Hepatocyte nuclear factor 1-β(HNF1B)defects cause renal cysts and diabetes syndrome(RCAD),or HNF1B-maturity-onset diabetes of the young.However,the hepatic phenotype of HNF1B variants is not well studied.We present a...Hepatocyte nuclear factor 1-β(HNF1B)defects cause renal cysts and diabetes syndrome(RCAD),or HNF1B-maturity-onset diabetes of the young.However,the hepatic phenotype of HNF1B variants is not well studied.We present a female neonate born small for her gestational age[birth weight 2360 g;-2.02standard deviations(SD)and birth length 45 cm;-2.40 SD at the 38th gestational week].She developed neonatal cholestasis due to biliary atresia and required surgical intervention(portoenterostomy)when 32-d old.Following the operation,icterus resolved,but laboratory signs of liver dysfunction persisted.She had hyperechogenic kidneys prenatally with bilateral renal cysts and pancreatic hypoplasia postnatally that led to the diagnosis of an HNF1B deletion.This represents the most severe hepatic phenotype of an HNF1B variant recognized thus far.A review of 12 published cases with hepatic phenotypes of HNF1B defects allowed us to distinguish three severity levels,ranging from neonatal cholestasis through adult-onset cholestasis to noncholestatic liver impairment,all of these are associated with congenital renal cysts and mostly with diabetes later in life.We conclude that to detect HNF1B variants,neonates with cholestasis should be checked for the presence of renal cysts,with special focus on those who are born small for their gestational age.Additionally,patients with diabetes and renal cysts at any age who develop cholestasis and/or exocrine pancreatic insufficiency should be tested for HNF1B variants as the true etiological factor of all disease components.Further observations are needed to confirm the potential reversibility of cholestasis in infancy in HNF1B mutation/deletion carriers.展开更多
玻璃体切除术(pars plana vitrectomy,PPV)为增殖性糖尿病视网膜病变(proliferative diabeticretinopathy,PDR)常用治疗手段,但手术难度大、出血量多,难以有效控制,会延长手术时间、增加手术失败风险。采取有效措施优化治疗,降低手术风...玻璃体切除术(pars plana vitrectomy,PPV)为增殖性糖尿病视网膜病变(proliferative diabeticretinopathy,PDR)常用治疗手段,但手术难度大、出血量多,难以有效控制,会延长手术时间、增加手术失败风险。采取有效措施优化治疗,降低手术风险是近年来的研究热点。展开更多
The ‘‘omics sciences’’ (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns o...The ‘‘omics sciences’’ (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns of genes, miRNA, proteins, and metabolites. This study aimed, through bioinformatics and systems biology, to decipher the cytokinome profile in the evolution of inflammatory processes leading to cancer. The cytokinome was defined as the totality of cytokines and their interactions in and around biological cells. The system biology approach would provide a better understanding of the complex interaction network of cytokines, especially in cancer patients. Acquired knowledge would enable health providers with tools to evaluate disease onset through progression as well as identifying innovative therapeutic strategies. Understanding the role each cytokine plays in the metabolic network is of great importance. This paper reviews our group’s ‘‘omics’’ work. In particular, it addresses the role cytokines play in liver disease in six different scenarios. The first is the role the cytokines play in chronic inflammatory diseases and cancers. The second is the significance of the cytokinome profile. The third is the role of liver cirrhosis as an inflammatory disease. The fourth is the comparison of cytokine levels evaluated in patients with chronic hepatitis C virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of type 2 diabetes. And lastly, we present a comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of hepatocellular carcinoma.展开更多
A highly-fractionated garnet-bearing muscovite granite represents the marginal granitic facies of the Abu-Diab multiphase pluton in the Central Eastern Desert of Egypt. New electron microprobe analyses(EMPA) and laser...A highly-fractionated garnet-bearing muscovite granite represents the marginal granitic facies of the Abu-Diab multiphase pluton in the Central Eastern Desert of Egypt. New electron microprobe analyses(EMPA) and laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS) data from garnets are reported, in order to constrain their origin and genesis. Garnet in the Abu-Diab host granite is euhedral to subhedral, generally homogeneous and, in rare cases, it shows weak zonation. The garnet contains appreciable amounts of MnO and FeO, with lesser amounts of MgO and CaO, yielding an end-member formula of Sps61–72Alm25–35Prp1–4Adr0–1. Moreover, it is depleted in large ion lithophile elements(LILE) with lower values of Ba, Nb and Sr relative to the primitive mantle. Additionally, it contains high concentrations of HREE and Y and their REE pattern shows strong negative Eu anomalies. The garnet was crystallized under relatively low temperature(646°C–591°C) and pressure(< 3 kbar) conditions. The textural and chemical features indicate that the garnet is magmatic in origin and is chemically similar to that from highly-fractionated A-type granite. It was probably formed at the expense of biotite in a highly-evolved MnO-rich magma and/or by hydroxyl complexing of Mn during the ascending fluid phases.展开更多
糖尿病（Diabetes）
Pharmacist：Hello!What can I do for you？
药师：您好,请问您需要什么帮助？
Client：I want to ask you about general in-structions on how to take medication for diab etes.
顾客：我想咨询一下有关糖...糖尿病（Diabetes）
Pharmacist：Hello!What can I do for you？
药师：您好,请问您需要什么帮助？
Client：I want to ask you about general in-structions on how to take medication for diab etes.
顾客：我想咨询一下有关糖尿病的用药常识。展开更多
Background:Overexpression of inducible nitric oxide synthase(iNOS)has been reported in diabetic retinopathy(DR).The kinin B1 receptor(B1R)is also overexpressed in DR,and can stimulate iNOS via Gαi/ERK/MAPK pathway.We...Background:Overexpression of inducible nitric oxide synthase(iNOS)has been reported in diabetic retinopathy(DR).The kinin B1 receptor(B1R)is also overexpressed in DR,and can stimulate iNOS via Gαi/ERK/MAPK pathway.We previously showed that the topical administration of a B1R antagonist,LF22-0542,significantly reduces leukocyte infiltration,increased vascular permeability and overexpression of several inflammatory mediators,including iNOS in DR.Thus,the aim of this study was to determine whether the pro-inflammatory effects of B1R are attributed to oxidative stress caused by the activation of iNOS pathway in order to identify new therapeutic targets for the treatment of DR.iNOS and B1R being absent in the normal retina,their inhibition is unlikely to result in undesirable side effects.The approach will be no invasive by eye application of drops.Methods:Diabetes was induced in male Wistar rats(200-230 g)by a single intraperitoneal injection of streptozotocin(STZ,65 mg/kg b.w).One week later,rats were randomly divided into four groups(N=5)and treated for one week as follows:Gr 1:control rats treated with the selective iNOS inhibitor(1,400 W,0.06μM twice a day by eye-drops×7 days),Gr 2,STZ-diabetic rats treated with 1,400 W,Gr 3:control rats received a selective B1R agonist[Sar(D-Phe8)-des-Arg9-BK,100μg twice a week]by intravitreal injections(itrv)and treated with 1,400 W,Gr 4:STZ-diabetic rats+B1R agonist+1,400 W.At the end of treatment and two weeks post-STZ,three series of experiments were carried out to measure vascular permeability(by Evans blue dye method)and the expression of vasoactive and inflammatory mediators,including iNOS,VEGF-A,VEGF-R2,IL-1β,Cox-2,TNF-α,bradykinin 1 and 2 receptors and carboxypeptidase M/kininase 1(by Western Blotting and qRT-PCR).The nitrosative stress(nitrosylation of proteins)was also assessed by Western Blotting.One-way Anova test with Bonferroni post hoc was used for statistical analysis.Results:STZ-diabetic rats showed a significant increase in retinal vascular permeability(展开更多
基金Supported by Grants No.NT11457 and No.NT11402(to IGA MZ CR)grant from Research project(Ministry of Health Care,Czech Republic)of the conceptual development of research organization,No.00064203(to FN Motol)
文摘Hepatocyte nuclear factor 1-β(HNF1B)defects cause renal cysts and diabetes syndrome(RCAD),or HNF1B-maturity-onset diabetes of the young.However,the hepatic phenotype of HNF1B variants is not well studied.We present a female neonate born small for her gestational age[birth weight 2360 g;-2.02standard deviations(SD)and birth length 45 cm;-2.40 SD at the 38th gestational week].She developed neonatal cholestasis due to biliary atresia and required surgical intervention(portoenterostomy)when 32-d old.Following the operation,icterus resolved,but laboratory signs of liver dysfunction persisted.She had hyperechogenic kidneys prenatally with bilateral renal cysts and pancreatic hypoplasia postnatally that led to the diagnosis of an HNF1B deletion.This represents the most severe hepatic phenotype of an HNF1B variant recognized thus far.A review of 12 published cases with hepatic phenotypes of HNF1B defects allowed us to distinguish three severity levels,ranging from neonatal cholestasis through adult-onset cholestasis to noncholestatic liver impairment,all of these are associated with congenital renal cysts and mostly with diabetes later in life.We conclude that to detect HNF1B variants,neonates with cholestasis should be checked for the presence of renal cysts,with special focus on those who are born small for their gestational age.Additionally,patients with diabetes and renal cysts at any age who develop cholestasis and/or exocrine pancreatic insufficiency should be tested for HNF1B variants as the true etiological factor of all disease components.Further observations are needed to confirm the potential reversibility of cholestasis in infancy in HNF1B mutation/deletion carriers.
文摘玻璃体切除术(pars plana vitrectomy,PPV)为增殖性糖尿病视网膜病变(proliferative diabeticretinopathy,PDR)常用治疗手段,但手术难度大、出血量多,难以有效控制,会延长手术时间、增加手术失败风险。采取有效措施优化治疗,降低手术风险是近年来的研究热点。
文摘The ‘‘omics sciences’’ (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns of genes, miRNA, proteins, and metabolites. This study aimed, through bioinformatics and systems biology, to decipher the cytokinome profile in the evolution of inflammatory processes leading to cancer. The cytokinome was defined as the totality of cytokines and their interactions in and around biological cells. The system biology approach would provide a better understanding of the complex interaction network of cytokines, especially in cancer patients. Acquired knowledge would enable health providers with tools to evaluate disease onset through progression as well as identifying innovative therapeutic strategies. Understanding the role each cytokine plays in the metabolic network is of great importance. This paper reviews our group’s ‘‘omics’’ work. In particular, it addresses the role cytokines play in liver disease in six different scenarios. The first is the role the cytokines play in chronic inflammatory diseases and cancers. The second is the significance of the cytokinome profile. The third is the role of liver cirrhosis as an inflammatory disease. The fourth is the comparison of cytokine levels evaluated in patients with chronic hepatitis C virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of type 2 diabetes. And lastly, we present a comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of hepatocellular carcinoma.
文摘A highly-fractionated garnet-bearing muscovite granite represents the marginal granitic facies of the Abu-Diab multiphase pluton in the Central Eastern Desert of Egypt. New electron microprobe analyses(EMPA) and laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS) data from garnets are reported, in order to constrain their origin and genesis. Garnet in the Abu-Diab host granite is euhedral to subhedral, generally homogeneous and, in rare cases, it shows weak zonation. The garnet contains appreciable amounts of MnO and FeO, with lesser amounts of MgO and CaO, yielding an end-member formula of Sps61–72Alm25–35Prp1–4Adr0–1. Moreover, it is depleted in large ion lithophile elements(LILE) with lower values of Ba, Nb and Sr relative to the primitive mantle. Additionally, it contains high concentrations of HREE and Y and their REE pattern shows strong negative Eu anomalies. The garnet was crystallized under relatively low temperature(646°C–591°C) and pressure(< 3 kbar) conditions. The textural and chemical features indicate that the garnet is magmatic in origin and is chemically similar to that from highly-fractionated A-type granite. It was probably formed at the expense of biotite in a highly-evolved MnO-rich magma and/or by hydroxyl complexing of Mn during the ascending fluid phases.
文摘糖尿病（Diabetes）
Pharmacist：Hello!What can I do for you？
药师：您好,请问您需要什么帮助？
Client：I want to ask you about general in-structions on how to take medication for diab etes.
顾客：我想咨询一下有关糖尿病的用药常识。
文摘Background:Overexpression of inducible nitric oxide synthase(iNOS)has been reported in diabetic retinopathy(DR).The kinin B1 receptor(B1R)is also overexpressed in DR,and can stimulate iNOS via Gαi/ERK/MAPK pathway.We previously showed that the topical administration of a B1R antagonist,LF22-0542,significantly reduces leukocyte infiltration,increased vascular permeability and overexpression of several inflammatory mediators,including iNOS in DR.Thus,the aim of this study was to determine whether the pro-inflammatory effects of B1R are attributed to oxidative stress caused by the activation of iNOS pathway in order to identify new therapeutic targets for the treatment of DR.iNOS and B1R being absent in the normal retina,their inhibition is unlikely to result in undesirable side effects.The approach will be no invasive by eye application of drops.Methods:Diabetes was induced in male Wistar rats(200-230 g)by a single intraperitoneal injection of streptozotocin(STZ,65 mg/kg b.w).One week later,rats were randomly divided into four groups(N=5)and treated for one week as follows:Gr 1:control rats treated with the selective iNOS inhibitor(1,400 W,0.06μM twice a day by eye-drops×7 days),Gr 2,STZ-diabetic rats treated with 1,400 W,Gr 3:control rats received a selective B1R agonist[Sar(D-Phe8)-des-Arg9-BK,100μg twice a week]by intravitreal injections(itrv)and treated with 1,400 W,Gr 4:STZ-diabetic rats+B1R agonist+1,400 W.At the end of treatment and two weeks post-STZ,three series of experiments were carried out to measure vascular permeability(by Evans blue dye method)and the expression of vasoactive and inflammatory mediators,including iNOS,VEGF-A,VEGF-R2,IL-1β,Cox-2,TNF-α,bradykinin 1 and 2 receptors and carboxypeptidase M/kininase 1(by Western Blotting and qRT-PCR).The nitrosative stress(nitrosylation of proteins)was also assessed by Western Blotting.One-way Anova test with Bonferroni post hoc was used for statistical analysis.Results:STZ-diabetic rats showed a significant increase in retinal vascular permeability(
