2008年·第121卷第05期

Abstract：Background Neoadjuvant chemotherapy provides an excellent model for evaluation of potential predictive factors.The objective of this study was to evaluate the predictive value of different biological factors in breast cancer patients treated with neoadjuvant taxane and anthracycline chemotherapy.Methods One hundred and thirty-five patients treated with 4 cycles of neoadjuvant taxanes and anthracycline were included in this retrospective study.Using pretreatment biopsy materials,immunohistochemical studies were performed for estrogen receptor(ER),progesterone receptor(PgR),HER-2,Ki-67 and p53 protein expression.The associations among biological markers and clinical and pathological complete response (pCR)were analyzed.Results The overall clinical response was 86%,including 33%clinical complete response(cCR)and 53%clinical partial response.The pCR was iust 17%.In the univariate analysis,only HER-2 overexpression was predictive of cCR to neoadjuvant chemotherapy(P=0.018).No significant associations between other biological factors and cCR were found.Absence of ER,PgR expression and overexpression of HER-2 were predictive of the pCR(P=0.002,0.001,0.01,respectively).Ki-67 and p53 failed to show an association with pCR.In multivariate analysis,overexpression of HER-2remained as an independent variable in predicting the cCR(P=0.021).However,negative ER was the only parameter that maintained statistical significance in predicting the pCR(P=0.001).Conclusions Patients with overexoression of HER-2 and negative hormonal receptor status are much more likely to respond to neoadjuvant taxane and anthracycline chemotherapy than those with the opposite characte ristics.These factors could serve as predictive markers for this regimen。

Abstract：Background Growth and development of infants has been an impoRant topic in pediatrics for a long time.Infants must be provided with food containing all necessary nutrienls.Breast milk js believed to be the most desirable natural and cheapest food for well-balanced nutrition.But with the progress in the development of substitute food in developed countries,it is thought that formula milk can meet the requirement for infant growth.During early infancy,growth,as the most sensitive index of health,is therefore a critical component in evaluating the adequacy of breast-feeding,mixed-feeding and formula feeding.Iron status is another important index of infant health.Iron deficiency anemia remains the most prevalent nutritional deficiency index in infants worldwide.This study is to compare infants in Beijing at 4 months who are on three different feeding modes(breast feeding,mixed feeding and formula feeding)in physical changes and iron status.The results may provide new mothers with support in feeding mode selection,which will also be helpful to the China Nutrition Association in feeding mode education.Methods This is a cohort study.One thousand and one normal Beijing infants were followed regularly for 12 months.Body weight and horizontal length were measured.Hemoglobin,red blood cell counts,mean corpuscular volume,mean corpuscular hemoglobin and serum iron were analyzed at 4 months.Results The breast feeding percentage in the first 4 months was 47.9%.The feeding mode was not significantly related to maternal delivery age,education,labor pathway nor infant sex(P＞0.05).Infant boys and girls exclusively breast-fed from 0 to 4 months had the highest weight at 0-6 months.The anemia rate of breast-fed infant boys at 4 months was the highest.Conclusions Breast feeding should be given more emphasis.It is compulsory for new mothers to breast-feed their Infants if possible.Social environment should also guarantee the requirement for breast feeding.Furthermore the normal values of hemoglobin,mean corpuscular volume and serum iron,which were originally used to judge children's iron deficiency anemia,might not be optimal for evaluating infants.There might be a need to develop sex-specific cutoff levels of hemoglobin,mean corpuscular volume and serum iron for infants。

Abstract：Background Familial pulmonary arterial hypertension(FPAH)js an autosomal dominant disorder characterized by plexiform lesions of endothelial cells in pulmonary arterioles which leads to elevated pulmonary arterial pressure,right-sided heart failure and death.Heterozygous mutations in the bone morphogenetic protein type Ⅱ receptor gene (BMPR2)have been found to underlie a majoritv of FPAH cases.More than 140 distinct mutations have been identified in FPAH cases and in idiopathic pulmonary arteriaf hypertension(IPAH)cases,but only one mutation has been reported in Chinese patients.Methods A three-generation pedigree of FPAH and another 10 patients with IPAH were collected.In the family.two of the 9 surviving and one deceased family member were diagnosed as FPAH.The entire protein-coding region and intron/exon boundaries of the BMPR2 gene were amplified by PCR using DNA samples from affected individuals.Direct sequencing of PCR products was performed on both the sense and antisense strands.To confirm the segregation of the mutation within the family and exclude the presence of the mutation in normal subjects,the relevant exon was amplified by PCR,followed by mutation-specific RPLP analysjs.Results In the Chinese pedigree with FPAH an A-to-T transition at position 1157 in exon 9 of the BMPR2 gene was identified which resulted in a Glu386Val mucation.We confirmed the segregation of the mutation within the family and excluded the presence of the mutation in a panel of 200 chromosomes from normal subjects.No mutation was detected in BMPR2 in the other 10 patients with IPAH.Conclusions This amino acid substitution occurs at a glutamic acid that is highly conserved in all type Ⅱ TGF-βreceptors.The nearly invariant Glu forms an ion pair with an invariant Arg at position 491 thereby helping to stabilize the large Iobe.Substitution of Arg at position 491 is the most frequently observed missense mutation in FPAH,but until now no mutations at position 386 have been found in FPAH.The predicted functional impact of the Glu386Val mutation and its absence in healthy controls support the mutation as the cause of FPAH。

Abstract：Background Muscle fibers overlying the intramyocardiaI segment of an epicardial coronary artery are termed myocardial bridging(MB).Variable prevalence of MB has been described at autopsy and angiographic series with small and large sample size studies.In addition.no similar study was reported in Chinese population.The aim of this study was to investigate the angiographic prevalence of MB in consecutive 37 106 Chinese patients with chest pain from our center.Methods We conducted an observational study to evaluate the consecutive cases with MB among patients undergone selective coronary angiography,and analyzed the angiograhic prevalence and clinical features of MB in this study of very large sample size.Results Among 37 105 patients with chest pain we found 1002 cases with 1011 MBs in a retrospective manner,and the overall prevalence was 2.70%.Althouqh more than 99%(991/1002)of patients had single bridge,8 cases were found to have more than two MBs(seven with two,and one with three).Altogether 54.39% of cases(545/1002)had MB without atherosclerotic lesions,and 96.24%(973/1011)of bridging located in the left anterior descending coronary artery(LAD),mainly in the middle of LAD(792/1011,78.33%).According to Nobel classification,of the single bridge(n=991),＜50% of obstruction was predominant(471/991,47.52%).Tbtally 50%-69%accounted for 34.81%(345/991),＞70% of obstruction was 17.65%(175/991).Conclusions These data showed that the prevalence of angiographically detectable MB in Chinese patients with chest pain was similar to those of the previous studies,with 2.7% prevalence in this very large sample size。

Abstract：Background QacA,a main exporter mediating the multidrug-resistance of Staphylococcus aureus to a variety of to determine the importance and topology of amino acid residues in and flanking the cytoplasmic end of TMS5.Methods Site-directed mutagenesis was used to mutate 5 residues,including L146,A147,V148,W149 and S150,into cysteine.A minimum inhibitory concentration(MIC)and transport assay with or without N-ethylmaleimide(NEM)were performed to analyse the function of these mutants.Results All of the mutants showed comparable protein expression levels.MIC analysis suggested that mutant W149C showed low resistance levels to the drugs,but the mutations at L146,A147,V148,and S150C had little or no effect on the resistance level.And the results of the fluorimetric transport assay were in agreement with those of MIC analysis,that is to say,W149C did not allow transport to the substrates to be tested,while the other mutants retained significant transport ability.The reaction of the different mutant proteins with Fluorescein-NEM revealed that the mutant L146C was highly reactiMe with NEM:the W149C and S150C mutants were moderately reactive;A147C was barely reactive and V148C showed no reactivity.Conclusions The study identified that residues W149 and S150 situated at the intefface of the aqueous:lipid junction as functionally important residues,probably involved ln the substrate binding and translocation of QacA。

Abstract：Background The mechanism of cerebral vasospasm following subarachnoid haemorrhage(SAH)is not understood.Here,we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis(PUMA)played an important role in development of cerebral vasospasm.We also observed the effects of a p53 inhibitor,pifithrin-α(PFT-α),on reducing the expression of p53 and PUMA,consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm.Methods Male Sprague-Dawley rats weighing 300-350 g were randomly divided into five groups:a control group (sham surgery),a SAH group,a SAH+dimethyl sulfoxide(DMSO)group,a SAH+PFT-α(0.2 mg/kg)group and a SAH+PFr-α(2.0 mg/kg)group.PFT-α was injected intraperitoneally immediately after SAH.Rats were sacrificed 24hours after SAH.Western blot and immunohistochemical staining were used to detect the levels of p53,PUMA and caspase-3 protein.In addition,mortality and neurological scores were assessed for each group.Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test.The neurological and mortality scores were analyzed by Dunn's method and Fisher exact test,respectively.Results After SAH,Western blot and immunohistochemical staining showed the levels of p53,PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling(TUNEL)positive endothelial cells were all significantly increased in the basilar arteries (P＜0.05),but significantly reduced by PFT-α(P＜0.05).These changes were accompanied by increasing diameters and declining wall thickness of basilar arteries(P＜0.05),as well as reduced mortality and neurological deficits of the rats(P＜0.05).Conclusions PFT-α could protect cerebral vessels from development of vasospasm and improve neurological outcome as well as reduce the mortality via suppressing apoptosis induced by p53 in the endothelial cells of cerebral vessels。

Abstract：Background The balance between vasodilation and vasoconstriction plays a maior role ln maintaining vascular homeostasis.However,the underlying mechanisms are unclear.More and more evidence suggested that there was an interaction in the regulation of vasorelaxation between nitric oxide(NO)and hydrogen sulfide(H2S).We explored the interaction between and effects of NO and H2S on the relaxation of pulmonaw arteries in rats.Methods Seven male Sprague-Dawley rats were anaesthetized with chloral hydrate and the pulmonary arteries of each rat separated for the study of vascular activities.The vasorelaxing activities of pulmonary artery rings in response to different doses of a NO donor,sodium nitroprusside(SNP),or a H2S donor,sodium hydrogensulfide(NaHS),were measured in vitro.When pulmonary artery rings were treated with a cystathionine-y-lyase inhibitor,DL-propargylglycine,in the presence of SNP or a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester,in the presence of NaHS,the changes in relaxing activities were analyzed.Results The relaxation of pulmonary artery rings was in a dose dependent manner in response to either SNP or NaHS.The relaxation rates of pulmonaw artery rings increased from(30.90±4.62)%10(60.50±8.08)%when the concentration of SNP increased from 1 μmol/L to 3 μmol/L and from(26.13±4.12)%to(53.09±14.01)%when the concentration of NaHS increased from 25 μmol/L to 100 μmol/L.However,when appropriate inhibitor was added.the relaxation responses to SNP and NaHS decreased.Conclusions The results suggested that similarly to NO,H2S acted as a vasorelaxant either independently of,or synerqistically with NO in the regulation of vasorelaxation.The interaction between NO and H2S played an important role in regulating relaxing activities of pulmonary arteries。

Abstract：Background Proliferation,cell migration and phenotypic modulation of airway smooth muscle cells(ASMCs)are important features of airway remodelling in asthma.The precise cellular and molecular mechanisms that regulate ASMCs proliferation,migration and phenotypic modulation in the lung remain unknown.Basic fibroblast growth factor(bFGF),a highly specific chemotactic and mitogenic factor for many cell types,appears to be involved in the development of airway remodelling.Our study assessed whether bFGF directly stimulates the proliferation,migration and phenotypic modulation of ASMCs.Methods Confluent and growth arrested human ASMCs were treated with human recombinant FGF.Proliferation was measured by BrdU incorporation and cell counting.Migration was examined using Boyden chamber apparatus.Expressions of smooth muscle(sm)-α-actin and sm-myosin heavy chain(MHC)isoform 1 were determined by RT-PCR and Western blot analysis.Results It was found that hrbFGF(10 ng/ml),when added to ASMCs,induced a significant increase in BrdU uptake and cell number by ASMCS as compared to controls and a significant increase in ASMCs migration with respect to controls.The mRNA and protein expressions of sm-α-actin and sm-MHC in ASMCs that were stimulated with hrbFGF decreased with respect to controls.Conclusion It appears that bFGF can directly stimulate proliferation and migration of ASMCs.however,the expressions of cells'contractive phenotype decreased。

Abstract：Background Hereditary spastic paraplegia(HSP)is a group of inherited neurodegenerative disorders with the shared characteristics of slowly progressive spasticity and weakness of the lower limbs.Thirteen loci for autosomal dominant HSP have been mapped.Methods A Chinese family with HSP was found in the Shandong province and Inner Mongolia Autonomous Region of China and genomic DNA of all 19 family members was isolated.After exclusion of known autosomal dominant loci,a genome wide scan and linkage analysis were performed.Results The known autosomal dominant loci of SPG3A,SPG4,SPG6,SPG8,SPG9,SPG10,SPGl2,SPG13,SPG17,SPG19,SPG29,SPG31 and SPG33 were excluded by linkage analysis.The results of a genome wide scan demonstrated candidate linkage to a locus on chromosome 11p14.1-p11.2,over an 18.88 cM interval between markers D11S1324 and D11S1933.A maximal,two point LOD score of 2.36 for marker D11S935 at a recombination fraction(Φ)of 0 and a multipoint LOD score of 2.36 for markers D11S1776,D11S1751,D11S1392,D11S4203,D11S935,D11S4083,and D11S4148at Φ=0,suggest linkage to this locus.Conclusion The HSP neuropathy in this family may represent a novel genetic entity,which will facilitate discovery of this causative gene。

Abstract：Backgroud Interleukin 1β(IL-1 β)is the principal mediator in the pathogenesis of rheumatoid arthdtis.Continuous injection of interleukin 1β(IL-1β)into the knee articular cavities of anamals can induce models that resemble rheumatoid arthritis.The obiective of this study was to evaluate the feasibility of local recombinant retrovirus viral intedeukin 10(rRV-vIL-10)gene transfer treatment of a rabbit model of arthritis induced by IL-1β.Methods An hIL-1β-induced rabbit rheumatoid arthdtis model was established using the MFG-hIL-1β-neo-HIG-82 cell line,which is capable of continuous secretion of hIL-1a.After transfecting the rabbit synovial fibroblast cell line (MFG-hIL-1β-neo-HIG-82)with rRV-vIL-10,G418 was then added to identify the positive clone.The rRV-vIL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection.Successful gene transfer was determined by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry.The levels of IL-1β before and after treatment were determined by enzyme-linked immunosorbent assay.Results Retrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry.The rabbit arthritis model treated with rRV-vIL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1β.Conclusions Retrovirus-mediated transfection of vIL-10 successfully transferred the gene into rabbit syrnovium ex vivo and was able to suppress intra-articular inflammation response to IL-1β。

Prognostic factors are biological or physical characteristics of a oatient or the Datient's cancer that can be used to predict the outcome of the individual.1,2

Vascular calcification is commonly found in atherosclerosis and recognized as a marker of atherosclerotic plaque burden.Many evdiences have demonstrated that vascular calcification is an active process and can be seen in all stages of development and intimately associated with atherosclerosis。

Coronarv artery fistula(CAF), an uncommon congenital heart disease,often results in myocardial ischemia.1-3 In the last two decades,there are some reports about interventional treatment of CAF,4-6but few on transcatheter treatment of multiple CAFS.With different interventional procedures, we treated successfully two cases of percutaneous closure of two multiple CAFs which were confluent at the distal ends.…… Biography：Dr. SHEN Xiang-qian,Department of Cardiology,Second Xiangya Hospital,Central South University,Changsha,Hunan 410011,Chirla(Tel:86-731-5292012.Email:xiangqian19982008@yahoo.com.cn)Correspondence to

Thymic carcinoma is a malignancy of the anterior mediastinum with a poor prognosis that is thought to be derived from thyrnic epithelium and they represent approximately 6% of primary mediastinal tumors.1Because of the lack of literature discussing the clinical and pathologic features and treatment Of this tumor,thymic carcinoma has been a somewhat controversial disease up to now。

To the Editor:As we know.Calculus Boris(Niuhuang in Chinese,the gallstone of Bos taurus domesticus Gmelin)is one of the most precious and commonly-used medicinal materials in China.1