Summary: To determine the (tttta) n repeat polymorphisms at the promoter region of CYP11α gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study w...Summary: To determine the (tttta) n repeat polymorphisms at the promoter region of CYP11α gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11α (tttta) n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP11α (tttta) n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0.16, 0.33, 0.38, and 0.13 respectively in PCOS patients, as compared with 0.20, 0.34, 0.35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11α gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta) n of gene CYP11α exists in Chinese women and the polymorphism of CYP11α gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.展开更多
BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare disease with clinical manifestations of pigmented spots on the lips,mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors.The c...BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare disease with clinical manifestations of pigmented spots on the lips,mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors.The clinical heterogeneity of PJS is obvious,and the relationship between clinical phenotype and genotype is still unclear.AIM To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of PJS.METHODS Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center(former Air Force General Hospital)PLA between 2008 and 2017.Their hamartoma polyp tissues were used for APC,AXIN2,BMPR1A,EPCAM,MLH1,MLH3,MSH2,MSH6,MUTYH,PMS1,PMS2,PTEN,SMAD4,and LKB1/STK11 gene sequencing using next-generation sequencing technology.The correlations between the sequencing results and clinical pathological data of PJS were analyzed.RESULTS Fourteen types of LKB1/STK11 mutations were detected in 16 cases(80.0%),of which 8 new mutations were found(3 types of frameshift deletion mutations:c.243delG,c.363_364delGA,and c.722delC;2 types of frameshift insertions:c.144_145insGCAAG,and c.454_455insC;3 types of splice site mutations:c.464+1G>T,c.464+1G>A,and c.598-1G>A);9 cases(45.0%)were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/STK11.Of these,MSH2:c.792+1G>A,MSH6:c.3689C>G,c.4001+13C>CTTAC,PMS1:c.46C>t,and c.922G>A were new mutations.CONCLUSION The genetic mutations in hamartoma polyp tissue of PJS are complex and diverse.Moreover,other gene mutations in PJS hamartoma polyp tissue were observed,with the exception of LKB1/STK11 gene,especially the DNA mismatch repair gene(MMR).Colorectal hamartoma polyps with LKB1/STK11 mutations were larger in diameter than those with other gene mutations.展开更多
PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first ident...PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.展开更多
identify aldosterone synthase gene CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone Methods 160 Wistar rats weighing about 250?g were divided into 4 grou...identify aldosterone synthase gene CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone Methods 160 Wistar rats weighing about 250?g were divided into 4 groups In the model group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week In the antisterone group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Antisterone equivalent to 20?mg·kg 1 ·d 1 was given intragastrically (ig) In the malotilate group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Malotilate equivalent to 50?mg·kg 1 ·d 1 was given ig In the control group (n=40), the rats were injected with olive oil only After 2,4,6,8 and 10 weeks, animals were sacrificed, and morphological examination was carried out The area of collagen was examined with an Image Analyse System Expression of the aldosterone synthase gene, CYP11B2 mRNA, in fibrotic and normal liver was detected by means of reverse transcriptase polymerase chain reaction (RT PCR) and in situ hybridization Results In situ hybridization and RT PCR showed that the expression of CYP11B2 mRNA, which localized in the endoplasm of hepatic stellate cells (HSCs), was up regulated when fibrogenesis occurred Histological observation indicated that the grade of fibrosis and the area of collagen in the antisterone group were less than those in model group before 6 weeks ( P <0 05) There was no significant difference between the antisterone and malotilate groups ( P >0 05) After that, however, the grade of fibrosis and the area of collagen in the antisterone group were higher than those in the malotilate group ( P <0 05) There was no significant difference between the antisterone and model groups ( P >0 05) Conclusions The expression of CYP11B2 mRNA is up regulated in fibrotic liver Antisterone can have a partial fibrogenesis inhibiting effect in the early stages展开更多
A male infant with clinical features of Noonan syndrome and rapidly progressiv e hypertrophic cardiomyopathy is reported. He manifested severe heart failure an d failure to thrive. Administration of propranolol and ci...A male infant with clinical features of Noonan syndrome and rapidly progressiv e hypertrophic cardiomyopathy is reported. He manifested severe heart failure an d failure to thrive. Administration of propranolol and cibenzoline improved vent ricular outflow tract obstruction, leading to catch-up growth. Genetic analysis of the patient revealed a novel missense mutation in the PTPN11 gene. Conclusio n:This is the first description of a patient with a Gln510Glu mutation in the pr otein-tyrosine phosphatase, non-receptor type 11 gene. This specific mutation may be associated with a rapidly progressive hypertrophic cardiomyopathy.展开更多
基金This project was supported by a grant of Henan Provincial Bureau of Science and Technology (No. 0424410097).
文摘Summary: To determine the (tttta) n repeat polymorphisms at the promoter region of CYP11α gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11α (tttta) n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP11α (tttta) n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0.16, 0.33, 0.38, and 0.13 respectively in PCOS patients, as compared with 0.20, 0.34, 0.35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11α gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta) n of gene CYP11α exists in Chinese women and the polymorphism of CYP11α gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.
基金Supported by Major Projects of the Chinese PLA"Thirteenth Five-Year Plan"Logistics Research Subject,No.AKJ15J003No.AKJ15J001+1 种基金Incubation Project of Military Medical Science and Technology Youth Cultivation Program,No.17QNP023Beijing Capital Medical Development Research Fund,No.Shoufa2020-2-5122.
文摘BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare disease with clinical manifestations of pigmented spots on the lips,mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors.The clinical heterogeneity of PJS is obvious,and the relationship between clinical phenotype and genotype is still unclear.AIM To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of PJS.METHODS Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center(former Air Force General Hospital)PLA between 2008 and 2017.Their hamartoma polyp tissues were used for APC,AXIN2,BMPR1A,EPCAM,MLH1,MLH3,MSH2,MSH6,MUTYH,PMS1,PMS2,PTEN,SMAD4,and LKB1/STK11 gene sequencing using next-generation sequencing technology.The correlations between the sequencing results and clinical pathological data of PJS were analyzed.RESULTS Fourteen types of LKB1/STK11 mutations were detected in 16 cases(80.0%),of which 8 new mutations were found(3 types of frameshift deletion mutations:c.243delG,c.363_364delGA,and c.722delC;2 types of frameshift insertions:c.144_145insGCAAG,and c.454_455insC;3 types of splice site mutations:c.464+1G>T,c.464+1G>A,and c.598-1G>A);9 cases(45.0%)were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/STK11.Of these,MSH2:c.792+1G>A,MSH6:c.3689C>G,c.4001+13C>CTTAC,PMS1:c.46C>t,and c.922G>A were new mutations.CONCLUSION The genetic mutations in hamartoma polyp tissue of PJS are complex and diverse.Moreover,other gene mutations in PJS hamartoma polyp tissue were observed,with the exception of LKB1/STK11 gene,especially the DNA mismatch repair gene(MMR).Colorectal hamartoma polyps with LKB1/STK11 mutations were larger in diameter than those with other gene mutations.
基金funded by NIH grants R01DK075916 and R01HL096125supported by Chinese National Key Project(2012ZX10002-009,011,013)+2 种基金National Natural Science Foundation of China(Grant Nos.30921006,30900770)Key Basic Science Foundation of Shanghai(10JC1418500)Project of the State Key Laboratory of Shanghai Jiaotong University(91-10-02).
文摘PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.
基金theNationalNaturalScienceFoundationofChina (No 39870 331)
文摘identify aldosterone synthase gene CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone Methods 160 Wistar rats weighing about 250?g were divided into 4 groups In the model group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week In the antisterone group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Antisterone equivalent to 20?mg·kg 1 ·d 1 was given intragastrically (ig) In the malotilate group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Malotilate equivalent to 50?mg·kg 1 ·d 1 was given ig In the control group (n=40), the rats were injected with olive oil only After 2,4,6,8 and 10 weeks, animals were sacrificed, and morphological examination was carried out The area of collagen was examined with an Image Analyse System Expression of the aldosterone synthase gene, CYP11B2 mRNA, in fibrotic and normal liver was detected by means of reverse transcriptase polymerase chain reaction (RT PCR) and in situ hybridization Results In situ hybridization and RT PCR showed that the expression of CYP11B2 mRNA, which localized in the endoplasm of hepatic stellate cells (HSCs), was up regulated when fibrogenesis occurred Histological observation indicated that the grade of fibrosis and the area of collagen in the antisterone group were less than those in model group before 6 weeks ( P <0 05) There was no significant difference between the antisterone and malotilate groups ( P >0 05) After that, however, the grade of fibrosis and the area of collagen in the antisterone group were higher than those in the malotilate group ( P <0 05) There was no significant difference between the antisterone and model groups ( P >0 05) Conclusions The expression of CYP11B2 mRNA is up regulated in fibrotic liver Antisterone can have a partial fibrogenesis inhibiting effect in the early stages
文摘A male infant with clinical features of Noonan syndrome and rapidly progressiv e hypertrophic cardiomyopathy is reported. He manifested severe heart failure an d failure to thrive. Administration of propranolol and cibenzoline improved vent ricular outflow tract obstruction, leading to catch-up growth. Genetic analysis of the patient revealed a novel missense mutation in the PTPN11 gene. Conclusio n:This is the first description of a patient with a Gln510Glu mutation in the pr otein-tyrosine phosphatase, non-receptor type 11 gene. This specific mutation may be associated with a rapidly progressive hypertrophic cardiomyopathy.
