical specimens.The cell proliferation,colony formation,invasiveness and tumor formation of stable transfectants were studied.A gene expression microarray was utilized to screen genes regulated by EYA4 expression.The effect of EYA4 on nuclear factor-κB(NF-κB)/RAS-related protein 1(RAP1)signaling was demonstrated through the co-transfection of pEYA4 and Flag-tagged RAS-related protein 1A gene-expressing plasmid(Flag-RAP1A),functional studies,chromatin immunoprecipitation,immunofluorescence staining and cellular ubiquitination assay.Results:The restoration of EYA4 expression in HCC cell lines suppressed cell proliferation,inhibited clonogenic outgrowth,reduced cell invasion and restrained xenograft tumor growth,and Flag-RAP1A reversed the suppressive effects of pEYA4 in vitro.Activation of NF-κB with tumor necrosis factor-α(TNF-α)increased the binding of p65 to the RAP1A gene promoter and up-regulated RAP1 protein expression.The inhibition of NF-κB with BAY 11-7085 and p65 siRNA successfully blocked TNF-α-induced RAP1 up-regulation.EYA4 antagonized the TNF-α-induced phosphoryla-tion and ubiquitination of inhibitor of NF-κBα(IκBα)as well as the nuclear translocati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 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
Cholecystectomy is the most common digestive tract surgery performed worldwide and injury to the bile duct leads to both acute and chronic sequelae. The incidence of bile duct injury is increased in the presence of se...Cholecystectomy is the most common digestive tract surgery performed worldwide and injury to the bile duct leads to both acute and chronic sequelae. The incidence of bile duct injury is increased in the presence of severe inflammation and is compounded by congenital abnormalities of the biliary tract. Congenitally absent cystic duct is one such rare anomaly with significant surgical implications. So far only nine clear cases of congenitally absent cystic duct have been reported. In this report we describe two additional cases of a congenitally absent cystic duct and provide a comprehensive discussion of the clinical significance, and appropriate surgical management of this anomaly.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
文摘Background： The acute myeloid leukemia 1 （AML1）-eight-twenty-one （ETO） fusion protein generated by the t（8;2 1）（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
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 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BACKGROUND Unroofed coronary sinus(UCS)is a rare subtype of atrial septal defect.It is frequently associated with a persistent left superior vena cava and is often part of a more intricate cardiac malformation.CASE SUMMARY This report describes a rare case of an adolescent patient with UCS featuring atrial situs solitus,absence of the right superior vena cava and a persistent left superior vena cava draining into the left atrium consistent with total unroofing of the coronary sinus.This was associated with concurrent severe mitral insufficiency secondary to redundant and prolapsing leaflets,and a substantial left-to-right shunt across the coronary sinus orifice.A comprehensive examination of the existing literature is included,shedding light on the diagnostic challenges of UCS and describing the available surgical options within the context of mitral valve surgery.CONCLUSION UCS is a complex condition requiring careful consideration of associated anomalies and a tailored surgical approach.
基金supported by National Natural Science Foundation of China(Grant Number 81472261)Natural Science Foundation of Guangdong Province(Grant Numbers 2014A030310033 and 2015A030313032)+1 种基金Science and Technology Planning Project of Guangdong Province(Grant Number 2013B021800122)Science and Technology Planning Projects of Guangzhou City(Grant Number 201604020044).
文摘Background:Our previous studies demonstrated that eyes absent homolog 4(EYA4),a member of the eye devel-opment-related EYA family in Drosophila,is frequently methylated and silenced in hepatocellular carcinoma(HCC)specimens and associated with shorter survival.The current work aimed to explore the mechanisms through which EYA4 functions as a tumor suppressor in HCC.Methods:Stable EYA4-expressing plasmid(pEYA4)transfectants of the human HCC cell lines Huh-7 and PLC/PRF/5(PLC)were established.Xenografts tumors were established via subcutaneous injection of the stable transfectants into BALB/c nude mice.Tissue samples were obtained from 75 pathologically diagnosed HCC patients.Quantitative real-time polymerase chain reaction,Western blotting and immunohistochemistry were performed to determine the expression of EYA4 in cell lines,xenografts and clinical specimens.The cell proliferation,colony formation,invasiveness and tumor formation of stable transfectants were studied.A gene expression microarray was utilized to screen genes regulated by EYA4 expression.The effect of EYA4 on nuclear factor-κB(NF-κB)/RAS-related protein 1(RAP1)signaling was demonstrated through the co-transfection of pEYA4 and Flag-tagged RAS-related protein 1A gene-expressing plasmid(Flag-RAP1A),functional studies,chromatin immunoprecipitation,immunofluorescence staining and cellular ubiquitination assay.Results:The restoration of EYA4 expression in HCC cell lines suppressed cell proliferation,inhibited clonogenic outgrowth,reduced cell invasion and restrained xenograft tumor growth,and Flag-RAP1A reversed the suppressive effects of pEYA4 in vitro.Activation of NF-κB with tumor necrosis factor-α(TNF-α)increased the binding of p65 to the RAP1A gene promoter and up-regulated RAP1 protein expression.The inhibition of NF-κB with BAY 11-7085 and p65 siRNA successfully blocked TNF-α-induced RAP1 up-regulation.EYA4 antagonized the TNF-α-induced phosphoryla-tion and ubiquitination of inhibitor of NF-κBα(IκBα)as well as the nuclear translocati
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
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).
文摘Cholecystectomy is the most common digestive tract surgery performed worldwide and injury to the bile duct leads to both acute and chronic sequelae. The incidence of bile duct injury is increased in the presence of severe inflammation and is compounded by congenital abnormalities of the biliary tract. Congenitally absent cystic duct is one such rare anomaly with significant surgical implications. So far only nine clear cases of congenitally absent cystic duct have been reported. In this report we describe two additional cases of a congenitally absent cystic duct and provide a comprehensive discussion of the clinical significance, and appropriate surgical management of this anomaly.
文摘为探究Ash2l(absent,small,or homeotic 2-like,Ash2l)对小鼠大脑皮质神经祖细胞(neural progenitor cells,NPCs)的增殖能力和细胞周期的影响。本研究利用NPCs标志物PAX6和TBR2,检测NPCs数量和分布的改变情况。结果显示,Ash2l敲除导致NPCs数量显著减少(P<0.05),且分布紊乱。对E16.5小鼠进行在体30 min EdU标记实验,检测NPCs增殖能力,Ash2l敲除导致30 min EdU几乎无法进入NPCs(P<0.001)。结果表示,NPCs增殖能力受到严重的影响。用细胞周期M期标志物pH3,检测大脑皮质中处于M期的NPCs分布情况,同时提取了E16.5小鼠大脑皮质蛋白质,检测细胞周期蛋白A的表达量。Ash2l敲除的NPCs的M期细胞核分布紊乱,G_(2)期标志蛋白质细胞周期蛋白A表达量减少。利用EdU和BrdU双标记法,计算NPCs的S期长度。Ash2l敲除后的NPCs的S期长度缩短(P<0.05)。因此,Ash2l调控NPCs细胞周期进程,进而影响NPCs的增殖能力,敲除小鼠大脑皮质发育异常。本研究强调了表观遗传调控对胚胎期神经系统发育的重要作用,并对表型进行了深入探索。
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.
