2003年 · 第116卷第09期

Objective To investigate the dynamic changes observed in serum levels of interleukins(ILs), tumor necrosis factor-a(TNF-α)and transforming growth factor-β1(TGF-β1)in severe acute respiratory syndrome(SARS)patients. Methods Sixty-one cases of SARS with positive antibodies to SARS coronavirus(SARS-CoV)were classified into the following categories: initial stage(3-7 days), peak stage(8-14 days), and remission and recovery stage(15-27 days). Forty-four healthy individuals were used as controls. Serum levels of ILs, TNF-α and TGF-β1 were measured in all subjects. Serum antibodies to SARS-CoV were detected only in SARS cases. Results The mean concentration of serum IL-6 in SARS patients did not differ from that in the control group in initial and peak stages, but became significantly higher in remission and recovery stage compared with the control group, initial and peak stages(P<0. 01). The mean concentration of serum IL-8 in SARS patients did not differ from that of the control group in initial stage, but was significantly higher than control group in peak stage and remission and recovery stage(P<0. 05). And it was more significantly higher in remission and recovery stage than in peak stage(P<0. 01). The mean concentrations of IL-16 and TNF-α in SARS patients were higher than those of the control group for every length of the clinical courses investigated, and were especially high in remission and recovery stage(P < 0. 01). SARS patients experienced higher concentration of serum IL-13 compared with the controls in initial stage(P<0. 01), but returned to normal levels in peak stage and in remission and recovery stage. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all clinical courses(P<0. 05). The mean concentration of serum TGF-β1 in SARS patients was higher than that of the control group during all clinical courses. Although TGF-β1 in serum decreased in remission and recovery stage in SARS patients, the average was still higher than that of the control group(P<0. 01). Conclusions Most proinflammatory cytokines and TGF-β1 were elevated during the early phase of SARS, which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually, and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during all the courses of SARS, suggesting that the immune state of the patients with SARS was obviously abnormal. Observing the dynamic changes in blood treatment of SARS.

Objective To study the severe acute respiratory syndrome(SARS)-associated coronavirus genotype and its characteristics. Methods A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29 715 bp(GenBank accession: AY297028, version: gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done. Results By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci(C:G:C:C/T T:T T)involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes(C:G:A:C:C/T:T:G:T: T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in mainland China. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two(A/G and C/T)of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to lle in the protein, respectively. Conclusion Attention should be paid to whether these genotype and mutation patterns are related to the virus ' s biological activities, epidemic characteristics and host clinical symptoms. Chin Med J 2003; 116(9): 1288-1292

Objective To identify valid measures for preventing outbreaks of severe acute respiratory syndrome(SARS)among protected healthcare workers in isolation units. Methods Architectural factors, admitted SARS cases and infection of healthcare workers in different isolation wards between January 30 and March 30, 2003 were analyzed. Results Four types of isolation wards were analyzed, including the ward where the thirty-first bed was located on the twelfth floor, the laminar flow ward in the Intensive Care Unit where the tenth bed was located on the fifteenth floor, the ward where the twenty-seventh bed was located on the thirteenth floor of the Lingnan Building, and thirty wards on the fourteenth to eighteenth floors of the Zhongshan Building. The ratios(m2/m3)of the area of the ventilation windows to the volume of the rooms were 0, 0, 1:95 and 1: 40, respectively. Numbers of SARS cases in the wards mentioned above were 1, 1, 1 and 96, respectively. Total times of hospitalization were 43, 168, 110 and 1272 hours, respectively. The infection rates of the healthcare workers in the areas mentioned above were 73. 2%, 32. 1 %, 27. 5% and 1.7%, respectively. The difference in the infection rates was of statistical significance. Conclusions Isolating SARS cases in wards with good ventilation could reduce the viral load of the ward and might be the key to preventing outbreaks of SARS among healthcare workers along with strict personal protection measures in isolation units. Chin Med J 2003;116(9): 1293-1297

Objectives To investigate patients with acute lymphoblastic leukemia(ALL)for TEL/AML1 fusion, BCR/ABL fusion, MLL gene rearrangements, and numerical changes of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization(FISH)and to determine the relationship and the significance of those findings. Methods Fifty-one American patients(34 men and 17 women)were included in this study. Of them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 1 with T cell type ALL. Chromosome metaphases of each sample were prepared according to standard protocols. Fluorescence in situ hybridization was performed using commercially available DNA probes, including whole chromosome painting probes, locus specific probes, specific chromosome centromere probes and dual color/multiple color translocation fusion probes. The digital image analysis was carried out using Cytovision and Quips FISH programs. Results An overall incidence of chromosomal anomalies, including t(9;22), MLL gene rearrangements, t(12; 21), and numerical chromosomal anomalies of chromosomes 4, 10, 17 and 21 was found in 33 patients(65%). Thirty-one of them were pediatric patients and two adults. The t(12; 21)was the commonest chromosomal anomaly detected in this population; 14 out of the 45 pediatric patients(31 %)were positive for TEL/AML1 fusion, among which three had an additional derivative 21 [t(12;21)], four had a deletion of 12p and two had an extra copy of chromosome 21. All 14 patients with positive TEL/AML1 fusion had ALL pre-B cell or B-cell lineage according to standard immunotyping. The percentage of cells with fusion signals ranged from 20% to 80%. All fourteen patients positive for TEL/AML1 gene fusion were mosaic. Three out of the 14 patients positive for the TEL/AML1 gene fusion were originally reported to be culture failures and none of the remaining eleven samples had been found to have chromosome 12 abnormalities by conventional cytogenetic techniques. All pediatric patients with pre-T or T cell lineage and the six adults were negative for TEL/AML1 fusion. One patient had double Philadelphia chromosomes, three had a rearrangement or a deletion of the MLL gene, one had t(4; 11)and two had a deletion of the MLL. One of the patients with an MLL deletion also had a large ring of chromosome 21, and r(21)was caused by AML1 gene tandemly duplicated at least five times. The second case with the MLL deletion was also unique, the patient had a t(12; 21)as well. A total of 20 patients had numerical changes(gain or loss)of chromosomes 4, 10, 17 and 21. Eight patients were found to have trisomies of three or four different chromosomes. Interestingly, seven of these patients did not have TEL/AML1, BCR/ABL or the MLL gene rearrangement; one did have the TEL/AML1 gene fusion. Eleven patients with pro-B cell or B cell type ALL(9 children with ALL, 2 adults with ALL)had numerical changes of chromosome 21(gain 1 or 2 chromosome 21), among them, 10 patients had no structural alteration of chromosome 21, and one was combined by t(12; 21). Four patients had a monosomy of chromosome 17 and three out of these patients with monosomy 17 also had a fusion signal of TEL/AML1. Conclusions FISH plays an important role in detecting chromosome changes, especially in some cryptic chromosome translocations and patients with culture failures. This study found a trend towards a division between patients who had structural changes such as t(12; 21)or a ring chromosome 21 and those who had numerical changes of chromosome 21 as well as the patients with TEL/AML1 fusion and patients with the coexistence of numerical chromosomal changes of chromosomes 4, 10 and 17. In our opinion there are two separate mechanisms which lead to the development or progression of leukemia. Chin Med J 2003 ;116(9): 1298-1303

Objective To investigate the nasal carriage of antibiotic-resistant pneumococci in children of <5 years old in the following four cities, Beijing, Shanghai, Guangzhou and Xi'an. Methods A total of 647 pneumococci strains were isolated and detected. Minimal inhibition concentrations(MICs)of antibiotics were determined by E-test. Disk diffusion test was used for the measurement of antimicrobial susceptibility. Results Prevalence of penicillin non-susceptible Streptococcus pneumoniae in the four cities was 41 %, with Guangzhou(60. 8%)ranking first, followed by Xi'an(45%), Shanghai(37%)and Beijing(25.9%).The majority of penicillin non-susceptibility isolates(23. 9%-53. 8%)had a low level of resistance(MIC 0. 64-1. 5 μg/ml). The most sensitive antimicrobials in terms of percentage of susceptible organisms were amoxicillin-clavulanic acid(99. 4%), followed by ceftriaxone(92. 1%); cefurxime and cefaclor were slightly more sensitive than penicillin with susceptibility of 74. 8% and 77. 9%. Erythromycin, tetracycline and TMP-SMZ were highly resistant(83.6%, 82. 1% and 76. 2% respectively). Among erythromycin resistant isolates, 100% were resistant to azithromycin, 98. 6% to clarithromycin, 97. 2% to roxithromycin and spiramycin, and 96. 6% to clindamycin. 97. 2%(141/145)were typical of the macrolides-lincosamides-streptogramons B(MLSB)resistance phenotype, and 2. 8%(4/145)were M phenotype. The group of PRSP was with significantly higher rates of non-susceptibility for ceftriaxone(18.4%), cefurxime(58.6%), cefaclor(53.4%), compared with the group of PEN-S(0.5%, 1.8% and 0.2%, respectively)and the rate of multi-drug resistance in the isolates of PRSP group(92. 9%)was significantly higher than that of PEN-S group(59. 2%). Conclusion The rates of penicillin and multi-drug resistance among isolates of pneumococci carried nasally in are high children and the high prevalence of multi-drug resistance in the Chinese population may be becoming one of the most serious problems in this century. Chin Med J 2003;116(9): 1304-1307

Objectives To study the interaction of beta-2-glycoprotein I(β2GP I)with the membrane of hepatocytes and determine whether β2GP I participates in HBV infection. Methods Ligand blotting, fluorescence microscopy, and fluorescence activated cell sorter(FACS)analysis were used to detect the specific interaction of β2GP I with the hepatoma cell line smmc7721, the gastric carcinoma cell line SGC7901, and the lymphoma cell line HL-60. Results A specific 40 kDa β2GP I band was observed by ligand blotting in the case of smmc7721 cells. No such band was observed in SGC7901 or HL-60 cells. Fluorescence microscopy also revealed specific binding of FITC_β2GP I to smmc7721 cells, but neither to SGC7901 nor HL-60 cells. FACS analysis demonstrated that the binding rate of FITC_β2GP I to smmc7721 cells was significantly higher than these in SGC7901 and HL-60 cells(P<0. 01). The binding rate to smmc7721 cells did not increase with increasing amounts of FITC-β2GP I. Conclusions There is a specific β2GP I-binding protein on the membrane of hepatoma cells in cell line smmc7721 which as the β2GP I receptor may participate in HBV infection of hepatocytes. Chin Med J 2003;116(9): 1308-1311

Objective To study the clinical and histological features of chronic hepatitis B(CHB)with negative hepatitis B e-antigen(HBeAg). Methods A tatal of 743 in-patients with chronic hepatitis B were recruited into the study and divided into two groups according to the HBeAg status. The correlation among alanine transaminase(ALT)levels, hepatitis B virus(HBV)DNA semiquantification, and the liver histopathological data were dectected. Results Of the 743 successive in-patients, 267(35.9%)were HBeAg-negative. The HBDAG-negative group had significantly lower serologic HBV DNA levels(63.0% of<100 pg/ml)vs HBeAg-positive(42. 6 %, P<0.001), while more sever inflammation(58. 1 % of inflammatory scores of histological activeity index(HAlinf≥9)vs HBeAg-positive group(46.0%, P<0.001)and severe fibrosis(45.3% of fibrosis scores of histological activity index(HAIfib≥3)vs HBeAg-positive group(27.9%, P<0.001)of liver histology. In HBeAg-positive patients, increasing ALI levels were significantly associated with high inflammation and fiborsis scores and low HBV DNA levels. However, it was not the case in the HBeAg-negative cases. In HBeAg-positive patients, 91.3 % of them had HAIinf≥9 and 65.7% had HAIfib≥3 with HBV DNA〉100 pg/ml, while 8.2% of them had HAIinf≥9 and 12.3% had HAIfib≥3 with HBV DNA<20 pg/ml, indicating an obverse correlation between HBV DNA levels and histology scores. Conclusions As regards clinical and histological background, the chronic HBeAg-negative hepatitis B is a different subpopulation from the HBeAg-positive counterpart. Chin Med J 2003; 116(9): 1312-1317

Objective To confirm the close relationship of high co-infection rate between HIV and hepatitis virus in intravenous drug users(IVDUs). Methods Anti-HIV, HBV and HCV were detected by ELISA in the serum from 35 scattered and 15 massed IVDUs. PCR and RT-PCR were performed to confirm the infection of HIV, HBV, HCV, HGV and TTV among the 15 massed intravenous drug abusers. Results Among the 50 IVDUs, the positive rates of anti-HCV1 HBsAg, anti-HBe and anti-HBc were 92%(46/50), 12%(6/50), 10%(5/50)and 66%(33/50), respectively. In the samples of HBsAg positive, their HBeAg was also positive. Although the positive rate of serum markers was different in the massed IVDUs compared to the scattered IVDUs, no significant difference was shown. In the cases of massed IVDUs, the positive rates of HIV DNA, HBV-DNA, HCV-RNA, HGV-RNA, and TTV-DNA were 100%(15/15), 26.6%(4/15), 53. 3%(8/15), 33. 3%(5/15)and 26. 6%(4/15), respectively. Among the 15 massed intravenous drug users, one was infected with HIV, HBV, HCV, HGV and TTV; two were infected with HIV, HBV, HCV and HGV; three were infected only with HIV; and the remaining had other forms of co-infection. Conclusion The co-infection rate of HIV, HBV, HCV, HGV and TTV in intravenous drug users is very high. Chin Med J 2003;116(9): 1318-1320

Objective To study the apoptotic effects of influenza A virus on the Raji cell line. Methods Cultured Raji cells were infected with influenza A virus at a multiplicity of infection(m. o. i)of 20 and the effects of apoptosis were detected at different time points post infection using the following methods: electron microscope, DNA agarose gel electrophoresis, PI stained flow cytometry(FCM)and Annexin-V FITC/PI stained FCM. Results Raji cells infected with influenza A virus showed changes of morphology apoptotis, DNA agarose electrophoresis also demonstrated a ladder-like pattern of DNA fragments in a time-dependent manner. PI stained FCM showed "apoptosis peak" and FITC/PI stained FCM showed apoptotic cells. Quantitative analysis indicated that the percentage of apoptotic Raji cells increased after infection, and cycloheximide(CHX), an eukaryotic transcription inhibitor, could effectively inhibit the apoptotic effects of influenza A virus in vitro. Conclusions Influenza A virus can induce apoptosis in Raji cell line suggesting that it may lead to a potential method for tumor therapy. Chin Med J 2003; 116(9): 1321-1324

Objective To determine the feasibility and efficiency of terminating atrial flutter(AFL)and atrial fibrillation(AF)using synchronous low-energy shocks delivered through a novel transesophageal electric balloon electrode system. Methods By using a novel electric balloon electrode system, we attempted 91 transesophageal cardioversions in 52 patients, to treat 53 episodes of AFL and 38 episodes of AF. Results Of the 40 patients of AFL that failed to respond to drug therapy, 37(92.5%)were successfully countershocked to sinus rhythm by transesophageal cardioversion, with a mean energy of(22. 70±4. 50)J(20-30 J). Of the 19 patients in AF, transesophageal cardioversion was successful in 16(84. 2%)cases, requiring a mean delivered energy of(17. 38 ± 8. 58)J(3-30 J). There were no complications such as heart block or ventricular fibrillation, and no evidence of esophageal injury. Conclusions Transesophageal cardioversion using an electric balloon electrode system is an effective and feasible method for the treatment of AFL and AF. It requires low energy and no anesthesia, leads to less trauma, and shows a high cardioversion success rate that may prove valuable in the management of tachyarrhythmias. Chin Med J 2003;116(9): 1325-1328

Purpose To review the characteristics and evolution of the fungal spectrum, and the risk factors causing fungal infection, and to make progress in diagnosing fungal infection after organ transplantation. Data sources An English-language literature search(MEDLINE 1990-2000)and bibliographic review of textbooks and review articles. Study selection Twenty-three articles were selected from the literature that specifically addressed the stated purpose. Results Fungal infections in organ transplant patients were generally divided into two types: ①disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses; ② opportunistic infection by fungal species that rarely cause invasive infection in normal hosts. The risk factors of fungal infection after a transplant can be evaluated and predicted according to the organ recipient's conditions before, during and after the transplant. Progress in early diagnostic methods during the past 10 years has mainly revolved around two aspects, culture and non-culture. Conclusions It is important to undertake a systemic evaluation on the condition of the organ recipient before, during and after a transplant; should any risk factor for fungal infection be suspected, diagnosis should be made as early as possible by employing mycological techniques including culture and non-culture methods. Chin Med J 2003; 116(9): 1421-1425

Objectives To characterize the prethrombotic state(PTS)in elderly Chinese patients with obstructive sleep apnea hypopnea syndrome(OSAHS)and the effect of nasal continuous positive airway pressure(nCPAP)ventilation on their PTS. Methods Forty-one elderly patients with moderate and severe OSAHS were enrolled into the OSAHS group and underwent nCPAP treatment. Their blood samples were drawn at 6:00 am and 4:00 pm before and during nCPAP treatment, respectively, to test hemocrit, platelet aggregation(PAG), whole blood viscosity(WBV), plasma fibrinogen(fng), prothrombin time(PT)and activated partial thromboplastin time(APTT). All blood factors were also tested in a control group consisting of 32 healthy elderly Chinese with neither OSAHS nor cerebrocardiac vascular disease. Results In the OSAHS group there was a significantly higher hemocrit, WBV, fng, and a significantly shorter PT and APTT at 6: 00 am compared to 4: 00 pm before nCPAP treatment, while there was no significant difference among all blood test factors between 6:00 am and 4:00 pm on day 30 of the nCPAP treatment. In the OSAHS group, the hemocrit, WBV, PAG and plasma fng were significantly lower and the PT and APTT were significantly longer at 6: 00 am on day 30 of the nCPAP treatment compared to 6: 00 am before the nCPAP treatment. A significantly lower hemocrit, but a much longer PT and APTT were observed at 4:00 pm on day 30 of the treatment, compared with 4:00 pm before the treatment. No significant difference among the blood test factors was found between 6:00 am and 4:00 pm blood in the control group or between the control and OSAHS groups after 30 days of nCPAP treatment. Conclusion In elderly Chinese OSAHS patients, PTS could be effectively eliminated by nCPAP treatment. Chin Med J 2003; 116(9): 1426-1428