目的分析血清血管性血友病因子特异性裂解酶(a disintegrin-like and metalloprotease with thrombospondin type1 motif,member 13,ADAMTS13)水平与接受体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)治疗患者的预后关系。...目的分析血清血管性血友病因子特异性裂解酶(a disintegrin-like and metalloprotease with thrombospondin type1 motif,member 13,ADAMTS13)水平与接受体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)治疗患者的预后关系。方法本研究选取2020年1月—2022年6月在湖南医药学院第一附属医院接受ECMO治疗的42例患者,按照ECMO撤离1个月内预后分为生存组(n=29)和死亡组(n=13)。通过分析接受ECMO治疗患者的血清ADAMTS13水平,分析血清ADAMTS13与接受ECMO治疗患者的预后。结果生存组年龄小于死亡组(P<0.001)。2组性别和体表面积比较,差异无统计学意义(P>0.05)。生存组平均动脉压为(54.24±5.81)mmHg、氧合指数为(178.84±29.38)mmHg,均高于死亡组的(52.56±4.42)mmHg、(155.71±23.12)mmHg;生存组急性生理与慢性健康评分(acute physiology and chronic health evaluation-Ⅱ,APACHE-Ⅱ)评分为(22.51±2.62)分,低于生存组的(27.35±3.85)分(P<0.05)。2组左室射血分数和ECMO流量比较,差异无统计学意义(P>0.05)。ECMO治疗后,2组血清ADAMTS13水平升高。生存组ECMO治疗前1 h及治疗后24 h、48 h血清ADAMTS13水平高于死亡组,差异有统计学意义(P<0.001)。ECMO治疗48 h后血清ADAMTS13水平为ECMO辅助治疗患者死亡的独立危险因素(P<0.001)。结论接受ECMO治疗患者的血清ADAMTS13水平降低与预后不佳相关。展开更多
目的探讨Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin type1 motifs,ADAMTS)基因多态性与脑梗死体检患者颈动脉粥样硬化性斑块易损性及阿托伐他汀降脂疗效的相关性。方法收...目的探讨Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin type1 motifs,ADAMTS)基因多态性与脑梗死体检患者颈动脉粥样硬化性斑块易损性及阿托伐他汀降脂疗效的相关性。方法收集2016年1月至2019年1月河北医科大学第一医院收治的684例脑梗死体检患者的临床资料,根据颈动脉超声检查结果分为稳定斑块组(338例)和易损斑块组(346例)。比较2组患者的一般资料、生化检测指标、ADAMTS rs402007(G/C)位点基因型及等位基因频率。采用Logistic回归分析探讨颈动脉粥样硬化性斑块易损性的危险因素和ADAMTS基因多态性与危险因素在颈动脉粥样硬化性斑块易损性中的交互作用。比较不同基因型患者阿托伐他汀降脂疗效,分析不同基因型与阿托伐他汀疗效的相关性。结果稳定斑块组和易损斑块组糖尿病比例及低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、总胆固醇(total cholesterol,TC)、同型半胱氨酸(homocysteine,HCY)、纤维蛋白原(fibrinogen,FIB)水平的比较差异有统计学意义(P<0.05)。2组患者间GG基因型与GC+CC基因型分布的比较差异有统计学意义(P<0.05)。糖尿病、LDL-C、HCY、FIB是影响颈动脉粥样硬化性斑块易损性的危险因素(P<0.05)。LDL-C与ADAMTS基因rs402007位点存在交互作用(P<0.05)。GG、GC、CC基因型组阿托伐他汀降脂治疗有效率分别为144例(82.29%)、209例(84.27%)、233例(89.27%)。各基因型患者阿托伐他汀治疗前后血脂水平比较差异有统计学意义(P<0.05)。稳定斑块组和易损斑块组治疗前、治疗后LDL-C水平,以及治疗后高密度脂蛋白胆固醇、甘油三酯、TC水平比较差异有统计学意义(P<0.05)。以GG基因型为参考,GC基因型与阿托伐他汀治疗的疗效无相关性(P>0.05),CC基因型与疗效有相关性(P<0.05)。结论ADAMTS基因多态性与颈动脉粥样硬化性斑块易损性存在相关性,与阿托伐他汀的降脂疗效存在相关。展开更多
目的检测含血小板反应蛋白19型基序的解聚素样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motif 19,ADAMTS19)在子宫内膜癌(endometrial cancer,EC)中的表达情况,并探讨ADAMTS19对子宫内膜癌Ishikawa细胞生...目的检测含血小板反应蛋白19型基序的解聚素样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motif 19,ADAMTS19)在子宫内膜癌(endometrial cancer,EC)中的表达情况,并探讨ADAMTS19对子宫内膜癌Ishikawa细胞生物学功能及其意义。方法免疫组化(IHC)和实时荧光定量聚合酶链反应(qRT-PCR)检测子宫内膜癌组织和癌旁组织中ADAMTS19蛋白表达水平及mRNA相对表达水平;分析ADAMTS19表达水平与子宫内膜癌患者临床特征的相关性;体外使用si-RNA沉默Ishikawa细胞中ADAMTS19的表达,qRT-PCR检测其沉默效率,研究细胞增殖、迁移及侵袭能力,蛋白印迹法检测p-STAT3蛋白的表达水平。结果IHC和qRT-PCR结果表明:与癌旁组织相比,子宫内膜癌组织中ADAMTS19表达明显降低(IHC:P<0.001;qRT-PCR:P<0.001);ADAMTS19的低表达与淋巴结转移(P=0.022)、FIGO分期较晚(Ⅲ+Ⅳ期,P=0.025)及肿瘤组织分化程度(P=0.004)密切相关;体外细胞实验表明,与阴性对照组相比,沉默ADAMTS19组Ishikawa细胞的增殖、迁移和侵袭能力明显增强,差异具有统计学意义(增殖:P<0.001,迁移:P<0.05,侵袭:P<0.001)。沉默ADAMTS19组中p-STAT3蛋白的表达水平明显增强(P<0.05)。结论ADAMTS19在子宫内膜癌组织中呈低表达,且与子宫内膜恶性临床特征密切相关,可能是通过促进磷酸化STAT3的表达促进肿瘤细胞增殖、迁移和侵袭能力。ADAMTS19有望成为子宫内膜癌潜在的分子靶标。展开更多
【目的】基于PI3K/Akt通路研究含凝血酶敏感素基序的去解联金属蛋白酶1(a disintegrin and metalloproteinase with thrombospondin motifs 1,ADAMTS1)在产双胎和单胎蒙古羊发情周期不同阶段卵巢内的表达规律,探究ADAMTS1基因影响蒙古...【目的】基于PI3K/Akt通路研究含凝血酶敏感素基序的去解联金属蛋白酶1(a disintegrin and metalloproteinase with thrombospondin motifs 1,ADAMTS1)在产双胎和单胎蒙古羊发情周期不同阶段卵巢内的表达规律,探究ADAMTS1基因影响蒙古羊繁殖性状的作用机制。【方法】选取经产2次的双胎和单胎蒙古羊共40只,自然发情,确定母羊发情期和间情期,分为双胎发情期、双胎间情期、单胎发情期和单胎间情期组,每组各10只羊。利用注射器抽取2~3岁蒙古羊颗粒细胞,分为对照组和试验组,对照组不添加药物,试验组添加15μmol/L LY294002处理颗粒细胞,分别在24、48和72 h测定细胞活力。通过实时荧光定量PCR技术检测母羊卵巢组织和颗粒细胞内ADAMTS1、PI3K、PTEN、Akt、RPS6、Bcl-2和BAX基因的相对表达量;通过Western blotting技术检测卵巢和颗粒细胞内ADAMTS1、PI3K和Akt蛋白的表达丰度。【结果】实时荧光定量PCR结果显示,双胎发情期组ADAMTS1、Bcl-2基因表达量均显著高于其余各组(P<0.05);双胎发情期组和双胎间情期组PI3K、Akt和PTEN基因表达量均显著高于单胎发情期组和单胎间情期组(P<0.05);单胎间情期组RPS6基因表达量显著低于其余各组(P<0.05);间情期与发情期相比,BAX基因表达显著上调(P<0.05)。Western blotting结果显示,双胎发情期ADAMST1蛋白表达量显著高于其余各组(P<0.05);双胎组与单胎组相比,PI3K和Akt蛋白均表达上调,其中,双胎发情期和双胎间情期PI3K蛋白表达量均显著高于单胎发情期组和单胎间情期组(P<0.05),双胎间情期Akt蛋白表达量最高,显著高于其余各组(P<0.05)。与对照组相比,试验组蒙古羊颗粒细胞形态异常,细胞增殖缓慢,且ADAMTS1、PI3K和Akt基因和蛋白的相对表达量均显著降低(P<0.05)。【结论】ADAMTS1、PI3K和Akt基因和蛋白在蒙古羊卵巢和颗粒细胞内的表达趋势一致,呈正向相关关系,证明ADAMTS1基因PI3K/Akt轴在蒙古羊产双胎性状中发挥重要作用。展开更多
Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to...Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.展开更多
Background: ADAMTS(a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic canc...Background: ADAMTS(a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma(PDAC). Methods: We used several databases to analyze the ADAMTS family and then screen out the hub genes. The expression of ADAMTS12 in 106 pairs of PDAC tumors and adjacent normal tissues was examined by immunohistochemistry, and its correlations with clinical parameters were further analyzed. The impacts of ADAMTS12 on the migration of PDAC cells were predicted by gene set enrichment analysis and confirmed by transwell assays. The potential impacts of ADAMTS12 on the epithelial-mesenchymal transition(EMT) were identified by database analysis and experimental proof of real-time quantitative polymerase chain reaction(q PCR) and Western blotting. Results: Our study found that ADAMTS12 was a crucial gene in PDAC, and it was highly expressed in tumor tissues when compared to that in the adjacent tissues. ADATMS12 had predictive value of a poor prognosis for PDAC. The elevation of ADAMTS12 was parallel to the progression of PDAC. Inhibition of ADAMTS12 suppressed the migration of PDAC cells and interfered with the process of EMT. Conclusions: ADAMTS12 is a crucial member of ADAMTSs in PDAC and a predictor of poor prognosis. Additionally, based on its impacts on migration and metastasis in PDAC and the relationship with EMT, ADAMTS12 plays a role of an oncogene in PDAC and may be a promising target for treatment.展开更多
AIM: To explore the phenotype and genotype of WeillMarchesani syndrome(WMS) in a Chinese family and review related literature.METHODS: Three WMS patients and other unaffected individuals in this family with a history ...AIM: To explore the phenotype and genotype of WeillMarchesani syndrome(WMS) in a Chinese family and review related literature.METHODS: Three WMS patients and other unaffected individuals in this family with a history of consanguineous marriage were included in this study. Medical history, comprehensive ophthalmic examinations, and systemic evaluation, as well as whole exome and Sanger sequencing of specific genomic regions, were performed. RESULTS: The three affected siblings presented with short stature, brachydactyly and ocular disorders, including very shallow anterior chamber, high myopia, microspherophakia lens subluxation with stretched zonules and glaucoma. Genetic analysis verified a homozygous missense mutation(c.2983C>T: p. Arg995Trp) in ADAMTS17,which was correlated with the diseases in this family, indicating an autosomal recessive inherited manner of WMS. This review aims to summarize the mutation sites of WMS genes, so as to prevent the disease and better guide clinical diagnosis and treatment.CONCLUSION: A novel homozygous missense variant of ADAMTS17 is identified in a WMS family with a history of consanguineous marriage. Our study expands the range of mutations associated with WMS and deepens our understanding of pathology in disease associated with ADAMTS17 variants.展开更多
BACKGROUND Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels.Congenital lymphangiectasia can affect various organ syste...BACKGROUND Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels.Congenital lymphangiectasia can affect various organ systems;however,it frequently occurs in the lungs accompanied with unexplained pleural effusion.Further,it might not be diagnosed during prenatal examination owing to the absence of pronounced abnormalities.However,after birth the newborn rapidly develops respiratory distress that quickly deteriorates.Genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of this disease.We report a rare case of heterozygous mutation of ADAMTS3 and FLT4 genes,which have not been reported previously.CASE SUMMARY We analysed the case of a neonate who had presented with only pleural effusion at a late gestational age and eventually died due to its inability to establish spontaneous breathing after birth.An autopsy revealed lymphangiectasia of the organ systems.Further,whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes,ADAMTS3 and FLT4,and Sanger verification revealed similar lesions in the mother with no symptoms.CONCLUSION Considering the presented case,obstetricians should observe unexplained foetal pleural effusion,and perform pathology analysis and whole exome sequencing for a conclusive diagnosis and prompt treatment.展开更多
文摘目的分析血清血管性血友病因子特异性裂解酶(a disintegrin-like and metalloprotease with thrombospondin type1 motif,member 13,ADAMTS13)水平与接受体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)治疗患者的预后关系。方法本研究选取2020年1月—2022年6月在湖南医药学院第一附属医院接受ECMO治疗的42例患者,按照ECMO撤离1个月内预后分为生存组(n=29)和死亡组(n=13)。通过分析接受ECMO治疗患者的血清ADAMTS13水平,分析血清ADAMTS13与接受ECMO治疗患者的预后。结果生存组年龄小于死亡组(P<0.001)。2组性别和体表面积比较,差异无统计学意义(P>0.05)。生存组平均动脉压为(54.24±5.81)mmHg、氧合指数为(178.84±29.38)mmHg,均高于死亡组的(52.56±4.42)mmHg、(155.71±23.12)mmHg;生存组急性生理与慢性健康评分(acute physiology and chronic health evaluation-Ⅱ,APACHE-Ⅱ)评分为(22.51±2.62)分,低于生存组的(27.35±3.85)分(P<0.05)。2组左室射血分数和ECMO流量比较,差异无统计学意义(P>0.05)。ECMO治疗后,2组血清ADAMTS13水平升高。生存组ECMO治疗前1 h及治疗后24 h、48 h血清ADAMTS13水平高于死亡组,差异有统计学意义(P<0.001)。ECMO治疗48 h后血清ADAMTS13水平为ECMO辅助治疗患者死亡的独立危险因素(P<0.001)。结论接受ECMO治疗患者的血清ADAMTS13水平降低与预后不佳相关。
文摘目的检测含血小板反应蛋白19型基序的解聚素样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motif 19,ADAMTS19)在子宫内膜癌(endometrial cancer,EC)中的表达情况,并探讨ADAMTS19对子宫内膜癌Ishikawa细胞生物学功能及其意义。方法免疫组化(IHC)和实时荧光定量聚合酶链反应(qRT-PCR)检测子宫内膜癌组织和癌旁组织中ADAMTS19蛋白表达水平及mRNA相对表达水平;分析ADAMTS19表达水平与子宫内膜癌患者临床特征的相关性;体外使用si-RNA沉默Ishikawa细胞中ADAMTS19的表达,qRT-PCR检测其沉默效率,研究细胞增殖、迁移及侵袭能力,蛋白印迹法检测p-STAT3蛋白的表达水平。结果IHC和qRT-PCR结果表明:与癌旁组织相比,子宫内膜癌组织中ADAMTS19表达明显降低(IHC:P<0.001;qRT-PCR:P<0.001);ADAMTS19的低表达与淋巴结转移(P=0.022)、FIGO分期较晚(Ⅲ+Ⅳ期,P=0.025)及肿瘤组织分化程度(P=0.004)密切相关;体外细胞实验表明,与阴性对照组相比,沉默ADAMTS19组Ishikawa细胞的增殖、迁移和侵袭能力明显增强,差异具有统计学意义(增殖:P<0.001,迁移:P<0.05,侵袭:P<0.001)。沉默ADAMTS19组中p-STAT3蛋白的表达水平明显增强(P<0.05)。结论ADAMTS19在子宫内膜癌组织中呈低表达,且与子宫内膜恶性临床特征密切相关,可能是通过促进磷酸化STAT3的表达促进肿瘤细胞增殖、迁移和侵袭能力。ADAMTS19有望成为子宫内膜癌潜在的分子靶标。
基金supported by the National Natural Science Foundation of China(No.82003561).
文摘Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.
基金supported by grants from the National Natural Science Foundation of China (81874175, 81902377, 81802317, and 81702844)。
文摘Background: ADAMTS(a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma(PDAC). Methods: We used several databases to analyze the ADAMTS family and then screen out the hub genes. The expression of ADAMTS12 in 106 pairs of PDAC tumors and adjacent normal tissues was examined by immunohistochemistry, and its correlations with clinical parameters were further analyzed. The impacts of ADAMTS12 on the migration of PDAC cells were predicted by gene set enrichment analysis and confirmed by transwell assays. The potential impacts of ADAMTS12 on the epithelial-mesenchymal transition(EMT) were identified by database analysis and experimental proof of real-time quantitative polymerase chain reaction(q PCR) and Western blotting. Results: Our study found that ADAMTS12 was a crucial gene in PDAC, and it was highly expressed in tumor tissues when compared to that in the adjacent tissues. ADATMS12 had predictive value of a poor prognosis for PDAC. The elevation of ADAMTS12 was parallel to the progression of PDAC. Inhibition of ADAMTS12 suppressed the migration of PDAC cells and interfered with the process of EMT. Conclusions: ADAMTS12 is a crucial member of ADAMTSs in PDAC and a predictor of poor prognosis. Additionally, based on its impacts on migration and metastasis in PDAC and the relationship with EMT, ADAMTS12 plays a role of an oncogene in PDAC and may be a promising target for treatment.
基金Supported by The Cadre Health Research Program of the Sichuan Province (No.2023-119)Sichuan Science and Technology Program (No.2021YFS0213)。
文摘AIM: To explore the phenotype and genotype of WeillMarchesani syndrome(WMS) in a Chinese family and review related literature.METHODS: Three WMS patients and other unaffected individuals in this family with a history of consanguineous marriage were included in this study. Medical history, comprehensive ophthalmic examinations, and systemic evaluation, as well as whole exome and Sanger sequencing of specific genomic regions, were performed. RESULTS: The three affected siblings presented with short stature, brachydactyly and ocular disorders, including very shallow anterior chamber, high myopia, microspherophakia lens subluxation with stretched zonules and glaucoma. Genetic analysis verified a homozygous missense mutation(c.2983C>T: p. Arg995Trp) in ADAMTS17,which was correlated with the diseases in this family, indicating an autosomal recessive inherited manner of WMS. This review aims to summarize the mutation sites of WMS genes, so as to prevent the disease and better guide clinical diagnosis and treatment.CONCLUSION: A novel homozygous missense variant of ADAMTS17 is identified in a WMS family with a history of consanguineous marriage. Our study expands the range of mutations associated with WMS and deepens our understanding of pathology in disease associated with ADAMTS17 variants.
基金The Wu Jieping Medical Foundation Clinical Research Special Grant Fund in China,No.320.6750.2022-15-9.
文摘BACKGROUND Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels.Congenital lymphangiectasia can affect various organ systems;however,it frequently occurs in the lungs accompanied with unexplained pleural effusion.Further,it might not be diagnosed during prenatal examination owing to the absence of pronounced abnormalities.However,after birth the newborn rapidly develops respiratory distress that quickly deteriorates.Genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of this disease.We report a rare case of heterozygous mutation of ADAMTS3 and FLT4 genes,which have not been reported previously.CASE SUMMARY We analysed the case of a neonate who had presented with only pleural effusion at a late gestational age and eventually died due to its inability to establish spontaneous breathing after birth.An autopsy revealed lymphangiectasia of the organ systems.Further,whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes,ADAMTS3 and FLT4,and Sanger verification revealed similar lesions in the mother with no symptoms.CONCLUSION Considering the presented case,obstetricians should observe unexplained foetal pleural effusion,and perform pathology analysis and whole exome sequencing for a conclusive diagnosis and prompt treatment.
