The disorder, Maturity Onset of Diabetes of the young (MODY) is a monogenic form of Non-Insulin dependent Diabetes Mellitus (NIDDM), characterized by autosomal dominant mode of inheritance and onset is usually before ...The disorder, Maturity Onset of Diabetes of the young (MODY) is a monogenic form of Non-Insulin dependent Diabetes Mellitus (NIDDM), characterized by autosomal dominant mode of inheritance and onset is usually before 25 years of age. Clinical studies of subjects with the different forms of MODY indicate that each is associated with a different defect in the normal pattern of glucose stimulated insulin secretion. MODY can result from mutations in any one of the six different genes, one of which encodes the glycolytic enzyme Glucokinase, associated with MO-DY2 and the other five encode transcription factors HNF4-alpha associated with MODY 1, HNF1-alpha associated with MODY 3, IPF with MODY 4, HNF1-Beta with MODY 5 and NeuroD1 with MO-DY6. Studies related to mutations in the MODY genes have led to a better understanding of the genetic causes of the Beta cell dysfunction as genetic factors plays a great role in this disorder. Objective: To investigate the mutation pattern in the different transcription factor genes with special reference to HNF1-alpha which are highly penetrant with 63% mutation carriers manifesting clinical diabetes by the age of 25 years. Hence study of mutation pattern in this gene is essential in our population i.e. Eastern Indian population. Our study is focused on HNF1-alpha related to MODY 3, which is the most common one. Methods: In our study enzyme amplification (PCR) of the 10 target exons of the said gene with simultaneous mutation detection in them by PCR-SSCP (Polymerase chain reaction-single strand conformational polymorphism) reaction analysis method was attempted by screening of exon 1 - 10 with respect to normal healthy controls without Diabetes Mellitus. The nature of the specific mutations was also determined by sequencing. Result: It was observed that maximum number of variations exist in exon 5 of HNF1-alpha gene which may be referred to as “Mutational Hotspot” in our Eastern Indian population. Conclusions: Since maximum number of variations exists in exon 5 of the said gene, hence one can initially go for exon5 followed by other exons, while screening for pathogenic MODY 3 mutations in the responsible gene by PCR-SSCP method.展开更多
目的探讨血清壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)、甲胎蛋白(alpha fetoprotein,AFP)和γ-谷氨酰转移酶(γ-glutamyl transferase,GGT)检测在乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝癌诊断中的临床应用价值...目的探讨血清壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)、甲胎蛋白(alpha fetoprotein,AFP)和γ-谷氨酰转移酶(γ-glutamyl transferase,GGT)检测在乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝癌诊断中的临床应用价值。方法选取2021年7月—2023年7月在玉林市第一人民医院就诊HBV病毒感染相关的50例肝癌患者,50例肝硬化患者,50例慢性乙型肝炎患者以及50名同期健康体检者作为研究对象。比较4组研究对象血清中CHI3L1、AFP、GGT、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)等水平的差异,用受试者工作特征(receiver operating characteristic curve,ROC)曲线评估各指标在肝癌中的诊断价值。结果肝炎组、肝硬化组、肝癌组的CHI3L1、AST、ALT水平均高于对照组,肝癌组AFP、GGT水平高于对照组,差异有统计学意义(P<0.05)。与肝炎组比较,肝硬化组及肝癌组的CHI3L1、AFP、GGT、AST、ALT水平均升高,差异有统计学意义(P<0.05)。与肝硬化组比较,肝癌组的CHI3L1、AFP、GGT、AST水平均升高,差异有统计学意义(P<0.05)。ROC曲线分析显示,CHI3L1、AFP、GGT联合时的曲线下面积(area under the curve,AUC)最大(AUC=0.936)。Spearman相关分析结果显示,CHI3L1与AST呈正相关(r=0.414,P=0.003),AFP与GGT呈正相关(r=0.437,P=0.002),AFP与AST呈正相关(r=0.504,P<0.001),GGT与AST呈正相关(r=0.759,P<0.001),GGT与ALT呈正相关(r=0.636,P<0.001)。结论CHI3L1、AFP及GGT联合检测可提高肝癌的诊断价值,对临床肝癌患者诊疗有重要作用。展开更多
目的:探讨微环境中Ⅸ型胶原α1(collagen type IX alpha 1 chain,COL9A1)在结直肠腺癌中的表达及其与肿瘤进展的相关性和临床意义。方法:收集2012年1月至2021年1月手术切除的结直肠癌标本408例,采用免疫组织化学检测结直肠腺癌肿瘤组织...目的:探讨微环境中Ⅸ型胶原α1(collagen type IX alpha 1 chain,COL9A1)在结直肠腺癌中的表达及其与肿瘤进展的相关性和临床意义。方法:收集2012年1月至2021年1月手术切除的结直肠癌标本408例,采用免疫组织化学检测结直肠腺癌肿瘤组织及癌旁正常组织中COL9A1表达,同时检测肿瘤组织中肿瘤蛋白53(tumor protein 53,P53)和错配修复(mismatch repair,MMR)蛋白MLH1、MSH6和PMS2的表达,统计分析COL9A1的表达与各临床病理特征参数的关系,以及与P53突变和MMR状态的相关性,并分析COL9A1阳性表达患者的预后情况。结果:COL9A1在结直肠腺癌肿瘤组织中表达显著低于癌旁正常组织(P<0.001);COL9A1的表达与肿瘤浸润深度、临床分期和肠系膜淋巴结转移有关(χ^(2)=16.943、89.031和84.814;均P<0.001),而与P53突变和MMR状态无关(χ^(2)=0.677、1.260,均P>0.05);Log-rank检验显示COL9A1阴性表达患者的无进展生存期(progression free survival,PFS)和总体生存期(overall survival,OS)显著低于COL9A1阳性表达患者(分别P<0.001,P=0.040)。结论:结直肠腺癌中COL9A1蛋白的表达缺失与肿瘤浸润及转移密切相关,并提示不良预后,这可为结直肠癌预后评估、药物筛选等提供可能的分子标志物和治疗策略。展开更多
文摘The disorder, Maturity Onset of Diabetes of the young (MODY) is a monogenic form of Non-Insulin dependent Diabetes Mellitus (NIDDM), characterized by autosomal dominant mode of inheritance and onset is usually before 25 years of age. Clinical studies of subjects with the different forms of MODY indicate that each is associated with a different defect in the normal pattern of glucose stimulated insulin secretion. MODY can result from mutations in any one of the six different genes, one of which encodes the glycolytic enzyme Glucokinase, associated with MO-DY2 and the other five encode transcription factors HNF4-alpha associated with MODY 1, HNF1-alpha associated with MODY 3, IPF with MODY 4, HNF1-Beta with MODY 5 and NeuroD1 with MO-DY6. Studies related to mutations in the MODY genes have led to a better understanding of the genetic causes of the Beta cell dysfunction as genetic factors plays a great role in this disorder. Objective: To investigate the mutation pattern in the different transcription factor genes with special reference to HNF1-alpha which are highly penetrant with 63% mutation carriers manifesting clinical diabetes by the age of 25 years. Hence study of mutation pattern in this gene is essential in our population i.e. Eastern Indian population. Our study is focused on HNF1-alpha related to MODY 3, which is the most common one. Methods: In our study enzyme amplification (PCR) of the 10 target exons of the said gene with simultaneous mutation detection in them by PCR-SSCP (Polymerase chain reaction-single strand conformational polymorphism) reaction analysis method was attempted by screening of exon 1 - 10 with respect to normal healthy controls without Diabetes Mellitus. The nature of the specific mutations was also determined by sequencing. Result: It was observed that maximum number of variations exist in exon 5 of HNF1-alpha gene which may be referred to as “Mutational Hotspot” in our Eastern Indian population. Conclusions: Since maximum number of variations exists in exon 5 of the said gene, hence one can initially go for exon5 followed by other exons, while screening for pathogenic MODY 3 mutations in the responsible gene by PCR-SSCP method.
文摘目的探讨血清壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)、甲胎蛋白(alpha fetoprotein,AFP)和γ-谷氨酰转移酶(γ-glutamyl transferase,GGT)检测在乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝癌诊断中的临床应用价值。方法选取2021年7月—2023年7月在玉林市第一人民医院就诊HBV病毒感染相关的50例肝癌患者,50例肝硬化患者,50例慢性乙型肝炎患者以及50名同期健康体检者作为研究对象。比较4组研究对象血清中CHI3L1、AFP、GGT、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)等水平的差异,用受试者工作特征(receiver operating characteristic curve,ROC)曲线评估各指标在肝癌中的诊断价值。结果肝炎组、肝硬化组、肝癌组的CHI3L1、AST、ALT水平均高于对照组,肝癌组AFP、GGT水平高于对照组,差异有统计学意义(P<0.05)。与肝炎组比较,肝硬化组及肝癌组的CHI3L1、AFP、GGT、AST、ALT水平均升高,差异有统计学意义(P<0.05)。与肝硬化组比较,肝癌组的CHI3L1、AFP、GGT、AST水平均升高,差异有统计学意义(P<0.05)。ROC曲线分析显示,CHI3L1、AFP、GGT联合时的曲线下面积(area under the curve,AUC)最大(AUC=0.936)。Spearman相关分析结果显示,CHI3L1与AST呈正相关(r=0.414,P=0.003),AFP与GGT呈正相关(r=0.437,P=0.002),AFP与AST呈正相关(r=0.504,P<0.001),GGT与AST呈正相关(r=0.759,P<0.001),GGT与ALT呈正相关(r=0.636,P<0.001)。结论CHI3L1、AFP及GGT联合检测可提高肝癌的诊断价值,对临床肝癌患者诊疗有重要作用。
文摘目的:探讨微环境中Ⅸ型胶原α1(collagen type IX alpha 1 chain,COL9A1)在结直肠腺癌中的表达及其与肿瘤进展的相关性和临床意义。方法:收集2012年1月至2021年1月手术切除的结直肠癌标本408例,采用免疫组织化学检测结直肠腺癌肿瘤组织及癌旁正常组织中COL9A1表达,同时检测肿瘤组织中肿瘤蛋白53(tumor protein 53,P53)和错配修复(mismatch repair,MMR)蛋白MLH1、MSH6和PMS2的表达,统计分析COL9A1的表达与各临床病理特征参数的关系,以及与P53突变和MMR状态的相关性,并分析COL9A1阳性表达患者的预后情况。结果:COL9A1在结直肠腺癌肿瘤组织中表达显著低于癌旁正常组织(P<0.001);COL9A1的表达与肿瘤浸润深度、临床分期和肠系膜淋巴结转移有关(χ^(2)=16.943、89.031和84.814;均P<0.001),而与P53突变和MMR状态无关(χ^(2)=0.677、1.260,均P>0.05);Log-rank检验显示COL9A1阴性表达患者的无进展生存期(progression free survival,PFS)和总体生存期(overall survival,OS)显著低于COL9A1阳性表达患者(分别P<0.001,P=0.040)。结论:结直肠腺癌中COL9A1蛋白的表达缺失与肿瘤浸润及转移密切相关,并提示不良预后,这可为结直肠癌预后评估、药物筛选等提供可能的分子标志物和治疗策略。
