Analysis of NR2F1 gene variant in a child with optic atrophy and global developmental delay / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with optic atrophy and global developmental delay.@*METHODS@#A child who had presented at the Guangzhou Women and Children's Medical Center in January 2022 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a nine-month-old female, had manifested dysopia and global developmental delay. Genetic testing revealed that she has harbored a de novo c.425G>C (p.Arg142Pro) variant of the NR2F1 gene, which has been associated with Bosch-Boonstra-Schaaf syndrome. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PM1+PM2_Supporting+PM5+PP3+PP4).@*CONCLUSION@#The c.425G>C (p.Arg142Pro) variant of the NR2F1 gene probably underlay the pathogenesis in this child. Above finding has enriched the genotypic and phenotypic spectrum of the NR2F1 gene.

Genetic analysis of a child with developmental disorder and epilepsy due to a homozygous variant of PIGW gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring global developmental disorder with epilepsy.@*METHODS@#A child who had presented at Guangzhou Women and Children's Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c.821T>C (p.Leu274Pro) missense variant of the PIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance.@*CONCLUSION@#The homozygous c.821T>C (p.Leu274Pro) variant of the PIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.

Clinical analysis of relapsed demyelinating disease associated with myelin oligodendrocyte glycoprotein antibody in children / 中华实用儿科临床杂志

Objective@#To investigate the clinical characteristics, treatment and prognosis of relapsed demyeli-nating disease (RDD) associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs) children in southern China.@*Methods@#Children with RDD associated with MOG abs at Department of Neurology in Guangzhou Women and Children′s Medical Center from January 2015 to December 2018 were retrospectively analyzed.The annualized relapse rates (ARRs) and expand disability status scale (EDSS) were used to assess the recurrence frequency and neurological dysfunction respectively.@*Results@#Ten children were included with the age of (6.4±3.6) years old, and male to female ratio was 4∶6.(1)Clinical phenotype: all children had 24 episodes during follow-up, with acute disseminated encephalomyelitis (ADEM)(7/10 cases) and neuromyelitis optica spectrum disorders (NMOSD)(3/10 cases) on the first episode.Among 14 recurrent episodes, ADEM (9/14 times) was the most common, followed by optic neuritis(ON)(3/14 times)and brainstem encephalitis (2/14 times). By the final follow-up, the final diagnosis was multiphasic disseminated encephalomyelitis(MDEM)(6/10 cases), NMOSD(3/10 cases), ADEM-ON(1/10 case), respectively.(2)Laboratory examination: all the children had positive serum MOG abs in the acute stage.The serum MOG abs titer high group(≥1∶640)(6 cases)on the first episode complicated ON (3 cases) and long segment myelitis (3 cases) more common than those of low group(1∶320)(4 cases). (3)Imaging changes: 25 times of bain magnetic resonance imaging (MRI) were performed in the acute stage, MRI changes mostly involved the cortex and subcortical white matter.Four cases had abnormal spinal cord MRI.(4)Treatment and prognosis: intravenous methylprednone (IVMP) combined with intravenous immunoglobulin (IVIG) were administrated in acute stage.Rituximab (2/10 cases), mycophenolate mofetil (4/10 cases), IVIG (2/10 cases) monthly and low dose prednisone orally (2/10 cases) were given respectively in maintains stage.ARRs decreased from 1.4 to 0 and EDSS score improved significantly after these treatments above.Seven cases had residual neurological dysfunction with 3 cases of NMOSD, 3 cases of MDEM and 1 case of ADEM-ON, including motor dysfunction, learning disability and inattention, symptomatic epilepsy and visual impairment.@*Conclusions@#ADEM is the most common form of RDD associated with MOG abs in children.Those with high serum MOG abs titer on the first episode are prone to have ON or long segment myelitis.Immunomodification therapy is effective in the relapsed patients, residual neurological sequelae were related to the type of repeated demyelination.

Clinical analysis of relapsed demyelinating disease associated with myelin oligodendrocyte glycoprotein antibody in children / 中华实用儿科临床杂志

Objective To investigate the clinical characteristics,treatment and prognosis of relapsed demyelinating disease (RDD) associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs) children in southern China.Methods Children with RDD associated with MOG abs at Department of Neurology in Guangzhou Women and Children's Medical Center from January 2015 to December 2018 were retrospectively analyzed.The annualized relapse rates (ARRs) and expand disability status scale (EDSS) were used to assess the recurrence frequency and neurological dysfunction respectively.Results Ten children were included with the age of (6.4 ± 3.6) years old,and male to female ratio was 4 ∶ 6.(1)Clinical phenotype:all children had 24 episodes during follow-up,with acute disseminated encephalomyelitis (ADEM)(7/10 cases) and neuromyelitis optica spectrum disorders (NMOSD)(3/10 cases) on the first episode.Among 14 recurrent episodes,ADEM (9/14 times) was the most common,followed by optic neuritis(ON) (3/14 times) and brainstem encephalitis (2/14 times).By the final follow-up,the final diagnosis was multiphasic disseminated encephalomyelitis (MDEM) (6/10 cases),NMOSD (3/10 cases),ADEM-ON (1/10 case),respectively.(2) Laboratory examination:all the children had positive serum MOG abs in the acute stage.The serum MOG abs titer high group(≥1 ∶ 640) (6 cases)on the first episode complicated ON (3 cases) and long segment myelitis (3 cases) more common than those of low group (1 ∶ 320) (4 cases).(3)Imaging changes:25 times of bain magnetic resonance imaging (MRI) were performed in the acute stage,MRI changes mostly involved the cortex and subcortical white matter.Four cases had abnormal spinal cord MRI.(4)Treatment and prognosis:intravenous methylprednone (IVMP) combined with intravenous immunoglobulin (IVIG) were administrated in acute stage.Rituximab (2/10 cases),mycophenolate mofetil (4/10 cases),IVIG (2/10 cases) monthly and low dose prednisone orally (2/10 cases) were given respectively in maintains stage.ARRs decreased from 1.4 to 0 and EDSS score improved significantly after these treatments above.Seven cases had residual neurological dysfunction with 3 cases of NMOSD,3 cases of MDEM and 1 case of ADEM-ON,including motor dysfunction,learning disability and inattention,symptomatic epilepsy and visual impairment.Conclusions ADEM is the most common form of RDD associated with MOG abs in children.Those with high serum MOG abs titer on the first episode are prone to have ON or long segment myelitis.Immunomodification therapy is effective in the relapsed patients,residual neurological sequelae were related to the type of repeated demyelination.

Changes of Peripheral Leukocyte’s Telomere Length in Patients of Premature Coronary Artery Disease With Influencing Factors / 中国循环杂志

Objective: To explore the changes of peripheral leukocyte’s telomere length (LTL) in patients of premature coronary artery disease (PCAD) with inlfuencing factors. Methods: Our research was conducted in 2 sets of groups, by coronary artery condition: PCAD group,n=128 including 88 patients with ACS, 40 with SCAD and Non-CAD group,n=128 subjects; by age status: the age≤30 years, 31-40 years, 41-50 years, 51-60 years had 2, 14, 65, 47 patients in each group respectively. Peripheral LTL was detected by lfuorescent quantitative analysis, the relationship between LTL and PCAD with inlfuencing factors were studied by Spearman correlation analysis. Results: In PCAD group, compared with SCAD patients, ACS patients had more male gender, higher Gensini score, lower T/S ratio and shorter LTL, allP<0.05. Compared with Non-CAD group, PCAD group had decreased T/S ratio (0.88 ± 0.86) vs (1.10 ± 0.57),P<0.05. T/S ratio was negatively related to age in both PCAD group (r=-0.275,P=0.002) and Non-CAD group (r=-0.316,P=0.000). Spearman correlation study presented that in PCAD group, LTL was negatively related to hyperlipidemia (r=-0.415,P=0.049) and diabetes (r=-0.472,P=0.036); multi linear regression analysis indicated that in PCAD group, LTL was negatively related to age (B=-0.023,P=0.038) and in Non-CAD group, LTL was negatively related to age (B=-0.027,P=0.000), smoking (B=-0.278,P=0.012), HDL-C (B=-0.297,P=0.046). Conclusion: PCAD had more male ACS patients with shorter LTL and severer coronary lesions; LTL was negatively related to hyperlipidemia and diabetes, age was an important inlfuencing factor for LTL shortening.

Relationship Between Plasma Level of Asymmetric Dimethylarginine and Coronary Artery Ectasia in Relevant Patients / 中国循环杂志

Objective: To investigate the relationship between plasma level of asymmetric dimethylarginine (ADMA) and coronary artery ectasia in relevant patients. Methods: A total of 72 patients received coronary angiography (CAG) in our hospital were studied and the patients were divided into 3 groups: Coronary ectasia group, Coronary stenosis group and Normal coronary group.n=24 in each group. Plasma levels of ADMA, symmetric dimethylarginine (SDMA) and L-arginine (Arg) were measured by HPLC-MS/MS methods. The relationship between ADMA and CAD was examined by Logistic regression analysis. Results: Plasma level of ADMA in Coronary ectasia group (0.437 ± 0.098) μmol/L and Coronary stenosis group (0.456 ± 0.088) μmol/L were higher than that in Normal coronary group (0.381 ± 0.057) μmol/L,P<0.05. The ratio of Arg/ADMA in Coronary ectasia group (208.54 ± 61.52) and Coronary stenosis group (220.00 ± 104.82) were lower than that in Normal coronary group (254.26 ± 76.22),P<0.05. Logistic regression analysis presented that with adjusted age, gender, smoking, family history of CAD and LDL-C level, and plasma ADMA was still related with CAD (Partial regression coefifcient 9.469, P=0.011). Conclusion: Plasma levels of ADMA were higher in patients with coronary artery ectasia/stenosis than those with normal coronary artery; while ADMA levels were similar between the patients with coronary ectasia and stenosis. Plasma ADMA level was the independent risk factor of CAD.

Analysis of traditional cardiovascular risk factors in patients with systemic lupus erythematosus / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluation the prevalence of hypertension, diabetes, dyslipidemia in systemic lupus erythematosus (SLE) patients, and investigate the factors that affecting lipid levels in SLE patients.</p><p><b>METHODS</b>A total of 540 adult SLE patients hospitalized in Peking Union Medical College Hospital from March 2010 to March 2013 were retrospectively included (SLE group), and 1 080 gender and age matched (1: 2) healthy controls were selected from our medical examination center (control group). The prevalence rate of hypertension, diabetes, dyslipidemia and the levels of serum lipid were compared between the two groups, the factors affecting lipid levels in SLE patients were also analyzed.</p><p><b>RESULTS</b>The percentage of hypertension, diabetes, dyslipidemia, elevated total cholesterol (TC), elevated triglyceride (TG), decreased high density lipoprotein cholesterol (HDL-C) and elevated low density lipoprotein cholesterol (LDL-C) in SLE patients were significantly higher than those in healthy controls (all P < 0.01) . Compared with the control group, SLE patients had significantly higher TC, TG, LDL-C levels and significantly lower HDL-C levels (all P < 0.01) . Multifactor regression analysis showed that TC and LDL-C levels were positively correlated with lupus nephritis (β = 0.695,0.437), corticosteroids therapy (β = 1.195, 0.715), complement C4 levels (β = 4.817, 3.382) and 24 hours urine protein content (β = 0.112, 0.078) (all P < 0.01) , but negatively correlated with serum albumin (Alb) (β = -0.107, -0.077) and high sensitive C reactive protein (hsCRP) levels (β = -0.021, -0.014) (all P < 0.01). TG levels were positively correlated with lupus nephritis (β = 0.359) and 24 hours urine protein content (β = 0.045) (both P < 0.05), negatively correlated with male gender (β = -0.605), age (β = -0.014) and Alb levels (β = -0.053) (P < 0.01 or 0.05). HDL-C levels were positively correlated with age (β = 0.007), lupus nephritis (β = 0.188), corticosteroids therapy (β = 0.342), consecutive 30 days cumulative corticosteroids dose before serum lipid were measured (β<0.001), and complement C3 levels(β = 0.351) (all P < 0.01) , negatively correlated with hsCRP levels (β = -0.005, P < 0.01). Serum lipid levels did not correlate with disease duration, disease activity, corticosteroids therapy time, corticosteroids daily dose before serum lipid measurement, serum creatinine levels and erythrocyte sedimentation rate (ESR) (all P > 0.05).</p><p><b>CONCLUSION</b>The prevalence rate of hypertension, diabetes and dyslipidemia in SLE hospitalized patients are significantly higher compared to normal controls and lipid levels of SLE patients are related to various SLE disease factors.</p>

Echocardiographic features and predictors of pulmonary hypertension in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To analyze the risk factors of pulmonary hypertension in patients with systemic lupus erythematosus (SLE-PH).Methods Echo data of 598 SLE patients were collected,clinical characteristics of 107 suspected SLE-PH (PASP ≥40 mmHg,estimated by Echo) and 64 suspected moderate to severe PH (PASP ≥50 mmHg) were retrospectively analyzed.T-test,x2-test and Logisticregression were used for statistical analysis.Results Out of 598 patients 70.7％(423 patients) had abnormal Echo findings,and pericardial effusion in 45.5％(272 cases),valvular insufficiency in 31.3％(187 cases),suspected PH in 17.9％(107 cases),left ventricular enlargement in 5.9％(35 cases),left ventricular hypertrophy in 4.3％(26cases).In addition 1.7％ had mitral valve prolapse,1.5％ had mitral valve vegetation,and right ventricular enlargement in 6.5％(39 cases),LVEF＜50％ in 6.0％(36 cases),right ventricular systolic dysfunction in 2.2％(13 cases).Logistic regression analysis showed Raynaud's phenomenon (OR=3.205,95％CI:1.911-5.375,P=0.000),thrombocytopenia (OR=1.680,95％CI:1.049-2.689,P=0.031),hyperuricemia (OR=3.643,95％CI:2.154-6.164,P=0.000),and anti-U1RNP antibody positivity (OR=1.777,95％CI:1.099-2.874,P=0.019)were independent risk factors for suspected SLE-PH,fever (OR=0.576,P=0.029)and rash (OR=0.558,P=0.017) were independent protective factors for suspected SLE-PH.SLE duration (OR=1.145,95％CI:1.016-1.290,P=0.026) and Raynaud's phenomenon (OR=3.371,95％CI:1.126-10.086,P=0.030)were independent risk factors for suspected moderate to severe PH,nephritic syndrome (OR=0.042,P=0.009) was the in dependent protective factor for suspected moderate to severe PH.Conclusion Cardiac involvement is common in SLE patients.Screening for PH should be considered in SLE patients with thrombocytopenia,hyperuricemia,anti-U1RNP antibody positivity,particularly with Raynaud's phenomenon.

The clinical manifestations and angiographic characteristics of coronary artery ectasia / 中华内科杂志

Objective To retrospectively analyze the clinical manifestations of coronary artery ectasia and its angiographic characteristics. Methods Twenty-five patients who underwent coronary angiography were diagnosed as coronary artery ectasia from January 2005 to December 2007. 25 cases of coronary artery atheresclerosis were also included and 25 cases with normal coronary arteriography in the same period were taken as control. Results Most of the patients were male (72%). Only three patients had diabetes and thirteen patients had hypertension. All the patients with coronary artery ectasia were admitted for chest pain. Nine of them showed abnormal ST changes and four elevated ST in ECG. Coronary artery ectasia was associated with slow coronary flow in 9 patients and coronary stenosis in 4 patients. The frequency of arterial involvement, in descending order, was right coronary artery in 76%, left anterior descending artery in 60%, left circumflex artery in 48% and left main artery in 8%. Ectasia affected only one major vessel was found in 44%, and all three vessels in 36%. As compared with the patients with coronary artery atherosclerosis and patients with normal coronary artery, patients with CAE had a lower prevalence of diabetes (12%), and there were no other significant statistics in clinical demography and other risk factors such as hypertension and dyslipidemia. Conclusions Coronary artery ectasia was prevalent in males and diabetes was less frequent. The RCA was the most commonly affected vessel and most of the patients had single vessel involvement.

Impaired cholesterol efflux from macrophages of patients with type 2 diabetes mellitus is associated with the decreased expression of ABCG1 / 基础医学与临床

Objective To identify potential linkage of cholesterol efflux with the expressions of ATP-binding cas-sette receptor A1 (ABCA1), ABCG1 and scavenger receptor B1 (SR-B1) in monocytes derived macrophages of patients with type 2 diabetes mellitus. Methods and Results Blood was collected from subjects with or without type 2 diabetes mellitus. Peripheral blood monocytes were differentiated for 72 hours into macrophages, and cholesterol efflux assays, Real-time quantitative PCR and western blot were performed. Macrophages from patients with type 2 diabetes mellitus showed a reduction in cholesterol efllux. The mRNA and protein expressions of ABCG1 in macrophages from patients with type 2 diabetes mellitus were significantly reduced. In contrast, the expression of ABCA1 and SR-B1 was not significantly different in both control subjects and diabetic patients. In addition, cellular cholesterol efflux from macrophages to autologous serum and pool serum was significantly correlated with the expression of ABCG1. Conclusion ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus. This impaired cholesterol efflux significantly correlates with decreased expression of ABCG1.

CRP promotes lectin-like oxidized low density lipoprotein receptor-1 expression on THP-1 derived macrophages / 基础医学与临床

Objective To explain the effects of C-reactive protein(CRP) on lectin-like oxidized low density lipoprotein receptor-1 expression on THP-1 derived macrophages and the related signal transduction pathways.MethodsTHP-1 cells were differentiated into macrophages with the stimulation of PMA.THP-1 derived macrophages were incubated with CRP and co-incubated with inhibitors of NF-?B、AP-1 and MARK signal transduction pathways.The expression of LOX-1 antigen and mRNA was analyzed by ELISA and RT-PCR.Results CRP stimulated the expression of LOX-1 antigen and mRNA on macrophages in a dose-dependent manner.NF-?B inhibitor BAY11-7085 suppressed the inducible effects of CRP on LOX-1 expression.Conclusion CRP increased LOX-1 expression on THP-1 derived macrophages at transcription and post-transcription levels.The NF-?B signal transduction pathway may be involved in such process.

Expressions of tissue factor and tissue factor pathway inhibitor in the atherosclerotic plaque / 基础医学与临床

Objective To observe the expression and location of TF and TFPI in femoral artery atherosclerotic plaque.Methods We detected the expressions and locations of TF and TFPI in femoral artery atherosclerotic plaque by immunohistochemical and double-stain immunohistochemical method.We detected TF mRNA and TFPI mRNA expressions in atherosclerotic plaque by RT-PCR,with the normal umbilical artery as a control.ResultsThe normal umbilical artery contained little TF,TFPI and their mRNA in the adventitia.A great deal of TF,TFPI and their mRNA were found in the tunica intima of the femoral artery atherosclerotic plaque.Conclusion Expression of TF,TFPI and their mRNA of all types of cells and stroma in the proliferative tunica intima.

Relationship between sES、MMP-9 and coronary artery dilation / 基础医学与临床

Objective To investigate the relationship between inflammatory factors, coronary artery dilation, and their clinical significance. Methods The cases undergone coronary angiography in our hospital last year were collected and divided into three groups: the first one included 11 patients whose angiography showed coronary artery dilation, the second group included 35 cases of atherosclerosis, and the third includes 24 cases with normal angiography. sES, MMP9 and TIMP1 were measured by ELISA method. Results Patients with coronary artery dilation were found to have significantly higher sES and MMP-9 level in comparison with atherosclerosis group and normal group[(153.7?152.7)ng/L,(90.1?54.2)ng/L,(76.5?37.2)ng/L, respectively](P

Basic fibroblast growth factor induces the differentiation of human bone mesenchymal stem cells into cardiomyogenic cells in vitro / 基础医学与临床

Objective To study the potential of bFGF to promote human bone marrow derived MSCs to differentiate into cardiomyogenic cells, and its effect on proliferation of MSCs. Methods MSCs isolated from adult human bone marrow were cultured in four different systems. Group A: medium with 5-aza. Group B: medium with bFGF. Group C: medium with 5-aza+bFGF. Control group: medium alone. The morphological changes of MSCs were observed. Then immunocytochemistry staining against ?-actin,cTnT,and Connixin43 was performed. The expression of Nkx2.5, GATA-4 and cTnT was detected by semi-quantitative RT-PCR. The proliferation of MSCs in different groups was measured by MTT. Results The MSCs in both group A and C partially differentiated into myogenic cells and expressed proteins of ?-actin,cTnT,and connixin43. In group A and group C, the mRNA level of Nkx2.5,GATA-4 and cTnT was higher than that of control group. In group B, mRNA level of Nkx2.5 and GATA-4 was higher than that of control group. As compared with the control group, cell proliferation was faster in group B than in group A and C. And the proliferation was faster in group C than in group A. Conclusion bFGF can promote the proliferation of MSCs significantly. When combining with 5-aza, bFGF can promote MSCs to differentiate into cardiomyogenic cells more effectively.

Effect of ATP-binding cassette transporter A1 on cholesterol efflux from cells / 基础医学与临床

Objective To investigate the potential change of cellular cholesterol efflux and the functional changes of ABCA1 on macrophages from diabetes animals. Methods High energy diet was given to golden hamster to make animal model of hyperlipidemia. Diabetes was induced by a single intraperitoneal injection of STZ (30 mg/kg). Macrophages were isolated and incubated with apoA-I or 8-br-cAMP in vitro. Cellular cholesterol content was measureal before and after treatment by HPLC. Results Intracellular cholesterol content of diabetic animals was higher than that in high energy diet and normal controls. Expression of ABCA1 mRNA was upregulated in diabetic group after incubation with apoA-I and cAMP. When macrophages were incubated with apoA-I, cholesterol efflux increased with the prolongation of incubation time.The amount of intracellular cholesterol efflux in 3 groups of animals showed the following relationship: diabetic animals exceed high energy diet fed animals, and the latter exceeds normal animals. Conclusion Intracellular lipid efflux depends mainly on the presence of extracellular apoA1 as well as membrane ABCA1 protein. The deposition of cholesterol in the macrophage of diabetic and insulin resistant animals may be related to the characteristic changes of quantity and function of apoA1 in these animals.

Effect of MMT on reducing the transmission of HIV among IDUs / 中国艾滋病性病

Objective To study the effect of methadone maintenance treatment(MMT) on reducing HIV infection among injecting drug users(IDUs) in Yueyang city of Hunan province.Methods Local IDUs were provided with MMT along with peer education and behavior interventions,and they were tested for HIV antibody to evaluate the effect of MMT after one year treatment.Results Of the 113 IDUs who were negative at the entry,none turned to be positive after one year treatment and the negative partners of 22 IDUs with positive HIV antibody remained negative one year later,and the negative rate of urine test maintained at 76.10%.Conclusion MMT combined with peer education and behavior interventions will decrease the use of heroin,prevent HIV infection among IDUs and reduce their partners' susceptibility to HIV.

Differentiation of rats bone marrow mesynchymal stem cells into cardiomyogenic cells with pacemaking function / 基础医学与临床

Objective To find the way of inducing the bone marrow mesynchymal stem cells(MSCs)into cardiac cells with pacemaking function in vitro.Methods Dissociate the rat MSCs and induce them with 5AZA,bFGF+EGF,HGF,SCF and lysate of the sinoatrial cells respectively.The morphological changes were observed,and the expressing of protein cTnT,connexin 43 and HCN2/4 were analyse by immunohistologic and flowcytometry techniques.The pacmaking current If were evaluted by patch clamp techniques.Results All the methods can induce the bone marrow MSCs to differentiate into cardiac cells,which expressing cardiac cell specific protein and HCN2.Cells induced by 5AZA,bFGF+EGF and SAN CMs show higher rate of HCN2 expressing(22.9%,22.3%,11%).The cells of these groups have the pacmaking current If.Conclusion Lysate of the sinoatrial cells are ideal methods of inducing the bone marrow MSCs to differentiate into cardiac cells with pacemaking function in vitro.HCN is a promising marker protein to select pacmaking cells out of the differentiated cells.

Impaired cholesterol efflux from macrophages of patients with type 2 diabetes mellitus is associated with the decreased expression of ABCG1 / 基础医学与临床

Objective To identify potential linkage of cholesterol efflux with the expressions of ATP-binding cassette receptor A1(ABCA1),ABCG1 and scavenger receptor B1(SR-B1) in monocytes derived macrophages of patients with type 2 diabetes mellitus.Methods and Results Blood was collected from subjects with or without type 2 diabetes mellitus.Peripheral blood monocytes were differentiated for 72 hours into macrophages,and cholesterol efflux assays,Real-time quantitative PCR and western blot were performed.Macrophages from patients with type 2 diabetes mellitus showed a reduction in cholesterol efflux.The mRNA and protein expressions of ABCG1 in macrophages from patients with type 2 diabetes mellitus were significantly reduced.In contrast,the expression of ABCA1 and SR-B1 was not significantly different in both control subjects and diabetic patients.In addition,cellular cholesterol efflux from macrophages to autologous serum and pool serum was significantly correlated with the expression of ABCG1.Conclusion ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus.This impaired cholesterol efflux significantly correlates with decreased expression of ABCG1.

Alteration of NO,ET-1,MMP-9 and TIMP-1 plasma levels in coronary artery stenosis and ectasia / 基础医学与临床

Objective To explore the mechanisms responsible for different coronary artery lesions with involvement of nitric oxide(NO),endothelin-1(ET-1),matrix metalloproteinases-9(MMP-9) and the matrix metalloproteinase inhibitor-1(TIMP-1).Methods The cases undergone coronary anography were collected and divided into three groups:group A,30 patients with the coronary artery ectasia(7 cases of simple coronary artery ectasia;18 cases of the coronary artery ectasia coexisting a small amount of plaque);group B,38 patients with coronary atherosclerosis;group C,32 patients with with normal angiograph(14 cases of coronary artery completely normal;18 cases with a small amount of coronary plaque only).Plasma NO,ET-1,MMP-9 and TIMP-1 level were measured by ELISA method.Results There are significant differences among three groups on NO level,MMP-9 levels,NO/ET-1 and MMP-9/TIMP-1(P

Effects of high-density lipoprotein and lipoprotein-deficient serum on intracellular cholesterol efflux in patients with type 2 diabetes mellitus / 基础医学与临床

Objective To examine the effects of high-density lipoprotein(HDL) and lipoprotein-deficient serum(LPDS) isolated from patients with type 2 diabetes mellitus on cholesterol efflux through human skin fibroblast(HSF) and human hepatoma cell line(HepG2).Methods and Results Blood was collected from 13 patients with type 2 diabetes mellitus and 17 healthy volunteers,HDL and LPDS were isolated.Cholesterol efflux assays,RT-PCR and Western blot were performed with HSF and HepG2 cells.The HepG2 cells showed a high expression of scavenger receptor B1(SR-B1) and lack of functional ATP-binding cassette receptor A1(ABCA1) and ATP-binding cassette receptor G1(ABCG1) while HSF cells express SR-B1 at very low level and have a high expression of ABCA1 pretreated with 22-OH cholesterol.The cholesterol efflux from HepG2 cells to HDL isolated from patients with diabetes decreased significantly as compared to controls.However,cholesterol efflux from HSF cells to LPDS was not different between groups.Conclusion The function of HDL involving cholesterol efflux in type 2 diabetes mellitus was impaired while cholesterol efflux induced by LPDS from HSF cells was maintained,suggesting that HDL plays a critical role in mediation of intracellular cholesterol accumulation and progression of atherosclerosis inpatients with type 2 diabetes.