目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显...目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子14和23,再对PCR产物进行DNA测序分析。结果所有ICP患者及对照组外周血DNA经PCR均扩增出目的片段,外显子14和23均未发现有突变。结论云南临沧佤族、傣族ICP的发生可能与MDR3基因外显子14和23突变无关。展开更多
目的:建立和验证人孕烷X受体(human pregnant X receptor,hPXR)介导的CYP3A4、MDR1药物诱导剂的体外筛选体系,考察豆腐果苷对hPXR介导的CYP3A4、MDR1的转录调节作用。方法:利用构建的双荧光素酶报告基因系统,将表达载体和报告载体共转染...目的:建立和验证人孕烷X受体(human pregnant X receptor,hPXR)介导的CYP3A4、MDR1药物诱导剂的体外筛选体系,考察豆腐果苷对hPXR介导的CYP3A4、MDR1的转录调节作用。方法:利用构建的双荧光素酶报告基因系统,将表达载体和报告载体共转染HepG2细胞,以10μmol/L利福平为阳性对照,用不同浓度(0.004、0.04、0.4μmol/L)豆腐果苷处理48h后裂解细胞进行双荧光素酶活性检测。结果:不同浓度的豆腐果苷均不能通过激活hPXR来介导CYP3A4和MDR1表达上调,各浓度处理组的双荧光素酶比活性值与DMSO溶媒组差异无统计学意义(P>0.05)。结论:成功构建了hPXR介导的CYP3A4和MDR1药物诱导剂的体外筛选体系,并发现豆腐果苷不能通过激活hPXR介导CYP3A4和MDR1的表达上调。展开更多
BACKGROUND Mutations that occur in the ABCB4 gene,which encodes multidrug-resistant protein 3,underlie the occurrence of progressive familial intrahepatic cholestasis type 3(PFIC3).Clinical signs of intrahepatic chole...BACKGROUND Mutations that occur in the ABCB4 gene,which encodes multidrug-resistant protein 3,underlie the occurrence of progressive familial intrahepatic cholestasis type 3(PFIC3).Clinical signs of intrahepatic cholestasis due to gene mutations typically first appear during infancy or childhood.Reports of PFIC3 occurring in adults are rare.CASE SUMMARY This is a case study of a 32-year-old infertile female Chinese patient with a 15-year history of recurrent abnormal liver function.Her primary clinical signs were elevated levels of alkaline phosphatase andγ-glutamyl transpeptidase.Other possible reasons for liver dysfunction were eliminated in this patient,resulting in a diagnosis of PFIC3.The diagnosis was confirmed using gene detection and histological analyses.Assessments using genetic sequencing analysis indicated the presence of two novel heterozygous mutations in the ABCB4 gene,namely,a 2950C>T;p.A984V mutation(exon 24)and a 667A>G;p.I223V mutation(exon 7).After receiving ursodeoxycholic acid(UDCA)treatment,the patient's liver function indices improved,and she successfully became pregnant by in vitro fertilization.However,the patient developed intrahepatic cholestasis of pregnancy in the first trimester.Fortunately,treatment with UDCA was safe and effective.CONCLUSION These novel ABCB4 heterozygous mutations have a variety of clinical phenotypes.Continued follow-up is essential for a comprehensive understanding of PFIC3.展开更多
BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused ...BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.展开更多
A novel class of molecules with structure N-（3-arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides （20- 29） were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design so...A novel class of molecules with structure N-（3-arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides （20- 29） were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P-glycoprotein （P-gp） by standard Hoechst 33342 assay method. Based on the pIC50 values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard.展开更多
目的:探索妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子6和9突变与ICP发病的关系。方法:从云南省临沧地区各少数民族自治县29例ICP患者及32例正常孕妇及患者家属组的外周血中提取DNA,聚合酶链反...目的:探索妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子6和9突变与ICP发病的关系。方法:从云南省临沧地区各少数民族自治县29例ICP患者及32例正常孕妇及患者家属组的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子6和9,PCR产物进行DNA测序分析。结果:所有ICP患者及对照组PCR均扩增出目的片段,且外显子6存在多态性位点C158T,外显子9存在突变位点G581A,但两组的基因频率无明显差异。结论:云南省临沧少数民族地区ICP的发生可能与MDR3外显子6和9的突变无关。展开更多
文摘目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子14和23,再对PCR产物进行DNA测序分析。结果所有ICP患者及对照组外周血DNA经PCR均扩增出目的片段,外显子14和23均未发现有突变。结论云南临沧佤族、傣族ICP的发生可能与MDR3基因外显子14和23突变无关。
文摘目的:建立和验证人孕烷X受体(human pregnant X receptor,hPXR)介导的CYP3A4、MDR1药物诱导剂的体外筛选体系,考察豆腐果苷对hPXR介导的CYP3A4、MDR1的转录调节作用。方法:利用构建的双荧光素酶报告基因系统,将表达载体和报告载体共转染HepG2细胞,以10μmol/L利福平为阳性对照,用不同浓度(0.004、0.04、0.4μmol/L)豆腐果苷处理48h后裂解细胞进行双荧光素酶活性检测。结果:不同浓度的豆腐果苷均不能通过激活hPXR来介导CYP3A4和MDR1表达上调,各浓度处理组的双荧光素酶比活性值与DMSO溶媒组差异无统计学意义(P>0.05)。结论:成功构建了hPXR介导的CYP3A4和MDR1药物诱导剂的体外筛选体系,并发现豆腐果苷不能通过激活hPXR介导CYP3A4和MDR1的表达上调。
基金Supported by Natural Science Foundation of Gansu Province,No.21JR7RA410.
文摘BACKGROUND Mutations that occur in the ABCB4 gene,which encodes multidrug-resistant protein 3,underlie the occurrence of progressive familial intrahepatic cholestasis type 3(PFIC3).Clinical signs of intrahepatic cholestasis due to gene mutations typically first appear during infancy or childhood.Reports of PFIC3 occurring in adults are rare.CASE SUMMARY This is a case study of a 32-year-old infertile female Chinese patient with a 15-year history of recurrent abnormal liver function.Her primary clinical signs were elevated levels of alkaline phosphatase andγ-glutamyl transpeptidase.Other possible reasons for liver dysfunction were eliminated in this patient,resulting in a diagnosis of PFIC3.The diagnosis was confirmed using gene detection and histological analyses.Assessments using genetic sequencing analysis indicated the presence of two novel heterozygous mutations in the ABCB4 gene,namely,a 2950C>T;p.A984V mutation(exon 24)and a 667A>G;p.I223V mutation(exon 7).After receiving ursodeoxycholic acid(UDCA)treatment,the patient's liver function indices improved,and she successfully became pregnant by in vitro fertilization.However,the patient developed intrahepatic cholestasis of pregnancy in the first trimester.Fortunately,treatment with UDCA was safe and effective.CONCLUSION These novel ABCB4 heterozygous mutations have a variety of clinical phenotypes.Continued follow-up is essential for a comprehensive understanding of PFIC3.
基金Supported by The Department of Science and Technology of Guizhou Province,No.[2020]1Y299National Natural Science Foundation of China,No.82060123+2 种基金National Health Commission of Guizhou Province,No.gzwjk2019-1-082Doctor Start Fund of Affiliated Hospital of Guizhou Medical University,No.gyfybsky-2021-28National Natural Cultivation Fund of Affiliated Hospital of Guizhou Medical University,No.Ⅰ-2020-12.
文摘BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.
文摘A novel class of molecules with structure N-（3-arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides （20- 29） were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P-glycoprotein （P-gp） by standard Hoechst 33342 assay method. Based on the pIC50 values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard.
文摘目的:探索妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子6和9突变与ICP发病的关系。方法:从云南省临沧地区各少数民族自治县29例ICP患者及32例正常孕妇及患者家属组的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子6和9,PCR产物进行DNA测序分析。结果:所有ICP患者及对照组PCR均扩增出目的片段,且外显子6存在多态性位点C158T,外显子9存在突变位点G581A,但两组的基因频率无明显差异。结论:云南省临沧少数民族地区ICP的发生可能与MDR3外显子6和9的突变无关。
