Clinical data of one patient diagnosed as IgG4-related retroperitoneal fibrosis was analyzed.IgG4 and retroperitoneal fibrosis were used as the key words to search literatures from PubMed and Wanfang Database.Clinical data of 27 cases with IgG4 retroperitoneal fibrosis,including clinical manifestation,diagnostic basis,therapeutic method and prognosis,which were retrieved through literatures,were analyzed.A 82-year-old male patient presented with urinary tract obstruction and renal insufficiency.Imaging examination revealed a retroperitoneal irregular lump shadow,and showed chronic inflammation of soft tissues in posterior peritoneum with fibrosis by biopsy pathology.The IgG4-positive plasmocyte infiltration was found by immunohistochemical method.The serum level of IgG4 was significantly increased,which was in accord with IgG4-related retroperitoneal fibrosis.After treatment with methylprednisolone,retroperitoneal lump shadow was obviously dissipated.The serum level of IgG4 became normal.27 cases with IgG4-related retroperitoneal fibrosis were searched through literature retrieval,with 19 confirmed cases,3 suspected cases,and 5 suspicious cases.Male accounted for 92.6％ (25/27),and the average age was 67.6 years old.The cases with the involvement of extraperitoneal organs accounted for 37.0％ (10/27).The misdiagnosis rate was 55.6％ (15/27).23 cases took effective therapy with glucocorticoids.IgG4-related retroperitoneal fibrosis is an orphan disease,which can be misdiagnosed easily.The diagnosis is made with histopathological examination and determination on the serum level of IgG4.The therapy with glucocorticoids is effective.

Objective To compare the effects of clopidogrel with or without combined with CYP3A4-metabolized statin in treating coronary artery disease (CAD) among the elderly patients.Methods The study cohort was defined as all patients were over 60 years of age and hospitalized for CAD who were prescribed clopidogrel between January 2000 and February 201 1.A total of 1021 patients were enrolled,with 178 of them prescribed clopidogrel and 843 patients were administrated clopidogrel combined with statins (CYP3A4-metabolized statins 636 and non CYP3A4-metabolized statins 207).The primary endpoint was all cause of death and the second endpoint were non-fatal myocardial infarction (MI),but hospitalized for unstable angina,stroke,transient ischemic attack,or repeated revascularization (PCI or coronary artery bypass graft).Results Among the clopidogrel group and the clopidogrel plus statins group,the incidence density of death was 6.86/1000 and 3.18/ 1000 respectively,with crude RR as 2.15(95％CI:1.39-3.33) and statistically significant (x2=3.53,P＜0.01).The incidence density of composite thromboembolic events did not show statistical significance (P＞0.05).The two groups were 1∶1 matched,after propensity score matching,clopidogrel coadministrated with statins group showed significant decrease in all cause of death,with RR as 0.42 (95％ CI:0.19-0.93),x2=7.23,P＜0.01.No significant difference was observed in deaths or composite thromboembolic events between statins via different cytochrome P450 pathways.Conclusion Clopidogrel with statin could reduce the mortality of elderly CAD patients compared with clopidogrcl without statin.The result did not show statistical significance between CYP3A4-metabolized statins or non CYP3A4-metabolized statins regarding the mortality or composite endpoint events.

This study was purposed to characterize the effect of carboxylic acid metabolite (SR26334) of clopidogrel bisulfate deprived of antiplatelet efficacy on the spectrum of gene expression in the cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and to explore the potential molecule mechanism of SR26334 impact on HUVEC. By using a Affymetrix HU133 plus 2.0 oligonucleotide microarray, the alteration of gene expression spectrum induced by SR26334 in HUVEC was detected, the real-time PCR was used to confirm the results of selected differentially expressing genes. The results indicated that total 235 including 176 up-regulated and 59 down-regulated genes were obtained with change more than 1.5-fold after SR26334 (10 µmol/L) acted on HUVEC for 48 h. SR26334 affected the expression levels of genes involved regulation of transcription, transcription, positive regulation of transcription from RNA polymerase II promoter, cell cycle, cell division, protein amino acid dephosphorylation in HUVEC. It is concluded that carboxylic acid metabolite SR26334 of clopidogrel bisulfate modulates function of endothelial cells through different pathway at gene level.
Cell Line ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; Humans ; Ticlopidine ; analogs & derivatives ; pharmacology ; Transcriptome ; drug effects

This study was purposed to investigate the effect of clopidogrel on gene expression profile of cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and explore its potential molecule mechanism. A Affymetrix U133 plus 2.0 oligonucleotide microarray was applied to detect the alteration of gene expression profile induced by clopidogrel in HUVEC. Real time RT-PCR was used to verify the result of selected differentially expressing genes. The results showed that total 508 genes (including 139 up-regulated and 369 down-regulated genes) were obtained with differential expression more than 1.5-fold after clopidogrel (10 µmol/L) acted on HUVEC for 48 h. Clopidogrel affected the expression levels of genes involved protein binding, transcription factor activity, zinc ion binding, regulation of DNA-dependent transcription, transcription, RNA splicing and so on. It is concluded that the clopidogrel modulate function of endothelial cells by regulating sets of genes through different pathway.
Cell Line ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger ; genetics ; Ticlopidine ; analogs & derivatives ; pharmacology ; Transcription, Genetic ; Transcriptome

OBJECTIVETo evaluate the effect of irbesartan on the proliferation, apoptosis, and VEGF mRNA expression of human umbilical vein cell line EA.hy926 in vitro.

METHODSThe human umbilical vein cell line EA.hyY926 were treated with various concentrations of irbesartan for 24 h. The cell proliferation after the treatment was detected by CCK8 assay, flow cytometry and FITC Annexin V/PI kit were used to detect changes in the cell apoptosis. RT-PCR was used to evaluate the expression of VEGF mRNA.

RESULTSThere were no changes in cell shape with various concentration of irbesartan. CCK-8 assay showed a greater rate of the cell proliferation in irbesartan group than that in control group with a dose-independent manner after 24 h treatment. After incubation with irbesartan, cell proliferation rate was significant (P < 0.05). FCM analysis showed no significantly changes in the cell apoptosis. Irbesartan increased the proliferation of EA.hy926 cells. At concentration of 1 x 10(-4), 1 x 10(-5), 1 x 10(-6) mol/L, VEGF mRNA expression enhanced either (P < 0.05).

CONCLUSIONIrbesartan could promote the proliferation and up-regulated VEGFmRNA expression in EA.hy926 cell line. This result suggested that in addition to antihypertensive effect, angiotensin receptor antagonist might be a novel therapeutic approach to chronic ischemic heart disease as heart failure.

Apoptosis ; drug effects ; Biphenyl Compounds ; pharmacology ; Cell Line ; Cell Proliferation ; drug effects ; Humans ; RNA, Messenger ; genetics ; Tetrazoles ; pharmacology ; Umbilical Veins ; cytology ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo scrutinize the immunohistochemical spectrum to differentiate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC) and metastatic adenocarcinoma (MAC) in the liver.

METHODSSeven antibodies including AFP, Hep Par 1, CK18, CK19, CA19-9, CD34 and pCEA were immunohistochemically stained in resected specimens of 300 HCC, 35 ICC and 30 MAC. The specificity and sensitivity of the antibodies were evaluated by comprehensive capability score (CCS), with only those with CCS > or = 8 considered as having highly diagnostic value.

RESULTSAntibodies CCS > or = 8 were observed as Hep Par 1 and CD34 in HCC, and CK19 in ICC, but none in MAC. For HCC, CCS of Hep Par 1 was higher than that of AFP (9 vs. 7) with 83.7% in sensitivity and 96.7% in specificity.

CONCLUSIONFor HCC, Hep Par 1 and CD34 can be used as the first line antibodies, AFP and pCEA as the second line ones. CK19 is the first line antibody for ICC, and CA19-9 as the second. Hep Par 1, CD34 and CK19 are definitely helpful for the routine immunohistochemical stain to differentiate HCC from ICC and MAC.

Adenocarcinoma ; chemistry ; Antibodies ; immunology ; Carcinoma, Hepatocellular ; chemistry ; Cholangiocarcinoma ; chemistry ; Humans ; Immunohistochemistry ; Liver Neoplasms ; chemistry ; Tumor Cells, Cultured

The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 2³ full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription: isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.

OBJECTIVETo investigate the relationship between monoamine oxidase A (MAOA) gene polymorphisms and schizophrenia in a Chinese Han population.

METHODSTwo hundred and twelve schizophrenic patients and 168 healthy controls were recruited according to CCMD-3. The polymorphisms of MAOA gene were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The case-control association analysis was adopted to analyze the frequencies of genotype and allele in schizophrenic patients and controls.

RESULTS(1) The genotypes of MAOA gene were consistent with Hardy-Weinberg equilibrium in patient group and control group (chi2 = 0.618, df= 2, P> 0.05; chi2 = 3.173, df= 2, P> 0.05). (2) The distributions of genotypes or alleles of MAOA genes had no significant difference between patient group and control group (P> 0.05). (3)Divided by sex, the frequency of CT genotype in male patients was higher than that in male controls (chi2 = 7.654, P= 0.022). (4) There were no significant differences of genotypic and allelic distribution in MAOA genes between schizophrenic patients with positive family history and schizophrenic patients with negative family history and among different clinical subtypes in schizophrenic patients (P> 0.05).

CONCLUSIONNo association between MAOA gene and schizophrenia is found in Chinese Han population, but CT genotype is likely to be a susceptible factor of male schizophrenia.

Adolescent ; Adult ; Alleles ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Monoamine Oxidase ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Schizophrenia ; genetics ; Young Adult

BACKGROUNDAngiogenesis occurs commonly in various physiological and pathological processes. Improving blood supply through promoting angiogenesis is a novel approach for treating ischemic diseases. Angiotensin II type 1 receptor blockers (ARBs) dominate the management of hypertension, but evidence of their role in angiogenesis is contradictory. Here we explored the angiogenic effects of ARBs through characterizing gene expression of the human umbilical vein endothelial cell line EA.hy926 exposed to irbesartan.

METHODSThe human umbilical vein endothelial cell line EA.hy926 was grown for 72 hours after treatment with different concentrations of irbesartan. The cell proliferative capacity was assessed by CCK8 assay at 24, 48 and 72 hours. Gene expression levels in EA.hy926 cells responding to irbesartan were measured under optimal proliferation conditions by microarray analysis using Affymetrix U133 plus 2.0. The differential expression of genes involved in angiogenesis was identified through cluster analysis of the resulting microarray data. Quantitative RT-PCR and Western blotting analyses were used to validate differential gene expression related to the angiogenesis process.

RESULTSIn the 10(-4), 10(-5), 10(-6) mol/L treatment groups, cell proliferation studies revealed significantly increased proliferation in EA.hy926 cells after 24 hours of irbesartan treatment. However, after 48 and 72 hours of treatment with different concentrations of irbesartan, there was no significant difference in cell proliferation observed in any treatment group. We selected the group stimulated with irbersartan at a concentration of 10(-6) mol/L for microarray experiments. Statistical analysis of the microarray data resulted in the identification of 56 gene transcripts whose expression patterns were significantly correlated, negatively or positively, with irbesartan treatment. Cluster analysis showed that these genes were involved in angiogenesis, extracellular stimulus, binding reactions and skeletal system morphogenesis. Of these 56 genes we identified seven genes (VEGF, KDR, PTGS2, PLXND1, ROBO4, LMO2, and COL5A1) involved in the angiogenesis process. qRT-PCR analysis of these genes confirmed the microarray results. Protein expression of three VEGF pathway genes (VEGF, KDR, and PTGS2) was further confirmed by Western blotting.

CONCLUSIONSOur study showed that irbesartan may induce angiogenic effects in vascular endothelial cells. It suggested that the mechanism of angiogenic effects of ARBs might be attributed to the signaling cascade from angiotensin receptors in the VEGF pathway. It also provided evidence indicating that ARBs could be used as a novel therapeutic approach to treat chronic ischemic heart disease as well as anti-hypertensive agents.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Antihypertensive Agents ; pharmacology ; Biphenyl Compounds ; pharmacology ; therapeutic use ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Gene Expression Profiling ; Humans ; Myocardial Ischemia ; drug therapy ; Neovascularization, Physiologic ; drug effects ; Tetrazoles ; pharmacology ; therapeutic use

OBJECTIVETo characterize if irbesartan regulates vascular inflammatory gene expression profiles related to atherosclerosis in EA.hy926 cells.

METHODSHuman umbilical vein endothelial cell line EA.hy926 cultured in vitro was incubated with irbesartan (1×10(-6) mol/L) for 24 h. The total RNA was extracted from the cells for gene expression profiling. The DAVID Gene Functional Classification Tool was used to analyze the disease- and function-related genes in the cells. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the genes showing differential expression after irbesartan treatment. The protein levels of angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) were tested by Western blotting.

RESULTSCompared with the control cells, 56 genes were found to show marked changes following irbesartan treatment, including 39 up-regulated and 17 down-regulated genes. Disease analysis suggested that these genes were related to such diseases as coronary atherosclerosis, myocardial infarction, and colorectal cancer. Eight genes, namely MMP2, PTGS2, PECAM1, SELP, SELL, CYP1A1, MMRN1, and HSPA1A, were involved in atherosclerosis and myocardial infarction. Verification by RT-PCR produced a result consistent with the gene array result. AT1R was down-regulated while AT2R up-regulated in irbesartan-treated cells.

CONCLUSIONIrbesartan regulates the inflammatory gene expressions related to atherosclerosis in EA.hy926 cells. These inflammatory factors may promote destabilization of atherosclerotic plaque possibly in relation to AT2R overexpression.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Atherosclerosis ; genetics ; pathology ; prevention & control ; Biphenyl Compounds ; pharmacology ; Cell Line ; Cytoprotection ; Gene Expression Profiling ; Human Umbilical Vein Endothelial Cells ; drug effects ; pathology ; Humans ; Inflammation ; genetics ; Receptor, Angiotensin, Type 1 ; genetics ; Receptor, Angiotensin, Type 2 ; genetics ; Tetrazoles ; pharmacology