2008年·第121卷第03期

Abstract：Background Myocardial perfusion associates with clinical syndromes and prognosis.Adenosine could improve myocardial perfusion of acute myocardial infarction within 6 hours,but few data are available on late perfusion of myocardial infarction (MI).This study aimed at quantitatively evaluating the value of intracoronary adenosine improving myocardial perfusion in late reperfused MI with myocardial contrast echocardiography(MCE).Methods Twenty-six patients with anterior wall infarcts were divided randomly into 2 groups:adenosine group(n=12) and normal saline group(n=14).Their history of myocardial infarction was about 3-12 weeks.Adenosine or normalsaline was given when the guiding wire crossed the lesion through percutaneous coronary intervention(PCI),then the balloon was dilated and stent(Cypher/Cypher select)was implanted at the lesion.Contrast pulse sequencing MCE with Sonovue contrast via the coronary route was done before PCI and 30 minutes after PCI.Video densitometry and contrast filled-blank area were calculated with the CUSQ off-line software.Heart function and cardiac events were followed up within 30 days.Results Perfusion in the segments of the criminal occlusive coronary artery in the adenosine group was better than that in the saline group(5.71±0.29 vs 4.95±1.22,P＜0.05).Ischemic myocardial segment was deminished significantly afterPCI,but the meliorated area was bigger in the adenosine group than in the saline group((1.56±0.60)cm2 vs(1.02±0.56) cm2,P＜0.05).The video densitometry in critical segments was also improved significantly in the adenosine group (5.53±0.36 vs 5.26±0.35,P＜0.05).Left ventricular ejection fraction(LVEF)was improved in all patients after PCI,but EF was not significant between the two groups((67±6)% vs(62±7)%,P＞0.05).There was no in-hospital or 30-day major adverse cardiac event(MACE)in the adenosine group but 3 MACE in the saline group in 30 days after PCI.Conclusions Adenosine could improve myocardial microvascular perfusion in the late reopening of an occluded infarct reIaled artery(3 to 12 weeks after AMI)and clinical outcome in the follow-up period,and myocardial microvascular perfusion is a powerful predictor of clinical events。

Abstract：Background Total arterial revascularization (TAR) was widely utilized in coronary artery bypass grafting (CABG) as a result of its better long-term effect compared with vein grafts.Of the arterial conduits,radial artery (RA) gained popularity for its easy availability and reported long-term patency.Thus,the objective of this study was to investigate the effect of RA in TAR in CABG.Methods From January 2000 to December 2006,85 patients (56 male and 29 female) at a mean age of 57.0±5.2 years,underwent TAR in CABG RA and left internal mammary artery (LIMA) with composite Y or T and seauential grafting techniques were used.Post-operative complications were recorded and follow-up was performed.Results Eighty-five LIMA and 149 RA grafts including 21 single and 64 bilateral RA were collected.A total of 87 distal anastomoses were done with the LIMA and another 152 were done with the RA,with the mean number of diStal anastOmosis per patient of 2.81±0.47.The proximal RA ends were anastomsed directly to the aorta in 140 grafts with Y or T graft off in situ LIMA in 9,Yor T graft off Rain 9.The distal end was anastomsed to right coronary artery system in 92,to Obtuse margma in 46,to diagonal in 19 and to ramous intermedius in 5.Nine sequential anastomoses were Derformed with RA.Nine composite Y or T grafts were constructed with RA and LIMA while another 9 were constructed with RA and RA.One (1.2%) patient died,3 patients (3.5%) experienced acute renal failure and 2 (2.4%) developed stroke.All patienfs were still alive and no patient had evidences of newly occurred myocardial infarction or angina after a mean tollow-up of 36.5±4.1 months (6-67 months).Postoperatively at 6 month,mean left ventricular ejective fraction was increased to 0.49±0.09,compared with that of 0.43±0.11 preoperatively (P=0.027).Postoperative mean New York Heart Association class was 2.5±0.5,compared with that of 3.0±0.4 preoperatively (P=0.003).Conclusions TAR with arterial conduits of which RA was mainly used was proved in this study to be effective and safe in CABG。

Abstract：Background CD4+CD25+ regulatory T cells (Tregs) mediate immune suppression through cell-cell contact with surface molecules,particularly cytotoxic T lymphocyte-associated antigen 4 (CTLA-4),glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR),and transforming growth factor β(TGF-β),but little is known about the exact role of Tregs in the pathogenesis of asthma.This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells-derived Tregs in patients with atopic asthma and healthy subjects,and to investigate the effect of inhaled corticosteroid on them.Methods The expression of surface molecules on CD4+CD25hign Tregs was detected by flow cytometry.The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro.Total serum immunoglobulin E (IgE) and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay,respectively.Results Equivalent numbers of peripheral Tregs were found in patients with atopic asthma (stable and acute) and healthy subjects.Tregs preferentially expressed CTLA-4, GITR,toll-like receptor 4 (TLR4),latency-associated peptide (LAP/TGF-β1),and forkhead box P3 (FOXP3).Patients with acute asthma had decreased numbers of CD4+CD25high LAP+ T cells compared to healthy subjects and stable asthmatics.Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently.Furthermore,the percentages of Tregs expressing LAP were negatively correlated with total serum IgE levels and severity of asthma,but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma.Concluslons The results suggest that membrane-bound TGF-β1 is a potential candidate for predicting the severity of asthma,and may contribute to the sustained remission of asthma,Strategies targeting Tregs on their surface markers,especially TGF-β1,are promising for future therapy of asthma。

Abstract：Background Traumatic damage to fascial and muscular support structures during childbirth may be a major factor of the development of stress urinary incontinence (SUI) and pelvic organ prolapse (POP).The aim of this study was to prospectively investigate the role of different childbirth strategies on POP and SUI.Methods A total of 120 selected pregnant women were recruited and divided into two groups:vaginal delivery group (n=72)and selective cesarean delivery group(n=48).The women were questioned with SUI sheet and estimated with POP quantification (POP-Q) within 6-8 weeks after delivery.The correlations of SUI and results of POP-Q with the strategies of delivery were analyzed.ttest,X2 test,and the Mann-Witney test were used for statistical analysis.Results Among the 120 women,SUI was developed during 29-30 gestational weeks in 20 patients (16.6%),of whom 14 (70%) had symptoms of SUI till 6 weeks postpartum. Totally 20 (16.6%) women had SUI symptoms after delivery.The prevalence of postpartum SUI was positively correlated with the occurrence of SUI during 29-30 gestational weeks (P＜0.001).In the vaginal delivery group,100% of the women suffered form urinary prolapse 6 weeks postpartum,while 87.5% of those in the selective cesarean delivery group developed POP (P＜0.01). The percentages of the first-and second-degree urinary prolapse in the vaginal delivery group were 20.8% and 79.2% respectively,which were significantly different from those in the selective cesarean delivery group (64.6% and 22.9%;both P=0.000).Conclusions Pregnancy and delivery play an etiologic role in the development of SUI and POP. The onset of SUI during late pregnancy implies a significant risk of postpartum SUI symptoms.The prevalence of POP is significantly higher after vaginal delivery than after cesarean delivery。

Abstract：Background Methylmalonic aciduria (MMA )is the most frequent disease of organic aciduria in China.Various biochemical strategies are followed for the prenatal diagnosis of MMA.However,since fetuses affected by MMA have decreased excretion of methylmalonic acid,the difficulties of prenatal biochemical diagnosis are obvious.Gas chromatography mass spectrometry (GC/MS) and tandem mass spectrometry (ESI/MS/MS) have allowed us to identify the disease in affected fetuses.The aim of this study was to determine the value of analysis of organic acids and total homocysteine in amniotic fluid in prenatal diagnosis of MMA.Methods The clinical diagnoses and outcomes of nine probands with MMA and the prenatal diagnoses based on biochemical analysis of nine fetuses at risk for MMA were investigated.Amniotic fluid samples from pregnancies at risk for MMA and metabolically normal pregnancies were obtained at 16-24 weeks of gestation.Methylmalonic acid and methylcitric acid were measured by GC/MS,propionylcarnitine was analyzed by ESI/MS/MS,and total homocysteine was determined by fluorescence polarization immunoassay.Results In two pregnancies,high levels of methylmalonic acid,methylcitric acid,propionylcarnitine,and total homocysteine indicated combined MMA and homocysteinemia in the fetuses.One of the mothers continued pregnancy and received cobalamin supplement as prenatal treatment,and the other terminated her pregnancy.In one pregnancy,significantly elevated levels of methylmalonic acid,methylcitric acid,and propionylcarnitine,and normal level of total homocysteine was found indicating isolated MMA in the fetus;abortion was performed on this case.In the other six pregnancies,all the levels of the above mentioned metabolites were normal suggesting that the fetuses were not affected by MMA. The diagnoses were confirmed after delivery by testing urinary organic acids and plasma total homocysteine.Conclusions The metabolic abnormalities of MMA occur early in gestation.The level of total homocysteine in amniotic fluid may be an additional indicator of fetal combined MMA and homocysteinemia.Determination of total homocysteine level in amniotic fluid may become a convenient and reliable method for prenatal diagnosis of the disease。

Abstract：Background Patients with systemic lupus erythematosus often have various autoantibodies.The relationship between these antibodies is still poorly understood.The aim of the present study was to observe the anti-SSB antibody and anti-dsDNA antibody production profiles following immunization with synthetic SSB peptide alone,DNA alone or co-immunization with these two antigens.Methods SSB 214-225 aa peptide was synthesized by organic chemistry solid-phase peptide synthesis.Rabbits were immunized with the foliowing antigens:synthetic SSB peptide linked with keyhole limpet hemocyanin (KLH),DNA,SSB plus dsDNA,KLH and PBS.Antibodies were measured by ELISA.Histopathology and direct immufluorescence assays were also applied.Results Ainit-SSB and anti-dsDNA antibodies were produced following immunization with SSB peptide and DNA respectively.The level of SSB antibody in the co-immunization group was higher than that of the SSB peptide immunization group.The level of anti-dsDNA antibody in the co-immunization group was,however,lower than that in the DNA immunization group.Meanwhile,the level of anti-SSB antibody was higher than that of anti-DNA antibody in the co-immunization group.No morphological or immunological abnormalities were found in the heart,liver,kidney,spleen or skin tissues.Conclusion Inhibition of anti-dsDNA-antibody was induced by co-immunization with synthesized SSB peptide and DNA,which might explain,at least partly,the mild disease in some LE subsets associated with SSB antibody。

Abstract：Background Astragali Radix,the root of Aatragalus membranceus(Fish)Bunge Var.mongholicus(Bge),is a crude drug considered as one of the effective traditional Chinese anti-ageing material.The two isomers of 4-hydroxy-5-hydroxymethyl-[1,3]dioxolan-2,6'-spirane-5',6',7',8'-tetrahydro-indolizine-3,-carbaldehyde(HDTIC),HDTIC-1 and HDTIC-2.were first extracted from the herb in 2002.We demonstrated previously that 0.1 μmol/L HDTIC-1 or 1.0 μmol/L HDTIC-2 strongly delay replicative senescence of human fetal lung diploid fibroblasts(2BS).In this study,we chose them to investigate their effects on the expression of senescence-associated genes to explore the mechanism of how HDTIC delays replicative senescence.Methods The effects of HDTIC-1 and HDTIC.2 on the expression of p16 and p21 were observed in vitro by RT-PCR and Western blot.The anti-oxidative activities of the compounds were also observed by phenotype alteration after treatment with antioxidants.Results There was an obvious expression of p16 in the control senescent cells.However,in the 2BS cells,after 56 population doublings(PDs)grown from PD28 in 0.1 μmol/L HDTIC-1 or 1.0 μmol/L HDTIC-2,there was a weak mRNA expression of p16 and no protein expression of p16 was observed.The expression level of p21 increased with cell ageing.Moreover.there was no difference between the expression leveI of p21 in the control cells and that in the same PD cells cultured with HDTIC compounds.The results also showed that 2BS cells exposed to 100 μmol/L H2O2 for 5 minutes return to their non-senescent phenotype and continue to be confluent after incubating the damaged cells with HDTIC-1 (1.0 μmol/L)or HDTIC-2(10 μmol/L)for 1 hour.Conclusions Expression of p16 by 2BS cells was strongly Inhibited by HDTIC compounds,which could contribute to their delayed replicative senescence by the way of p16INK4a/Rb/MAPK.The anti-oxidative activities of HDTIC-1 and HDTIC-2,described in this study for the first time,might be indirectly related to their inhibition of p16 expression。

Abstract：Background Angiotensin Ⅱ(Angll) and platelet-derived growth factor(PDGF)-BB can induce hypertrophy in the cultured rat cardiomyocytes through different signal transduction pathways.Angll stimulates growth lhrough G protein coupled receptor(GPCR),while PDGF-BB acts via receptor tyrosine kinase(RTK).Although there has been much development On the individual Angll and PDGF-BB mediated signal pathways,little is known about the interactions between these two factors-Therefore,the crosstalk between Angll and PDGF.BB mediated signal pathways in the rat cardiomyocytes was investigated in this study.Metnods Primary culture of neonatal rat ventricular myocytes was prepared.The amount of tyrosine-phosDhorylated and non-phosphoryiated PDGF-β receptor,Gαq/11,and phospholipase C(PLC)β3 were measured by immunoblotting analysis. The statistical analysis was done by one-way ANOVA.Results Fyrosine-phosphorylated PDGF-β receptor was increased by 120.60% at 1 minute and recovered to the control level at 10 minutes after Angll stimulation.Phosphorylation of PDGF-β receptor triggered by Angll was blocked by losartan, a specific antagonist of AT1 receptor.PLC inhibitor U73122,protein kinase C(PKC)inhibitor staurosporine(STS) and mitogen-activated ERK activating kinase(MEK) inhibitor PD98059 also inhibited the Angll-induced phosphorylation of PDGF-β receptor.PDGF-BB slightly increased the expression of Gαq/11 protein.Conclusion Angll transactivates PDGF-β receptor via AT1 receptor-Gαq/11-PLC-PKC pathway in the rat cardiomyocytes.ERK also participates in the transactivation of PDGF-β receptor triggered by Angll。

Abstract：Background Under an insulin resistance(IR)state,overproduction of reactive oxygen species(ROS)may be playing a maior role in the pathogenesis of endothelial dysfunction,hypertension and atherosclerosis.Recently,increasing attention has been drawn to the beneficial effects of heme oxygenase-1(HO-1)in the cardiovascular system.This study aimed to investigate the effects of HO-1 on vascular function of thoracic aorta in IR rats and demonstrate the probable mechanisms of HO-1 against endothelial dysfunction in IR states.Methods Sprague-Dawley (SD) rats fed with high-fat diet for 6 weeks and the IR models were validated with hyperinsulinemic-euglycemic clamp test.Then the IR rat models (n=44) were further randomized into 3 subgroups,namely,the IR control group (n=26, in which 12 were sacrificed immediately and evaluated for all study measures),a hemin treated IR group (n=10) and a zinc protoporphyrin-Ⅸ (ZnPP-Ⅸ)treated IR group (n=8) that were fed with a high-fat diet.Rats with standardized chow diet were used as the normal control group (n=12). The rats in IR control group,hemin treated IR group and ZnPP-Ⅸ treated IR group were subsequently treated every other day with an intraperitoneal injection of normal saline,hemin (inducer of HO-1,30 μmol/kg) or ZnPP-Ⅸ (inhibitor of HO-1,10 μmol/kg) for 4 weeks.Rats in the normal control group remained on a standardized chow diet and were treated with intraperitoneal injections of normal saline every other day for 4 weeks.Systolic arterial blood pressure (SABP) was measured by tall-cuffed microphotoelectric plethysmography.The blood carbon monoxide (CO) was measured by blood gas analysis. The levels of nitric oxide (NO),inducible nitric oxide synthase (INOS),endothelial nitric oxide synthase (eNOS),blood glucose (BG),insulin,total cholesterol (TC) and triglyceride (TG) in serum,and the levels of total antioxidant capacity (rAOC),maIondialdehyde (MDA) and superoxide dismutase (SOD) in the aorta were measured.The expression of HO-1 mRNA and HO-1 protein in aortal tissue were detected by semi-quantitative RT-PCR and Western blot. The vasoreactive tensometry was performed with thoracic aortic rings (TARs).Results Compared with the normal control group,the levels of SABP,BG,insulin,TC,TG,NO,iNOS and MDA were higher.while the levels of CO,TAOC,SOD and eNOS were lower in IR control rats.After treatment of IR rats for 4 weeks a more intensive expression of HO-1 mRNA and HO-1 protein were observed in hemin treated IR group compared with the normal control group.And compared with 4-week IR control rats,the levels of CO,TAOC,SOD and eNOS were increased,while the levels of SABP and iNOS activity were lower in the hemin treated IR group.Administration of hemin in IR rats appeared to improve the disordered vasorelaxation of TARs to acetylcholine (ACh).Alternatively,the reverse results of SABP,CO,TAOC,SOD,iNOS and vasorelaxation responses to ACh were observed in IR rats with administration of ZnPP-Ⅸ.Conclusions The endothelial dysfunction in the aorta is present in the IR state.The protective effects of HO-1 against aortic endothelial dysfunction may be due to its antioxidation and regulative effect of vasoactive substances.It is proposed that hemin,inducer of HO-1,could be a potential therapeutic option for vascular dysfunction in IR states。

Abstract：Background Hepatitis B virus (HBV) replication has been reported to be involved in many extrahepatic viral disorders;however,the mechanism by which HBV is transinfected into extrahepatic tissues such as myocardium and causes HBV associated myocarditis remains largely unknown.Methods In this study,endothelial progenitor cells (EPCs) were infected by HBV and then transfused into ischemic model of mice.HBV surface and core antigen as well as mutation of HBV particles were detected by immunonistochemistry,fluorescent activated cell sorter and transmission electron microscopy in vitro and in vivo.Results Human cord blood EPCs, but not human umbilical vein endothelial cells (HUVECs) could be effectively infected by taking up HBV in vitro.HBV envelope surface and core antigen expressions were first detectable in EPCs at day 3 after virus challenge,sustained for up to 11 days,and decreased thereafter.Similarly,the virus particles were the most abundant in EPCs ln the first week observed by a transmission electron microscope,and declined in 3 weeks after HBV infection.HBV DNA but not HBV cccDNA in EPCs were detectable even 3 weeks after virus challenge,as shown by PCR analysis.Furthermore,intravenous transplantation of HBV-treated EPCs into myocardial infarction Sprague & Dawley rats model resulted in incorporation of both EPCs and HBV into injured endothelial tissues of capillaries in the ischemic border zone.Conclusions These results strongly support that EPCs serve as virus carrier mediating HBV trans-infection into the injured myocardial tissues.The findings might suggest a novel mechanism for HBV-associated myocarditis。

Abstract：Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis,postangioplasty restenosis and transplant arteriopathy.Recently,pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis.But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not Vet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene (LDL-/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL-/-mice with the GFP-expressing transgenic mice. LDL-/- mice (22-24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice.Four weeks later,a nonconstrictive cuff was Dlaced around the right femoral artery.After another 2 weeks,both right and left femoral arteries were harvested and subjected to histochemical analysis.Apoptosis was analyzed in situ using TUNEL assay.Resuits Two weeks after cuff placement,atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells, The tissue stained with anti-α smooth muscle actin (SMA) antibody,showed a number of SMA-positive cells in the intimal lesion area.They were also positive for GFP,indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions.Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP.The intima and media showed a larae number of TUNEL-positive signals after 2 weeks cuff injury,indicating the presence of apoptosis in vascular remodelina.Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular inJury under the hypercholesterolemic conditions.Our data also clearly indicate that bone marrow-derived cells differentiated to smooth muscles and endothelial cells in the formation of these lesions in the presence of hypercholesterolemia。

Cells are endowed with a defensive mechanism against hypoxia,namely hypoxia-inducible factor (HIF) and hypoxia-responsive element (HRE).Under hypoxic conditions,activation of HIF leads to expression of a variety of adaptive genes with HRE in a coordinated manner。

Dendritic ceils(DCs)play a critical role in initiating the immune response by virtue of their ability to capture and present antigens to T cells.1 Although the precise mechanism by which DCs acquire human immunodeficiency virus (HIV-1) is not completely understood,migration of DCs from the periphery to the draining lymph nodes may enable CD4+ T cells to become infected.2

Ischaemic reperfusion injury (IRI) is a crucial element in the pathogenesis of acute ischaemic renal failure and influences the early functional recovery and even long term survival of a transplanted kidneyIt is generally thought that renal repair following IRI requires the replacement or regeneration of renal tubular epithelial cells that are detached or damaged。

The introduction of the antibiotics into clinical practice has significantly reduced the mortality of infectious diseases.Although chromosomally mediated β-lactamase is natural in many genera of bacteria.the intensive use of antibiotics is the main cause for the increasing emeNence of new β-lactamases.So far,more than 340 β-lactamases have been identified,1 among which,more than 200 are extended-spectrum β-lactamases (ESBLs).3 The most prevalent β-lactamases are class A enzymes,including SHV and TEM.Genes encoding these enzymes generally located in large transferable plasmids。

Because of the small diameter and complex anatomic course of the cranial nerves except for the optic nerve,mgeminal nerve,facial nerve,and cochlear and vestibular nerve,other cranial nerves are difficult to be visualized in magnetic resonance imaging (MRI) scanning with conventional thickness (5-10 mm)。

Non-Hodgkin's lymphoma (NHL) affects thoracic structures,particularly mediastinum and lung parenchyma,in up to 43% of patients at some stage in the course of the disease.1 Endobronchial involvement,however,is extremely rare,even in the presence of advanced disease。

Anaplastic large cell lymphoma (ALCL),a type of lymphoma,was first described by Stain in 1985 and included in non-Hodgkin lymphoma according to REAL classification since 1998.In the absence of necrosis,neutrophils infiltration in non-Hodgkin lymphoma is uncommon.Mann et all had previously reported neutrophil rich ALCL as a variant of ALCL.In this paper,we describe a neutrophil rich,anaplastic large cell lymphoma (ALCL) which presented as cutaneous nodules in an adolescent。

Cryptococcus neoformans (C. neoformans) is the most common cause of fungal meningitis worldwide.1 Cryptococcal meningitis is an opportunistic infection commonly found in immunocompromised hosts,especially HIV-infected adults. It also occurs in apparently immunocompetent individuals。