目的:探讨染色体结构维持蛋白1A(structural maintenance of chromosome 1A,SMC1A)在乳腺癌中的表达情况,分析其与临床病理特征的相关性以及对乳腺癌细胞凋亡的影响。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析S...目的:探讨染色体结构维持蛋白1A(structural maintenance of chromosome 1A,SMC1A)在乳腺癌中的表达情况,分析其与临床病理特征的相关性以及对乳腺癌细胞凋亡的影响。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析SMC1A m RNA在乳腺癌及正常乳腺组织中的表达差异及其与乳腺癌预后的相关性。收集南京医科大学第一附属医院2023年1—12月间48例乳腺癌患者手术切除的癌组织和癌旁组织标本,采用实时荧光定量聚合酶链反应和免疫组织化学分析SMC1A的表达,并评估其与患者临床病理指标的关系。通过下调乳腺癌细胞系MCF-7中SMC1A表达,检测其凋亡相关蛋白的变化。结果:对TCGA相关转录组测序数据分析提示,SMC1A m RNA在乳腺癌组织中的表达显著高于正常乳腺组织,并与乳腺癌的预后紧密相关。临床样本验证也表明,SMC1A的表达水平在乳腺癌组织中显著高于癌旁组织,并与TNM分期、淋巴结转移及病理分化程度相关。siRNA介导的SMC1A下调在MCF-7细胞中显著提升了Cleaved-caspase-3、Cleaved-caspase-9及Bax的表达,降低了Bcl2的表达。结论:SMC1A在乳腺癌组织中高表达,并与乳腺癌的进展及病理分化有关。初步机制研究表明,SMC1A的表达调控可能对促进乳腺癌细胞凋亡具有重要作用。展开更多
目的 探讨Cornelia de Lange综合征(Cornelia de Lange syndrome, CdLS)2型双胞胎患儿的临床表型及基因检测结果,明确患儿的致病原因。方法 收集1例CdLS患儿及父母的临床资料,采集外周血进行家系高通量测序分析。结果 患儿具有特殊面容...目的 探讨Cornelia de Lange综合征(Cornelia de Lange syndrome, CdLS)2型双胞胎患儿的临床表型及基因检测结果,明确患儿的致病原因。方法 收集1例CdLS患儿及父母的临床资料,采集外周血进行家系高通量测序分析。结果 患儿具有特殊面容,眉毛浓密,鼻梁高,上唇薄,嘴角下斜。心脏超声提示动脉导管未闭,卵圆孔未闭。凝血及生化检测发现患儿凝血功能异常,低蛋白血症,胆红素升高。遗传代谢病串联质谱筛查未见明显异常;染色体非整倍体分析:染色体组成46,XY,染色体数目正常。家系全外显子组检测发现:患儿、弟弟及母亲均携带SMC1A基因c.897C>G变异,父亲为野生型。参考ACMG变异解读指南,该变异初步判定为可能致病变异。结论 双胞胎均携带SMC1A基因c.897C>G变异位点,该变异为新发变异,扩大了SMC1A基因变异谱,为临床诊断及患儿家系再生育指导提供了重要依据。展开更多
Introduction:Structural maintenance of chromosome 1A(SMC1A)is a crucial compound of the cohesin complex.It has been reported to regulate the epithelial-mesenchymal transition(EMT)process in multiple cancers.Objectives...Introduction:Structural maintenance of chromosome 1A(SMC1A)is a crucial compound of the cohesin complex.It has been reported to regulate the epithelial-mesenchymal transition(EMT)process in multiple cancers.Objectives:The present study aims to further clarify the role of SMC1A in cervical cancer.Methods:We analyzed data from four datasets and confirmed that SMC1A showed high expression in cervical cancer samples and was related to poor prognosis of patients with cervical cancer.Cell proliferation of SiHa and C-33A with knockdown of SMC1A was assessed using CCK-8 and colony formation assay.The migration and invasion were estimated by wound healing assay and Transwell assay separately.The effect of SMC1A on the chemosensitivity of cisplatin and paclitaxel in cervical cancer cells was detected by flow cytometry assay.Results:Results of the immunohistochemistry(IHC)assay confirmed that the expression of SMC1A was increased in tumor tissues.The cell viability was remarkably suppressed in SiHa and C-33A by knocking down the expression of SMC1A.The increase of E-cadherin expression and decrease of N-cadherin and Snail expression verified that inhibition of SMC1A suppressed the EMT process of cervical cancer cells.Further,cell migration,and invasion were significantly repressed by the absence of SMC1A.Cisplatin and paclitaxel are effective chemotherapeutic agents used in the treatment of cervical cancer.Silencing of SMC1A remarkably promoted the apoptosis induced by cisplatin and paclitaxel,revealing that the chemotherapy resistance to cisplatin and paclitaxel in cervical cancer could reduce by knocking down SMC1A.Further,metastasis associated with colon cancer 1(MACC1)was identified as the downstream factor of SMC1A.Its upregulation reversed the proliferation and the EMT process induced by SMC1A silencing.Conclusion:Therefore,our study concluded that SMC1A serves as a therapeutic molecular target to regulate the malignant phenotypes of cervical cancer.展开更多
分析2019年3月遵义医科大学附属医院收治的Cornelia de Lange综合征(CdLs)患儿2例的临床资料及基因变异结果。2例均在婴儿期起病,表现为难治性癫痫,均伴发育落后及特殊外貌,基因检测显示X染色体上SMC1A基因突变,例1为c.2561dupA(p.K854...分析2019年3月遵义医科大学附属医院收治的Cornelia de Lange综合征(CdLs)患儿2例的临床资料及基因变异结果。2例均在婴儿期起病,表现为难治性癫痫,均伴发育落后及特殊外貌,基因检测显示X染色体上SMC1A基因突变,例1为c.2561dupA(p.K854fs)移码突变;例2为c.3441+1G>A(exon24)剪接突变,均为新生杂合突变,位点未见文献报道。2例患儿为SMC1A基因突变所致CdLs,进一步扩大了CdLs的基因型。提示对于早期癫痫起病伴特殊外貌及发育落后的患儿需考虑CdLs的可能,必要时需行基因检测。展开更多
目的分析一例临床表现疑似德朗热综合征的男性患儿的遗传学病因。方法采集患儿的外周血样进行染色体核型分析,基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)检测及全外显子组测序(whole exome sequencing,WES)检测...目的分析一例临床表现疑似德朗热综合征的男性患儿的遗传学病因。方法采集患儿的外周血样进行染色体核型分析,基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)检测及全外显子组测序(whole exome sequencing,WES)检测。同时采集其父母外周血样,对患儿核型、基因组拷贝数、全外显子异常的疑似致病性变异行家系验证。结果患儿临床表现为发育落后、小头畸形、上睑下垂、小颌畸形、低耳位,临床诊断为疑似德朗热综合征(Cornelia de Lange syndrome,CdLS)。其染色体核型分析及CNV-seq检测结果未见异常,全外显子组测序检测显示存在5个杂合变异和1个X染色体半合子变异。根据遗传模式和家系验证结果,SMC1A基因c.3500T>C(p.Ile1167Thr)半合子变异为患儿临床表现的遗传学病因。该变异在dbSNP数据库及gnomAD数据库中未见收录,PolyPhen2,PROVEAN,SIFT软件预测为有害变异,PhastCons保守性预测为保守。ACMG变异分类标准证据支持为PM2、PP2和PP3。结论新发现的SMC1A基因c.3500T>C(p.I1167T)错义变异为患儿临床表现的遗传学病因,该患儿为CdLS综合征Ⅱ型(温和型)。本研究的结果丰富了CdLS综合征Ⅱ型的变异谱,为临床咨询提供了数据支持。展开更多
We study RXTE PCA data for the high mass X-ray binary source SMC X-1 between 2003–10 and 2003–12 when the source was in its high states.The source is found to be frequently bursting which can be seen as flares in li...We study RXTE PCA data for the high mass X-ray binary source SMC X-1 between 2003–10 and 2003–12 when the source was in its high states.The source is found to be frequently bursting which can be seen as flares in lightcurves that occur at a rate of one every 800 s, with an average of 4–5 Type Ⅱ X-ray bursts per hour.We note that typically a burst was short, lasting for a few tens of seconds in addition to a few long bursts spanning more than a hundred seconds that were also observed.The flares apparently occupied 2.5% of the total observing time of 225.5 ks.We note a total of 272 flares with mean FWHM of the flare ～21 s.The rms variability and aperiodic variability are independent of flares.As observed, the pulse profiles of the lightcurves do not change their shape, implying that there is no change in the geometry of an accretion disk due to a burst.The hardness ratio and rms variability of lightcurves exhibit no correlation with the flares.The flare fraction shows a positive correlation with the peak-to-peak ratio of the primary and secondary peaks of the pulse profile.The observed hardening or softening of the spectrum cannot be correlated with the flaring rate but may be due to the interstellar absorption of X-rays as evident from the change in hydrogen column density(n_H).It is found that the luminosity of the source increases with the flaring rate.Considering that the viscous timescale is equal to the mean recurrence time of flares, we fixed the viscosity parameter α ～ 0.16.展开更多
目的对3例Cornelia de Lange综合征(CdLS)患儿的临床表型及基因检测结果进行分析,明确其致病原因。方法选取2020年3月12日、8月14日、12月5日于甘肃省妇幼保健院医学遗传中心就诊的3例CdLS患儿为研究对象。收集患儿及其父母的临床资料,...目的对3例Cornelia de Lange综合征(CdLS)患儿的临床表型及基因检测结果进行分析,明确其致病原因。方法选取2020年3月12日、8月14日、12月5日于甘肃省妇幼保健院医学遗传中心就诊的3例CdLS患儿为研究对象。收集患儿及其父母的临床资料,采集外周血样进行家系高通量测序分析。结果3例患儿的主要临床表现包括发育迟缓、智力低下、特殊面容和其他伴随症状。根据国际诊断共识标准,3例患儿被拟诊为CdLS。通过家系全外显子组测序及生物信息学分析,确诊CdLS。患儿1携带NIPBL基因c.5567_5569delGAAinsTAT错义变异,患儿2携带SMC1A基因c.607A>G错义变异,患儿3携带HDAC8基因c.628+1G>A剪接变异。3例患儿均为新发变异。结论3例患儿均确诊CdLS,并发现了致病基因变异位点,其中NIPBL基因c.5567_5569delGAAinsTAT及HDAC8基因c.628+1G>A变异位点既往未见报道,丰富了CdLS的变异谱。展开更多
文摘目的:探讨染色体结构维持蛋白1A(structural maintenance of chromosome 1A,SMC1A)在乳腺癌中的表达情况,分析其与临床病理特征的相关性以及对乳腺癌细胞凋亡的影响。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析SMC1A m RNA在乳腺癌及正常乳腺组织中的表达差异及其与乳腺癌预后的相关性。收集南京医科大学第一附属医院2023年1—12月间48例乳腺癌患者手术切除的癌组织和癌旁组织标本,采用实时荧光定量聚合酶链反应和免疫组织化学分析SMC1A的表达,并评估其与患者临床病理指标的关系。通过下调乳腺癌细胞系MCF-7中SMC1A表达,检测其凋亡相关蛋白的变化。结果:对TCGA相关转录组测序数据分析提示,SMC1A m RNA在乳腺癌组织中的表达显著高于正常乳腺组织,并与乳腺癌的预后紧密相关。临床样本验证也表明,SMC1A的表达水平在乳腺癌组织中显著高于癌旁组织,并与TNM分期、淋巴结转移及病理分化程度相关。siRNA介导的SMC1A下调在MCF-7细胞中显著提升了Cleaved-caspase-3、Cleaved-caspase-9及Bax的表达,降低了Bcl2的表达。结论:SMC1A在乳腺癌组织中高表达,并与乳腺癌的进展及病理分化有关。初步机制研究表明,SMC1A的表达调控可能对促进乳腺癌细胞凋亡具有重要作用。
文摘目的 探讨Cornelia de Lange综合征(Cornelia de Lange syndrome, CdLS)2型双胞胎患儿的临床表型及基因检测结果,明确患儿的致病原因。方法 收集1例CdLS患儿及父母的临床资料,采集外周血进行家系高通量测序分析。结果 患儿具有特殊面容,眉毛浓密,鼻梁高,上唇薄,嘴角下斜。心脏超声提示动脉导管未闭,卵圆孔未闭。凝血及生化检测发现患儿凝血功能异常,低蛋白血症,胆红素升高。遗传代谢病串联质谱筛查未见明显异常;染色体非整倍体分析:染色体组成46,XY,染色体数目正常。家系全外显子组检测发现:患儿、弟弟及母亲均携带SMC1A基因c.897C>G变异,父亲为野生型。参考ACMG变异解读指南,该变异初步判定为可能致病变异。结论 双胞胎均携带SMC1A基因c.897C>G变异位点,该变异为新发变异,扩大了SMC1A基因变异谱,为临床诊断及患儿家系再生育指导提供了重要依据。
文摘Introduction:Structural maintenance of chromosome 1A(SMC1A)is a crucial compound of the cohesin complex.It has been reported to regulate the epithelial-mesenchymal transition(EMT)process in multiple cancers.Objectives:The present study aims to further clarify the role of SMC1A in cervical cancer.Methods:We analyzed data from four datasets and confirmed that SMC1A showed high expression in cervical cancer samples and was related to poor prognosis of patients with cervical cancer.Cell proliferation of SiHa and C-33A with knockdown of SMC1A was assessed using CCK-8 and colony formation assay.The migration and invasion were estimated by wound healing assay and Transwell assay separately.The effect of SMC1A on the chemosensitivity of cisplatin and paclitaxel in cervical cancer cells was detected by flow cytometry assay.Results:Results of the immunohistochemistry(IHC)assay confirmed that the expression of SMC1A was increased in tumor tissues.The cell viability was remarkably suppressed in SiHa and C-33A by knocking down the expression of SMC1A.The increase of E-cadherin expression and decrease of N-cadherin and Snail expression verified that inhibition of SMC1A suppressed the EMT process of cervical cancer cells.Further,cell migration,and invasion were significantly repressed by the absence of SMC1A.Cisplatin and paclitaxel are effective chemotherapeutic agents used in the treatment of cervical cancer.Silencing of SMC1A remarkably promoted the apoptosis induced by cisplatin and paclitaxel,revealing that the chemotherapy resistance to cisplatin and paclitaxel in cervical cancer could reduce by knocking down SMC1A.Further,metastasis associated with colon cancer 1(MACC1)was identified as the downstream factor of SMC1A.Its upregulation reversed the proliferation and the EMT process induced by SMC1A silencing.Conclusion:Therefore,our study concluded that SMC1A serves as a therapeutic molecular target to regulate the malignant phenotypes of cervical cancer.
文摘分析2019年3月遵义医科大学附属医院收治的Cornelia de Lange综合征(CdLs)患儿2例的临床资料及基因变异结果。2例均在婴儿期起病,表现为难治性癫痫,均伴发育落后及特殊外貌,基因检测显示X染色体上SMC1A基因突变,例1为c.2561dupA(p.K854fs)移码突变;例2为c.3441+1G>A(exon24)剪接突变,均为新生杂合突变,位点未见文献报道。2例患儿为SMC1A基因突变所致CdLs,进一步扩大了CdLs的基因型。提示对于早期癫痫起病伴特殊外貌及发育落后的患儿需考虑CdLs的可能,必要时需行基因检测。
文摘目的分析一例临床表现疑似德朗热综合征的男性患儿的遗传学病因。方法采集患儿的外周血样进行染色体核型分析,基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)检测及全外显子组测序(whole exome sequencing,WES)检测。同时采集其父母外周血样,对患儿核型、基因组拷贝数、全外显子异常的疑似致病性变异行家系验证。结果患儿临床表现为发育落后、小头畸形、上睑下垂、小颌畸形、低耳位,临床诊断为疑似德朗热综合征(Cornelia de Lange syndrome,CdLS)。其染色体核型分析及CNV-seq检测结果未见异常,全外显子组测序检测显示存在5个杂合变异和1个X染色体半合子变异。根据遗传模式和家系验证结果,SMC1A基因c.3500T>C(p.Ile1167Thr)半合子变异为患儿临床表现的遗传学病因。该变异在dbSNP数据库及gnomAD数据库中未见收录,PolyPhen2,PROVEAN,SIFT软件预测为有害变异,PhastCons保守性预测为保守。ACMG变异分类标准证据支持为PM2、PP2和PP3。结论新发现的SMC1A基因c.3500T>C(p.I1167T)错义变异为患儿临床表现的遗传学病因,该患儿为CdLS综合征Ⅱ型(温和型)。本研究的结果丰富了CdLS综合征Ⅱ型的变异谱,为临床咨询提供了数据支持。
文摘We study RXTE PCA data for the high mass X-ray binary source SMC X-1 between 2003–10 and 2003–12 when the source was in its high states.The source is found to be frequently bursting which can be seen as flares in lightcurves that occur at a rate of one every 800 s, with an average of 4–5 Type Ⅱ X-ray bursts per hour.We note that typically a burst was short, lasting for a few tens of seconds in addition to a few long bursts spanning more than a hundred seconds that were also observed.The flares apparently occupied 2.5% of the total observing time of 225.5 ks.We note a total of 272 flares with mean FWHM of the flare ～21 s.The rms variability and aperiodic variability are independent of flares.As observed, the pulse profiles of the lightcurves do not change their shape, implying that there is no change in the geometry of an accretion disk due to a burst.The hardness ratio and rms variability of lightcurves exhibit no correlation with the flares.The flare fraction shows a positive correlation with the peak-to-peak ratio of the primary and secondary peaks of the pulse profile.The observed hardening or softening of the spectrum cannot be correlated with the flaring rate but may be due to the interstellar absorption of X-rays as evident from the change in hydrogen column density(n_H).It is found that the luminosity of the source increases with the flaring rate.Considering that the viscous timescale is equal to the mean recurrence time of flares, we fixed the viscosity parameter α ～ 0.16.
文摘目的对3例Cornelia de Lange综合征(CdLS)患儿的临床表型及基因检测结果进行分析,明确其致病原因。方法选取2020年3月12日、8月14日、12月5日于甘肃省妇幼保健院医学遗传中心就诊的3例CdLS患儿为研究对象。收集患儿及其父母的临床资料,采集外周血样进行家系高通量测序分析。结果3例患儿的主要临床表现包括发育迟缓、智力低下、特殊面容和其他伴随症状。根据国际诊断共识标准,3例患儿被拟诊为CdLS。通过家系全外显子组测序及生物信息学分析,确诊CdLS。患儿1携带NIPBL基因c.5567_5569delGAAinsTAT错义变异,患儿2携带SMC1A基因c.607A>G错义变异,患儿3携带HDAC8基因c.628+1G>A剪接变异。3例患儿均为新发变异。结论3例患儿均确诊CdLS,并发现了致病基因变异位点,其中NIPBL基因c.5567_5569delGAAinsTAT及HDAC8基因c.628+1G>A变异位点既往未见报道,丰富了CdLS的变异谱。
