2004年 · 第117卷第11期

Background Adiponectin, secreted by adipocytes, has been found to be associated with diabetes, obesity and some cardiovascular diseases. Obstructive sleep apnea hypopnea syndrome (OSAHS) is also closely related to obesity and easily complicated with diabetes and some cardiovascular diseases. This study was carried out to explore the change of serum adiponectin level inpatients with OSAHS. Methods Polysomnography was performed in 71 patients with OSAHS (OSAHS group) and 26 single obese controls (control group). The two groups had no significant difference in age and body mass index(BMI). Radioimmunoassy was used to test serum adiponectin level. Results Serum adiponectin level was significantly lower in OSAHS group [(5. 03 ± 1. 01) mg/L] than that in the control groip [(7.09 ± 1.29) mg/L, P <0. 05] . The differences between two groups were independent of gender. In OSAHS groups, serum adiponectin levels were negatively correlated with apnea hypopnea index (AHD (r= - 0.78, P <0. 01), BMI (r= - 0. 13, P <0. 05) ? waist circumsference (r= -0. 36, P <0.01), and neck circumference (r=- 0.42, P <0. 01), but positively correlated with the minimal pulse oxyhemoglobin saturation (r=0. 48, P <0. 01). Conclusion OSAHS may contribute to the decrease of serum adiponectin level independent of obesity. Chin Med J 2004; 117 (11): 1603-1606

Background Platinum-based chemotherapy has been proved effective in patients with advanced non-small cell lung cancer (NSCLC) . This study evaluated the effectiveness and safety of first-line chemotherapy with gemcitabine plus cisplatin (GEM-Cis) 3-week regimen in routine care of Chinese patients with advanced NSCLC. Methods Two hundred and twenty-one patients with NSCLC stage Ⅲb or Ⅳ were enrolled and 209 were eligible for effectiveness and safety analysis. The median age was 58 (range 29 to 79) years. The percents of cases in stage Ⅳ and stage Ⅲb were 52. 2 %and 47. 8 %; of Karnofsky performance score(KPS) less than 80 and 80 - 100 were 37. 3 %and 62.7 %and of adeno-cancer and non-adeno-cancer were 59. 8 %and 40.2 %. The average number of completed chemotherapy cycles was three. Measures of effectiveness included clinical benefit, significant clinical response (SCR) and adverse effects of GEM-Cis in the treatment of NSCLC at stages Ⅲb/ Ⅳ. Results KPS increased from 79 ± 9 at baseline to 86 ± 10 after chemotherapy (P <0. 01). Lung cancer symptom scale (LCSS) score of pain, dyspnea and cough increased from 77 ± 24, 74±22 and 63±19 to 92 ±15, 90 ±14 and 86 ±15, respectively (P <0.01) . The clinical benefit rate was 85. 2 %[95 %confidence interval (CI) 80. 3 %- 90. 0 %]. The SCR was 89. 5 %(95 %CI 85. 3 %- 93.7 %). Median survival time was 7.8 months (95 %CI 7. 1 months - 9. 1 months) . Sixty-four patients (30.6 %)experienced an adverse effect that was deemed clinically significant. Only one patient (0. 5 %) was hospitalized due to chemotherapy related adverse effects. Life-threatening toxicity was observed in two patients (1.0%). Conclusion First-line chemotherapy with GEM- Cis in the routine care of Chine se patients with advanced NSCLC is effective and safe. Chin Med J 2004; 117 (11): 1607-1610

Background T lynphocytes and matrix metalloproteinase (MMP) play an inportant role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the details of the mechanisms involved are unclear. The aims of this study were to investigate the changes in interferon-γ (IFN-γ),interleukin-4 (L-4), MMP-9, MMP-12 and tissue inhibitor of metalloproteinase-1 (TMP-1) levels in a smoke-induced COPD rat model and the therapeutic effects of glucocorticoids and N-acetylcysteine. Methods Male Wistar rats were exposed to cigarette smoke for 3.5 months. Budesonide or N-acetylcysteine was given in the last month. Lung function was measured at the end of the study. L-4 and IFN-γlevels were then determined in bronchoalveolar lavage fluid and lung tissue sanples by enzymelinked immunosorbent assay. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissue was determined by RT-PCR. Results In conparison with the control group, rats exposed to smoke had a significant increase in IL-4 and MMP-12 levels and a significant decrease in IFN-γ levels. In addition, the IL-4/ IFN-γratio and MMP-12/ TMP-1 ratio were both higher. At the same time, the ratio of forced expiratory volume in 0. 3 second to forced vital capacity (FEV0.3/FVC) and dynamic conpliance (Cdyn) decreased and expiratory re si stance(Re) increased. By measuring pulmonary mean linear intercept and mean alveolar numbers, obvious emphysematous changes were observed in the smoke exposed group. After treatment with budesonide, IL-4 and MMP-12 decreased and IFN-γincreased. The IL-4/IFN-γratio returned to normal, though the MMP-12/ TMP-1 ratio remained unchanged. FEV0.3/ FVC was significantly higher and Re was significantly lower than that in untreated smoke exposed rats. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. After treatment with N-acetylcysteine, IFN-γincreased and the IL-4/IFN-γratio decreased. The MMP-12/ TIMP-1 ratio remained unchanged. Re and Cdyn both improved obviously. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. Correlation analysis indicated that L-4 levels in lung tissue correlated negatively with FEVo.3/FVC (r= - 0. 53, P=0. 001), IFN-γ levels in lung tissue correlated negatively with Re (r= - 0. 63, P= 0. 000) and positively with Cdyn(r=0. 44, P=0. 009), and that the IL-4/ IFN-γratio correlated negatively with FEVo.3/ FVC (r= -0.44, P=0.010) and Cdyn(r= - 0.42, P=0.015) and positively with Re (r= 0.58, P=0. 000). Finally, MMP-12 correlated negatively with FEVo. 3/ FVC (r=- 0. 36, P=0. 026). Conclusions Cigarette smoke exposure increases the re suit of smoke-induced changes inlung function. γ levels induced by smoke exposure. N-acetylcysteine has no effect on IL-4, but increases IFN-γlevels and brings the IL-4/ IFN-γratio back to normal. Cigarette smoke can also promote MMP-12 gene egression and elevate the MMP-12/ TMP-1 ratio. This effect may play a role in smoke-induced emphysema. Budesonide and N-acetylcysteine do not alter the MMP-12/ TMP-1 L-4 levels and decreases IFN-γlevels. This may be Budesonide can mitigate the changes in IL-4 and IFN-ratio in this study when given in the late phase of smoke exposure. Chin Med J 2004; 117 (11): 1611-1619

Background There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. Methods Forty sensitized guinea pigs were randomly divided into four groups: control (n=10), challenge (n=10), SB207499 (n=10) and aminophylline (n=10), then challenged with aerosol of 1 %ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2. 5 mg/ kg and 25 mg/ kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150 % of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in broncho alveolar lavage fluid were analysed. Results The cough frequency per 3 minutes and PC150 in the challenge group were (22 ±4) times/ 3 minutes and (198 ±54) μg/ml, which were significantly different from (6 ±2) times/ 3 minutes and (691 ± 81) μg/ ml in the control group (P <0. 05, respectively). The injection of 25 mg/ kg SB207499 significantly inhibited the increased cough response and airway hyperre sponsiveness, the cough frequency and PC150 in guinea pigs were (13 ±2) times/ 3 minutes and (680 ±81) μg/ ml (P <0. 05), which differed significantly from (18 ±2) times/ 3 minutes and (400 ± 86) μg/ ml after the administration of the same dose of aminophylline (P <0. 05). The inhibition of SB207499 on cough response was dose-dependent. Similarly, SB207499 decreased the total cell number and percentage of eosinophils in broncho alveolar lavage fluid to(2. 1 ±0. 5) ×106/ ml and (20 ±5) % respectively, which were significantly different from (3.2 ±0.5) × 106/ ml and (29 ±5) %in the aminophylline group (P <0.05, respectively) or (4.2 ±0.7) X106/ ml and(35 ±4) %in the challenge group (P <0. 05, respectively). Conclusion Phosphodiesterase 4 inhibitor may be more useful than aminophylline for cough associated with eosinophilic airway inflammation via inhibiting airway inflammation and airway hyperre sponsiveness. Chin Med J 2004; 117 (11): 1620-1624

Background The etiologic agent of severe acute respiratory syndrome (SARS) has been confirmed to be a novel coronavirus (CoV), namely SARS-CoV. Developing safe and effective SARS-CoV vaccines is essential for us to prevent the possible reemergence of its epidemic. Previous experiences indicate that inactivated vaccine is conventional and more hopeful to be successfully developed. Immunogenicity evaluation of an experimental inactivated SARS- CoV vaccine in rabbits was conducted and reported in this paper. Methods The large-scale cultured SARS-CoV F69 strain was inactivated with 0. 4 % formaldehyde and purified, then used as the immunogen combined with Freund' s adjuvant. Eight adult New Zealand rabbits were immunized four times with this experimental inactivated vaccine. Twelve sets of rabbit serum were sampled from the third day to the seventy-fourth day after the first vaccination. The titers of specific anti-SARS-CoV IgG antibody were determined by indirect enzyme-linked immunosorbent assay, and the neutralizing antibody titers were detected with micro-cytopathic effect neutralization test. Results Rapid and potent humoral immune responses were induced by the inactivated SARS-CoV vaccine in all the eight test rabbits. liters of both specific IgG antibody and neutralizing antibody peaked at about six weeks after first vaccination, with the maximum value of 18:1 920 and 120 480, respectively. After that, serum antibody levels remained at a plateau or had a slight decrease, though two boosters were given in the succedent 4 to 5 weeks. Cross neutralization response existed between SARS-CoV F69 strain and Z2-Y3 strain. Conclusions The inactivated SARS-CoV vaccine made from F69 strain owns strong immunogenicity, and the cross neutralization response between the two different SARS-CoV strains gives a hint of the similar neutralizing epitopes, which provide stable bases for the development of inactivated SARS-CoV vaccines. Chin Med J 2004; 117 (11): 1625-1629

Background Potassium (K+) channels are inportant in regulating cell membrane potential and excitability. Although bronchial myocytes from asthmatic rats show a significant reduction in voltage-dependent delayed rectifier potassium channel (Kv) current density and higher excitability, the activity and expression of Kv in human bronchial smooth muscle cells (HBSMCs) have never been studied. The objective of this study was to investigate the effect of passive sensitization by asthmatic serum on the activity of Kv and the expression of Kv isoform Kvl. 5 in HBSMCs. Methods HBSMCs were randomly divided into two groups: control group (containing 10%serum from nonatopic individuals) and sensitized group (containing 10 %asthmatic serum), then cultured for 24 hours. Whole-cell patch clanp, immunofluorescence staining, reverse transcription-polymerase chain reaction and Western blot techniques were used to study the effect of passive sensitization on the activity of Kv and the expression of Kvl. 5 in HBSMCs. Results The membrane potential in passively sensitized HBSMCs was significantly depolarized to - (26. 7 ±5. 2) mV compared with -(41. 3 ±6. 4) mV in the control group (P <0. 01) . Passive sensitization caused a significant inhibition of Kv currents in HBSMCs, re suiting in a downward shift in the current-voltage (I - V) relationship curve. At + 50mV, the peak Kv current density of passively sensitized HBSMCs was significantly decreased from (54. 6 ± 8. 7) picoamperes per picofarad (pA/pF) to(32. 1 ±7. 1) pA/pF (P<0.01). The expression level of Kvl. 5 mRNA in passively sensitized HBSMCs was significantly lower than that in the control group (0. 76 ±0. 07 vs 1. 04 ±0. 13, P <0. 05) . The expression of Kvl. 5 protein of passively sensitized HBSMCs was also significantly reduced conpared to that from the control group (984 ±168 vs 2200 ±80, P<0. 05). Conclusions The activity and expression of Kv were all decreased in HBSMCs passively sensitized by asthmatic serum compared with nonsensitized cells. These changes might be involved in the mechanisms of formation and development of asthma. Chin Med J 2004; 117(11): 1630-1636

Background Inherited factors are involved in the development of chronic obstructive pulmonary disease(COPD). This study was de signed to investigate the relationship between polymorphisms of HDEFB1 668 C/ Gand 1654 G/ A loci and susceptibility to COPD in Chinese Han population. Methods After the process of extracting genomic DNA from peripheral blood of COPD smokers and healthy smokers, the loci of genotypes 668C/ G and 1654 G/A were determined by polymerase chain re action-re restriction fragment length polymorphism analysis and polymerase chain reaction- single strand conformation polymorphism analysis. Results With respect to HDEFB1 668 locus, the occurences of CC, CG, GG genotypes were 72.7 %, 25. 0 %, 2. 3 % in COPD smokers and 53. 2 %, 38. 3 %, 8. 5 % in healthy smokers (P <0. 05, respectively).The allele frequencies of 668 C and 668G were 85. 2 %and 14. 8 %in COPD smokers and 72. 3 %and 27. 7 %in healthy smokers (P <0. 01, respectively, odds ratio was 2. 32 with 95 %confidence interval 1.37 to 3.72) . As to HDEFB1 1654 G/ A locus, neither genotype distribution difference nor allele distribution difference was found when comparing COPD smokers with healthy smokers. Conclusion The polymorphism of HDEFB1 668C/ Gis associated with susceptibility to COPD in Chinese Han population; furthermore, the 668 G allele represents relatively lower susceptibility to COPD. Chin Med J 2004; 117 (11): 1637-1641

Background Expression of polo-like kinase 1 (Plkl) is elevated inlung cancer and has beenproposed as having prognostic value and related to re si stance to chemotherapy and radiation. In addition, Plkl has several functions in mitotic progression. In this study, the authors investigated the effect of Plkl depletion on cell cycle progression and proliferation in A549 cells, a lung cancer cell line. Methods A recombinant plasmid containing antisense RNA targeting Plkl (pcDNA3-Plkl) was transfected into A549 cells. Reverse transcriptio n-polymerase chain reaction and Western blot were used to examine Plkl gene expression. Cell proliferation was evaluated by direct cell counting and bromodeoxyuridine(BrdU) labelling. Cell cycle and apoptosis were examined by flow cytometry. Expression of α-tubulin was detected by immunofluorescence, and the inhibition rate (IR) by chemotherapeutic agents was determined by 3- (4,5-dimethylthiazo 1-2-yl) 2,5-diphenyl-tetrazolium bromide assay. Results After transfectioninto A549 cells, pcDNA3-Plkl reduced Plkl mRNA by 46. 75 % for 24 hours and by 61. 84 % for 48 hours. Plkl protein was significantly decreased simultaneously (P <0. 05). Abnormal morphological changes of cells and growth inhibition were observed in pcDNA3-Plkl transfected groups. The BrdU labelling index was 25. 59 %48 hours after transfection, which was significantly lower than that of the control groups (P <0. 05). Forty-eight hours after transfection, there showed absence of microtubule polymerization and spindle abnormalities in staining for α-tubulin. A549 cells showed a strong G2/M arrest and apopto sis 72 hours post transfection. IR of vinorelbine in pcDNA3-Plkl transfected groups was significantly higher than that of the other groups (P <0. 05, respectively). Conclusions Plkl depletion interferes with spindle formation, induces cell cycle arrest and apopto sis, and consequently inhibits cell proliferation in A549 cells. Moreover, it sensitizes lung cancer cells to chemotherapy. Chin Med J 2004; 117 (11): 1642-1649

Background Cardiovascular diseases, especially coronary artery disease (CAD), are major causes of death in industrialized countries. Elevated concentrations of plasma homocysteine (Hcy) have been associated with an increased risk of CAD. Increased plasma levels of chemokine, characterized by their ability to induce migration and activation of leukocytes, may contribute to the pathogenesis of CAD. This study was designed to investigate the changes of plasma Hcy, monocyte chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary syndrome patients. Methods A total of 149 subjects were divided into four groups: 50 patients with unstable angina, 30 patients with acute myocardial infarction, 20 coronary restenosis patients after percutaneous coronary intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1, malondialdehyde and superoxide dismutase were measured. Results Plasma levels of Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial infarction and restenosis patients compared with control subjects (P <0. 05, respectively). Plasma levels of malondialdetyde were significantly increased in unstable angina and acute myocardial irfarctionpatients when compared with control subjects (P <0.05, respectively) . Plasma superoxide dismutase levels were significantly reduced in acute myocardial irfarction patients when compared with control group (P <0. 01). Conclusion Hcy might act as an atherogenic factor through promoting chemokine, reactive oxigen species and oxidized low density lipoprotein production and thereby convert a stable plaque into an unstable potentially occlusive lesion. Chin Med J 2004; 117(11): 1650-1654

Background Isolated dextrocardia is a rare phenomenon and usually associated with multiple cardiac anomalies. This study was to evaluate the accuracy of diagnosis of isolated dextrocardia by using angiocardiography and to compare it with the re sults of surgery. Methods The clinical data of 27 cases of congenital isolated dextrocardia were collected to understand the diagnostic approaches to the major cardiac anomalies. All cases underwent angiocardiography followed by palliative or curative surgery. The diagnosis was compared by angiocardiography relying on segmental analysis with the pathological features observed in surgery. Results The results of angiocardiography of 22 patients were the same as the pathological features observed during surgery, including one case with congenital left ventricular diverticulum was inadvertently omitted in angiocardiograhy. There were significantly dissimilar diagnoses between angiocardiograhy and post-operation in 5 patients, including anatomical corrected transposition of great arteries misinterpreted as corrected transposition of the great arteries in 1, complete transposition of great arteries misinterpreted as corrected transposition of the great arteries in 1, single ventricle misinterpreted as double-outlet right ventricle in 1, and anatomical double-outlet left ventricle misinterpreted as corrected transposition of the great arteries in 2. Msdiagnostic rate of angio c ardio grahy was almost 20 %. Conclusions Angiocardiography is of great significance in the diagnosis and classification of isolated dextrocardia. However, because of the intricacy of cardiac anomalies of isolated dextrocardia, atrial angiography and double oblique projection are needed to improve the accuracy of diagnosis to support surgical treatments. Chin Med J 2004; 117 (11): 1655-1658