2008年·第121卷第07期

The development of the inflammatory processes in the pleural space may result in increased pleural vascular permeability leading to the accumulation of fluid enriched in proteins and the recruitment of cells into the pleural space.1

Abstract：Background The socio-economic burden of acute exacerbation of chronic obstructive pulmonary disease(AECoPD)in Beijing is not fully understood.The study investigated the hospitalization cost in patients with AECOPD and the associated factors.Methods A multi-center,retrospective study was conducted jn the four hospitals in Beijing including two level Ⅲ hospitals and two level Ⅱ hospitals.Patients with AECOPD admixed to the hospitals between January and December in 2006 were enrolled.The hosDitalization cost and its relationship with disease severity and treatment were analyzed.Results Totally 439 patients were enrolled with 294 men(67.0%)and a mean age 73.4 years.The mean hospital stay was 20.7 days.A total of 204 patients(46.5%)had respiratory failure,153(34.9%)with cor pulmonale,123(28.0%)with coronary artery disease,231(52.6%) with hypertension,70(15.9%)with cerebrovascuIar disease and 32(7.3%)with renal failure.The percentage of drug cost to total cost was the highest(71.2%),followed by laboratory cost(16.7%),therapy cost(9.7%),oxygen cost(7.3%),radiology cost(4.5%),examination cost(4.5%),bed cost(4.1%).Correlation analysis showed that cost was positively correlated with age,hospitalization days,co-morbidities such as respiratory failure and cor pulmonale,hypertension.Three hundred and twenty-one patients were further analyzed.The hospitalization cost increased in patients with non-invasive ventilation(P＜0.01),invasive mechanical ventilation(P＜0.01),ICU stay(P＜0.01),antibiotics(P＜0.05),systemic steroids(P＜0.01),and poor prognosis(P＜0.05).Correlation analysis showed that the hospitalization cost was negatively correlated with percentage forced expiratory volume in 1 second (FEV1%)(r=0.149,P＜0.05),Ph(r=-0.258,P＜0.01),and PaO2(r=-0.131,P＜0.05),positively correlated with PaCO2 (r=0.319,P＜0.01),non-invasive positive pressure ventilation(r=0.375,P＜0.01)and duration(r=0.463,P＜0.01),invasive mechanical ventilation(r=0.416,P＜0.01)and duration(r=0.511,P＜0.01),ICU stay(r=0.390,P＜0.01)and duration (r=0.650,P＜0.01),antibiotics(r=0.140,P＜0.05)and systemic steroids(r=0.202,P＜0.01).Conclusions AECOPD had a great impact on healthcare resources utilization.Disease severity,use of non-invasive or invasive ventilation,ICU stay and usage of antibiotics and systemic steroids were the major determinants of hospitalization cost.Long-term regular treatment aimed at reducing the frequency of acute exacerbation will lower the social and economic burden of chronic obstructive pulmonary disease (COPD)。

Abstract：Background Chronic obstructive pulmonary disease(COPD)and congestive heart failure(CHF)are two chronic diseases that affect negatively the functional condition and quality of life of patients.We assessed the effect of symptoms and clinical variables on the functional capacity and quality of life in COPD and CHF patients.Methods The study included 42 COPD and 39 CHF patients.In both patient groups,dyspnea was assessed using Borg scale;functional capacity by shuttle-walk and cardiopulmonary exercise test and quailty of life by short fOrm-36 (SF36).Results No statistically significant difference was found in neither of the two disease groups regarding the dyspnea score,shuttle-walk test and the maiority of subgroup scores of SF36 (P＞0.05).A statistically significant difference was obsewed in peak VO2 in favor of COPD group(P＜0.05).No significant relationship was established between dyspnea score and forced expiratory volume in one second(FEV1)in COPD patients,and left ventricular ejection fraction(L.VEF)in CHF patients (P＞0.05).A significant negative correlation was obsewed between dyspnea score and functional capacity tests in both disease groups(P＜0.05).On the other hand,no relationship was found between L-VEF and FEV1 and quailty of life and functional capacity (P＞0.05),Conclusions It was revealed that symptoms have an impact on functional capacity and quality of life in both disease groups,however,objective indicators of disease severity do not show a similar relationship.Therefore,in addition to the objective data related to the disease,we recommend that symptoms should also be taken into consideration to assess cardiopulmonary rehabilitation program and during following-up。

Abstract：Background Recent studies have revealed that lung cell apoptosis plays an important role in pathogenesis of cigarette-induced chronic obstructive pulmonary disease (COPD).Tumor necrosis factor alpha(TNF-α)is one of the most important cytokines which are involved in COPD.This study aimed at investigating the jnfluence of its inhibitor,recombinant human necrosis factor-alpha receptor Ⅱ:IgG Fc fusion protein(rhTNFR:Fc)on alveolar septal cell apoptosis in passive smoking rats.Methods Forty-eight rats were randomly divided into a normal control group,a passive smoking group,an rhTNFR:Fc intervention group and a sham intervention group.The passive smoking rats were treated by exposure to cigarette smoking daily for 80 days.Afcer smoking for one month the rhTNFR:Fc Intervention group was treated with rhTNFR:Fc by subcutaneous injection,the sham intervention group injected subcutaneousIv with a neutral preparation(normal saline 0.1 ml,manicol 0.8 ml,cane sugar 0.2 mg,Tris 0.024 mg as a control.Lung function was determined and the levels of TNF-α in serum and broncho-alveolar lavage fluid(BALF)were measured with enzyme-linked immunosorbnent assay (ELISA).Lung tissue sections stained by hematoxylin and eosin(HE)were observed for study of morphological alternations.Mean linear intercept(MLI)and mean alveolar numbers(MAN)were measured and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)method was carried out to determine the percentage of positive cells and distribution of apoptotic cells.Results Increased MLI and decreased MAN were found in the passive smoking group compared with both the normal control group and the rhTNFR:Fc intervention group(P＜0.05).Forced expiratory volume in 0.3 second(FEV0.3)/forced vital capacity(FVC)and peak expiratory flow(PEF)were lower in the passive smoking group than that in the normal control group(P＜0.05).Compared with the sham intervention group,FEV0.3/FVC and PEF increased in the rhTNFR:Fc intervention group (P＜0.05).The Ievels of TNF-α in serum were higher In the passive smoking group than that in the normal control group(P＜0.05)and rhTNFR:Fc intervention group(P＜0.05).Significant differences were found between the levels of TNF-α in the serum of the rhTNFR:Fc intervention group and sham Intervention group(P＜0.05).The levels of TNF-α in BALF were higher in the passive smoking group than that in the normal control group(P＜0.05),but no significant differences of TNF-α levels in BALF were found between the passive smoking group and rhTNFR:Fc intervention group.The number of TUNEL positive cells in alveolar septa was significantly increased in the passive smoking group as compared with the normal control group and the rhTNFR:Fc intervention group(P＜0.05).Conclusion This study provides preliminary evidence that rhTNFR:Fc may interfere with TNF-α and reduce alveolar septal apoptosis in smoking rats。

Abstract：Background Severe acute respiratory syndrome(SARS)is a disease with a mortality of 9.56%.Although SARS is etiologically linked to a new coronavirus(SARS-CoV)and functional cell receptor has been identified,the pathogenesis of the virus infection is largely unclear.Methods The clinical specimens were processed and analyzed using an indirect enzyme-linked immunosorbent assay (ELISA) in-house.Further investigations of target antigen included reviews of phage display technique,rapid amplification of cDNA ends(RACE)technique,protein expression and purification,Western blotting validation,serological and immunohistochemical staining in postmortem tissue.Results A type of medium or low titer anti-lung tissue antibodies were found in the sera of SARS patients at the early stage of the disease.Human long interspersed nuclear element 1(LINE1)gene endonuclease(EN)domain protein was one of the target autoantigens and it was aberrantly expressed in the lung tissue of SARS patients.Anti-EN antibody was positive in the sera of 40.9% of SARS patients.Conclusions Human LINE1 endonuclease domain was identified as a putative target of SARS-associated autoantibodies,which were presented in the serum of SARS patients and may be involved in the pathogenesis of SARS。

Abstract：Background Eppin(epididymis protease inhibitor)appears to play an important role in primate fertility.However,the function of Eppin and its antibody in men and its relationship with men's infertility are poorly studied.To reveal the significance and possibility of detection of anti-Eppin antibody in clinical infertilty cases,we developed an Escherichia coli expression system for the expression of biologically actire human Eppin.Methods The human Eppin gene was cloned into PET-28a(+)vector after induction with 0.5 mmol/L isopropy-β-D-thiogalactoside(IPTG)at 26℃ for 4 hours,and the expressed fusion protein His6-Eppin was purified by Ni2+ affinity chromatography.Afterwards,six female 8-week-old Balb/c mice were immunized with purified His6-Eppin for three weeks.Their sera were collected and polyclonal antibodies against His6-Eppin were purified,all of which were further verified by Western-blot and immunofluorescence analysis.Results About 18.33 mg His6-Eppin was obtained from 1-L flask culture.The produced polyclonal antibodies against His6-Eppin recognized the Eppin protein both in human epididymis and in HEK293T cells by over-expression of the recombinant human Eppin.Conclusion The purified His6-Eppin protein has biological activity,which might be a candidate for clinical diagnosis of infertility and development of male immuno-contraceptive agents。

Abstract：Background Invasive fungal infections are an important cause of posttransplant mortality in solid-organ recipients.The current trend is that the incidence of invasive candidiasis decreases significantly and invasive aspergillosis occurs later in the liver posttransplant recipients.The understanding of epidemiology and its evolving trends in the particular locality is beneficial to prophylactic and empiric treatment for transplant recipients.Methods A retrospective analysis was made of recorded data on the epidemiology,risk factors,and mortality of jnvasive fungal infections in 352 liver transplant recipients.Results Forty-two(11.9%)patients suffered from Invasive fungal infection.Candida species infections(53.3%)were the most common,followed by Aspergillus species(40.0%).There were 21 patients with a superficial fungal infection.The median time to onset of first invasive fungal infection was 13 days,first invasive Candida infection 9 days,and first invasive Aspergillus infection 21 days.Fifteen deaths were related to invasive fungal infection,10 to Aspergillus infection,and 5 to Candida infection.Invasive Candida species infections were associated with encephalopathy(P=0.009)and postoperative bacterial infection(P=0.0003)as demonstrated by multivariate analysis.Three independent risk factors of invasive Aspergillus infection were posttransplant laparotomy(P=0.004),renal dysfunction(P=0.005)and hemodialysis (P=0.001).Conclusions The leading etiologic species of invasive fungal infections are Candida and Aspergillus,which frequently occur in the first posttransplant month.EncephalOpathy and postoperative bacterial infection predispose to invasive Candida infection.POsttransDlant laparotomy and poor perioperative clinical status contribute to invasive Aspergillus infection.More studies are needed to determine the effect of prophylactic antifungal therapy in high risk Patients。

Abstract：Background Blood oxygen level-dependent(BOLD)functional magnetic resonance imaging(fMRI)plays an important role in identifying functional cortical areas of the brain.especially In patients with gliomas.This study aimed to assess the value of fMRI in presurgical planning and functional outcome of patients with gliomas in the motor cortical areas.Methods Twenty-six patients with gliomas in the motor cortex were recruited in the study.Before operation.fMRI was performed in each patient to obtain the mapping of bilateral hands area on the primary sensorimotor cortex.This examination was performed on a 3.0T scanner with a bilateral hands movement paradigm.During microsurgery under awake anesthesia,the motor area was identified using direct electrical stimulation and compared with preoperative mapping.Finally the tumor was resected as much as possible with the motor cortex preserved in each patlent.Karnofsky performance status(KPS)was evaluated in all patients before and after operation.Results Twenty-three patients showed a successful fMRI mapping.Among them,19 were calssified to be grade Ⅲ;4,grade Ⅱ;3,grade Ⅰ.The operation time was about 7 hours in the 23 patients,8.5 hours in the other 3.The pre- and pOstODerative KPS score was 82.3±8.6 and 94.2±8.1,respectively.Conclusions Preoperative fMRI of the hand motor area shows a high consistency with intraoperative cortical electronic stimulation.Combined use of the two methods shows a maximum benefit in surgical treatment。

Abstract：Background Total mesorectal excision(TME)has increased the rate of sphincter-preservation(SP)for more patients with low-lying rectal cancer.Here,we analyze the change of sphincter preserving rates in lower rectal cancer and their related factors.Methods We reviewed retrospectively the medical records of 316 patients with lower rectal cancers,1 to 5 cm from the anorectal line,who had surgical resections from August 1994 to November 2005.The 12-year span was divided into 2 periods:period Ⅰ(August 1994-December 1998)and period Ⅱ(January 1999-November 2005),based on the date (January 1999)when standard total mesorectal excision(TME)was introduced.The patients were divided jnto two groups based on the operation:abdominoperineal resection(APR)or SP surgery.SP rates,leakage and other clinicopathological characteristics were compared between the two time periods and between the two different groups.Results The SP rate increased significantly over the 12 years,from 44.9% in period Ⅰ to 76.2% in period Ⅱ(P=0.000).The factors significantly influencing SP included the distance of the tumor from the anorectal line,gender,time period,circumference of intramural spread and histological differentiation (P＜0.05).Significant differences were detected between the two time periods in gender,blood transfusion volume and Dukes'stage(P＜0.05).The leakage rate was 2.7% in period Ⅰ and 1.3% in period Ⅱ (P＞0.05).Conclusions Over the 12-year period of the study the SP rate in rectal cancers 1-5 cm from the anorectal line has increased significantly while the blood transfusion volume has decreased due to the introduction of TME.However,TME had no effect on operating time and leakage rates。

Mucus hypersecretion is a distinguishing feature of Chronic intlammation diseases,such as asthma,1chronic bronchitis.2 bronchiectasis3 and cystic fibrosis.4Mucus hypersecretion leads to impairment of mucociliary clearance,abnormal bacterial plantation,mucus plug in the airway,and dysfunction of gas exchange.5

Abstract：Background Active suppression by CD4+CD25+ regulatory T lymphocytes plays an important role in the down-regulation of T cell responses to foreign and self-antigens.This study was conducted to analyze whether the CD4+CD25+ regulatory T cells exist and function normally in tuberculous pleural effusion.Methods The percentages of CD4+CD25+ T cells in pleural effusion and peripheral blood from patients with tuberculous pleurisy and peripheral blood from healthy control subjects were determined by flow cytometry.The expression of forkhead transcription factor Foxp3 was also examined.CD4+CD25+ and CD4+CD25- T cells from pleural effusion and blood were isolated,and were cultured to observe the effects Of CD4+CD25+ T cells on proliferation response of CD4+CD25- T cells in Vitro.Results There were increased numbers of CD4+CD25+ T cells in tuberculous pleural effusion compared with peripheral blood from both patients with tuberculous pleurisy and normal subjects,and these cells demonstrated a constitutive high-level expression of Foxp3.Moreover,CD4+CD25+ T cells mediated potent inhibition of proliferation response of CD4+CD25- T cells.Conclusion The increased CD4+CD25+ T cells in tuberculous pleu ral effusion express a high level of Foxp3 transcription factor,while potently suppressing the proliferation of CD4+CD25- T cells。

Abstract：Background Lumiracoxib is a highly selective cyclooxygenase-2(COX-2)inhibitor with antiinflammatory,analgesic and antipyretic activities comparable with class specific drugs,but with much improved gastrointestinal safety.No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Drug-drug interactions were analyzed using the coefficient of drug interaction(CDI)to characterize the interactions as synergism,additivity or antagonism.Morphological changes were observed by acridine orange fluorescent staining.Extent of apoptosis was determined by flow cytometry.Results Lumiracoxib(15-240 μmol/L)has an inhibitory effect on the proliferation of A549 and NCI-H460 celllines in concentration- and time-dependent manners with the IC50 values of 2597 μmol/L and 833 pmol/L,respectively.The synergistic effect was prominent when lumiracoxib(15-240 μmol/L)was combined with docetaxol(0.2-2 μmol/L)(CDI ＜1).Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells.Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol,which may be related to apoptotic induction and cell cycle arrest。

Abstract：Background A novel anti-rheumatic drug,T-614,has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis(RA).To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients.Methods In a multicenter,randomized,double blind,placebo controlled study,280 patients were randomly assigned to receive placebo(n=95)or T-614 at 50 mg(n=93)or 25 mg(n=92)daily.Active disease was defined by 4 of the following 5 criteria:≥5 tender joints,≥3 swollen joints,morning stiffness lasting for≥60 minutes,and Westergren erythrocyte sedimentation rate(ESR)≥28 mm/h,the assessment of pain at the rest by patient as moderate or severe.Clinical and laboratory parameters were analyzed at baseline,2,4,6,12,18 and 24 weeks.The primary efficacy variable at week 24 was the American College of Rheumatology(ACR)response rate using the intent-to-treat population.Results The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment.After 24 weeks,the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%,61.29% and 24-21% in ACR20 and 23.91%,31.18%and 7.37% in ACR50,respectively.A time-response in ACR response was observed,with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo(P＜0.0001),and the 50 mg/d dose compared to the 25 mg/d dose(P＜0.05)when using the ACR response analyses after 24 weeks.ESR and c-reactive protein(CRP)were significantly different in the treatment groups after 24 weeks.The incidence of adverse events(Aes)was not significantly higher with T-614 than with placebo,but upper abdominal discomfort,leucopenia,elevated serum alanine aminotransferase(sALT),skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups.Conclusion T-614,a new slow-acting drug,is effective in treatment of rheumatoid arthritis and is well tolerated。

Asthma's prevalence and mortality have been increasing worldwide.Despite these increases significant advances have been made in the understanding of the immuno-modulatory mechanism of the disease。

Cytokeratin-positive interstitial reticulum cells(CIRCs)are considered to represent a subset of fibroblastic reticulum cells(FBRCs)belonging to accessory dendritic cells in lymph nodes,the spleen and tonsils.1-3

Neisseria meningitidis is the leading cause of bacterial meningitis and classified into 13 serogroups based on the immunological reactivity of the capsular polysaccharide.1 Serogroups A,B,C,W135 and Y are the most common causes of meningitis.2