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Objective To study the clinical pathological features of Wegener's granulomatosis (WG) in middle-aged and elderly patients,and enhance understanding of this disease.Methods Totally 21 patients with WG (11 males,10 females,aged 45 to 76 years,mean age 58.1 years) in our hospial from February 1999 to July 2012 were selected.The clinical and pathological data of WG patients were retrospectively analyzed.34 biopsies including 2 autopsies from different organs were paraffin embedded and stained by hematoxylin and eosin and histochemistry.13 renal biopsies were all examined by immunofluorescence and electron microscope.Results The average time from the onset of clinical symptoms to the diagnosis was 5.3 months (from 24 days to 11.0 months).Eyes,nose and salivary glands were the most commonly involved parts at the beginning of Wegener's granulomatosis (52.4％,11 cases).The percentages of the skin,lung and renal involvement were 14.3％ (3 cases),81.0％ (17 cases) and 71.4％ (15 cases),respectively.Among 21 patients,18 patients were examined with anti-neutrophil cytoplasmic antibody (ANCA).c-ANCA was positive in 72.2 ％ patients (13 cases,13/18),p-ANCA was positive in 16.7％ patients (3 cases,3/18),and ANCA was negative in 11.1％ patients (2 cases,2/18).3 major pathological manifestations were observed:7 kinds of vasculitis including capillaritis,acute vasculitis,chronic vasculitis,fibrinoid necrosis in vasculitis,necrotizing granulomatous vasculitis,non-necrotizing granulomatous vasculitis and cicatricial vascular changes; 4 kinds of granulomatous inflammation including scattered giant cells,palisading histiocytes,poorly formed granulomas and microabscess surrounded by granulomatousinflammation;2 kinds of parenchymal necrosis including geographic necrosis and microabscess.13 kinds of histopathologic features in 3 major manifestations were found from 2 autopsies,but various kinds histopathologic features presented in small biopsy samples.Minor manifestations such as diffuse pulmonary hemorrhage were found at the periphery of WG.Conclusions The wide variation and broad spectrum of pathologic features can occur in WG.Vasculitis,granulomatous inflammation and parenchymal necrosis are the most important histopathological features.The correct diagnosis of WG requires careful correlation of pathology with complicated clinical features.
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<p><b>OBJECTIVE</b>To synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl peptidase 4 (DPP4) inhibitors and characterize their biological activities in vitro.</p><p><b>METHODS</b>Eleven analogues of carbonitrilpyrrolidine were designed and synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-1-yl)acetyl bromide with substituted phenyl piperazine pyridazinones.</p><p><b>RESULTS</b>The structures of the compounds were characterized by (1)H-NMR and MS spectra. Biological evaluation indicated that most of the compounds exhibited moderate inhibitory activities against DPP4.</p><p><b>CONCLUSION</b>The preliminary bioassay indicates that all the synthesized compounds have moderate DPP-4 inhibition activity, especially the compounds 1j and 1k with inhibition rates reaching 26.14% and 34.15% at the concentration of 1×10(5) nmol/L, respectively.</p>
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Humans , Diabetes Mellitus, Type 2 , Drug Therapy , Dipeptidyl-Peptidase IV Inhibitors , Chemistry , Drug Design , Hypoglycemic Agents , Chemistry , Pyrrolidines , ChemistryABSTRACT
Objective To observe the incidence rate of non-alcoholic fatty liver disease (NAFLD) in elderly male patients with type 2 diabetes mellitus (T2DM) and the features of pathological changes of liver. Methods The 89 cases with T2DM (T2DM group) and contemporary non-diabetic cases (control group, n=48) from 858 autopsy samples matched for gender and age were selected in the study. The histopathological changes of liver were observed by microscopy,histochemistry and immunohistochemistry. Results The incidence rates of NAFLD and nonalcoholic steatohepatitis(NASH) were 49.4% (44/89) and 14.6% (13/89) in T2DM group, 22.9 %(11/48) and 4.2% (2/48) in control group, respectively. The incidence rates of NAFLD and NASH were significantly higher in T2DM group than in control group(P＜0.01, P＜0.05). All of the NASH patients from T2DM group and one patient from control group were complicated with different stages of liver fibrosis. One patient from T2DM group was diagnosed as cirrhosis, no cirrhosis patient was found in control group. Conclusions Compared with control group, the incidence rate of NAFLD is higher and the damage of liver is more severe in T2DM group. The ratio of the progress from NAFLD to liver cirrhosis is low.
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Aim To discover specific telomerase inhibitors by high-throughput screening in the more than 2 000 strains of actinomycetes fermentation broth.Methods After verifying the three kinds of screening models for telomerase inhibitor by yeast PCR,the three yeast strains were inoculated overnight into yeast liquid culture which was lacking in histidine and contained 3-AT.Then concentration of yeast strains in culture liquid and dosage of screening sample were regulated for better adjustment to the high-throughput screening.At last the adjusted liquid culture containing yeast strain piped to 96-well plates,drug samples and control article were also added,then the yeast was incubated in the thermostat oscillator.At the same time OD_(595nm) of the yeast liquid was measured every 12 h by using Multifunctional Microplate Analyzer,and the samples whose inhibitory efficiency was over 0.45 were selected for secondary screening.Results The high-throughput screening method related to yeast three-hybrid system was effective in screening samples that had potential telomerase inhibitory ability.The initial concentration of yeast liquid OD_(595nm) was 0.04 and the best dosage of samples was 5 ml.14 active samples,whose inhibitory efficiency was over 0.45,were founded after primary and secondary screening.Conclusions High-throughput screening method related to yeast three-hybrid system is simple and stable in discovering telomerase inhibitors,and 14 new antitumor compounds are identified,which lays the foundation in the development of new anti-tumor agents.
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Objective To study the histopathological features of hepatic portal area in autopsy specimens of elderly men with type 2 diabetes mellitus (T2DM).Methods One hundred and three autopsy cases with T2DM (diabetic group) and contemporary 48 non-diabetic cases matched by gender and age (control group) were selected in the study.The histopathological changes of hepatic portal area were observed by histochemical and immunohistochemical methods.Results (1) In diabetic group, endothelial denudation, eosinophilie deposits, eccentric intimal thickening and luminal stenosis were found in hepatic interlobular artery (arteriole, the lumen diameter < 100 μm).The medial smooth muscle cells proliferated and migrated into intima, and fibroplasia occurred in adventitia.62.1% (64/103) of the patients with T2DM had microangiopathy and there was statistically significant difference between the two groups (χ2= 27.14, P< 0.01 ).(2) Hyaline collagen fiber tissues deposited around interlobular artery, interlobular vein and interlobular bile ducts, resulting in enlargement of the portal area and the secondary atrophy and disappearance of portal triad.65.0% (67/103) of the patients with T2DM had this pathological changes in the portal area and there was statistically significant difference between the two groups(χ2= 23.27,P<0.01).(3) Terminal portal area was notable.Conclusions Mieroangiopathy can be observed in the hepatic portal areas of elderly men with T2DM, which may induce the fibrotic tissue hyperplasia, the atrophy of the portal triad and the sclerosing portal area.