Identification and characterization of novel serum microRNAs in unstable angina pectoris and subclinical atherosclerotic patients.

BACKGROUND: MicroRNAs (miRNAs) are involved in cardiac developmental and pathological processes, and serum profile is useful for identifying novel miRNAs. METHODS AND RESULTS: Serum samples were collected from unstable angina pectoris (UAP) and subclinical atherosclerotic (AS) patients. Solexa sequencing was used to predict novel miRNAs in 15 control individuals, 15 AS patients and 15 UAP patients. After bioinformatics analysis and filtering out in the newest version of miRbase (version 20.0), three novel miRNAs were validated in 80 control individuals, 80 AS patients and 80 UAP patients by quantitative reverse transcriptase polymerase chain reaction. Two of the three novel microRNAs (N1 and N3) were expressed at the highest levels in the AS group. N1 had an area under curve (AUC) of 0.811 (95% confidence interval 0.743-0.880) for AS. N3 showed a moderate separation with an area under curve (AUC) of 0.748 (95% confidence interval 0.664-0.833) for AS. Combined the two novel microRNAs can significantly distinguish AS from control. CONCLUSIONS: Three novel miRNAs were identified by Solexa sequencing and two of them may be new potential predictors for arthrosclerosis.

The correlation between serum lipid profile with carotid intima-media thickness and plaque.

BACKGROUND: It is indicated that non-HDL cholesterol and lipid ratios, including total/HDL cholesterol and LDL/HDL cholesterol ratios, are risk indicators with greater predictive value for coronary atherosclerotic progression or regression compared with conventional lipid profile. However, there have been few reports about the correlation between serum lipid profile with carotid intima-media thickness (IMT) and plaque in Chinese general people. METHODS: We examined 402 subjects without apparent diseases in a cross-sectional study (mean age 50.16 years; 36.07% female). Demographics, anthropometrics, and laboratory data were collected. The presence of carotid plaque and intima-media thickness were evaluated by ultrasonography. RESULTS: Univariate correlations showed carotid IMT was correlated with LDL-C (r = 0.137, p = 0.009), non-LDL-C levels (r = 0.140, p = 0.008) and LDL-C/HDL-C ratio (r = 0.169, p = 0.001). After adjustment for potential covariates, LDL-C/HDL-C ratio (ß = 0.132, p < 0.001) were independent variables that interacted on carotid IMT. Other risk factors including age and systolic blood pressure were independently associated with carotid IMT. LDL-C levels, non-HDL-C levels, TC/HDL-C and LDL-C/HDL-C ratios were significantly higher, but HDL-C levels were significantly lower in subjects with carotid plaque than those without it. The subsequent multiple logistic regression analysis showed that LDL-C (OR; 1.325, 95% CI; 1.046-1.821, p = 0.033) and HDL-C levels (OR; 0.093, 95% CI; 0.038-0.227, p < 0.001) were significantly associated with the presence of carotid plaque after adjustment of age. Furthermore, LDL-C combined with HDL-C levels showed the highest area under the curve (0.788, 95% CI; 0.740-0.837, p < 0.001). CONCLUSIONS: Serum LDL-C/HDL-C ratio represents as an independent index associated with increased carotid IMT and LDL-C combined with HDL-C levels may be useful markers for predicting the presence of carotid plaque in the Chinese general population.

Hematopoietic stem cell transplantation for treatment of patients with leukemia concomitant with active tuberculosis infection.

BACKGROUND: Currently, hematopoietic stem cell transplantation is still an essential treatment approach for leukemia. However, patients with leukemia often have weakened immune function, especially more seriously compromised cellular immune response, and appear to be at greater risk for tuberculosis infection during the transplantation process. We aimed to investigate the efficacy and safety of hematopoietic stem cell transplantation for the treatment of patients with leukemia accompanying active tuberculosis infection. MATERIAL/METHODS: We retrospectively analyzed records of 7 consecutive patients who were diagnosed with leukemia concomitant with active tuberculosis infection and who underwent hematopoietic stem cell transplantation in our hospital from January 2006 to December 2012. RESULTS: Among these 7 patients (4 males and 3 females; median age: 38 years; range: 30-46 years), the mean duration of anti-TB treatment before transplantation was 3 months (range: 2-4.5 months). All patients acquired engraftment, with an implantation rate of 100%. After transplantation, the mean duration of anti-TB treatment was 12 months. All patients had response after receiving anti-TB treatment. One patient died of leukemia relapse 6 months after the transplantation, but no tuberculosis infection-related death was reported. CONCLUSIONS: Patients with leukemia concomitant with active tuberculosis infection can be treated with hematopoietic stem cell transplantation if they receive an effective anti-TB treatment regimen. The anti-TB treatment regimen had no effect against hematopoietic stem cell transplantation and was well-tolerated. All post-transplanted patients experienced no relapse of tuberculosis during the immune-suppression period. The findings in the present investigation deserve further in-depth study.

The clinical performance evaluation of novel protein chips for eleven biomarkers detection and the diagnostic model study.

We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r≥0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro-GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and ß-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance.

In vitro activity of linezolid against clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains from Beijing, China.

The in vitro activity of linezolid was evaluated against 84 clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, isolated from the center for tuberculosis research and treatment of the Chinese army. Linezolid showed excellent activity, with minimum inhibitory concentrations (MICs) of 0.125-0.5 µg/mL against all tested isolates. There were no differences in the MIC(50) and MIC(90) of linezolid between susceptible, isoniazid-resistant, MDR, and XDR. Indeed, all of the groups displayed identical MIC(90) values of 0.25 µg/mL, which is lower than previously reported in similar studies. We conclude that linezolid may be a more effective drug against M. tuberculosis and may play an important role in treating drug-resistant tuberculosis in China.

In vitro efficacy of acetohydroxyacid synthase inhibitors against clinical strains of Mycobacterium tuberculosis isolated from a hospital in Beijing, China.

OBJECTIVE: To assess the efficacy of acetohydroxyacid synthase (AHAS) inhibitors against Mycobacterium tuberculosis from China, including multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. METHODS: In this study, the tube dilution method and Middlebrook 7H10 agar media were used to describe the in vitro efficacy of 3 AHAS inhibitors (sulfometuron methyl, monosulfuron, and monosulfuron-ester) against H37Rv and 26 clinical isolates, which include MDR-TB and XDR-TB strains, from the 309th Hospital of Chinese People's Liberation Army (PLA 309), Beijing, China. Cytotoxity of these compounds were then evaluated using the 3-[4,5-dimethylthiazol-2yl]-2,5-dipheny tetrazolium bromide assay with HBE cells. All the experiments were performed from January 2010 to November 2010 in the Department of Clinical Laboratory of the PLA 309 hospital. RESULTS: Sulfometuron methyl (minimum inhibitory concentration [MIC] range, 8-16 mg/L), monosulfuron-ester (MIC range, 8-16 mg/L), and monosulfuron (MIC range, 16-64 mg/L) showed significant activity against all Mycobacterium tuberculosis strains tested in this study in vitro, and they exhibited the same degree of activity against MDR and XDR isolates with that shown against the susceptible strains. All 3 compounds showed little cytotoxicity, with an IC50 against HBE cells greater than 300 mg/L. CONCLUSION: The results suggest that AHAS could serve as a target protein for the development of novel anti-TB therapeutics in China.

Antimicrobial susceptibility patterns of clinical isolates of gram-negative bacteria obtained from intensive care units in a tertiary hospital in Beijing, China.

In this study we investigated the prevalence of antimicrobial resistance in clinical isolates of Gram-negative bacteria obtained from intensive care units (ICUs) in the People's Liberation Army (PLA) 309 Hospital located in beijing, China. between 2007 and 2010, a total of 1949 isolates of Gram-negative bacteria were collected and tested using an antibiotic susceptibility assay. A marked decrease was observed in the susceptibility of Acinetobacter baumannii to imipenem and amikacin as compared to that described in a previous report in China. Similar results were obtained for Pseudomonas aeruginosa. However, imipenem and amikacin showed strong activity against Escherichia coli and Klebsiella pneumoniae. Overall, the high rates of antimicrobial resistance against ICU pathogens in our hospital indicated a critical condition in Beijing, China. Development of a national control and monitoring system by the government may be an ideal method to solve the present problem of managing infections due to Gram-negative bacterial pathogens.

Prevalence of multidrug and extensively drug-resistant tuberculosis in Beijing, China: a hospital-based retrospective study.

Tuberculosis (TB) is a disease of worldwide public-health concern. The development of resistance to an increasing number of second-line drugs and those used to treat multidrug-resistant (MDR) TB is rapidly becoming an emergency that could hinder the prevention and treatment of TB globally. This study describes the resistance profile of MDR and extensively drug-resistant (XDR) TB with a hospital-based survey in Beijing, China, conducted in the period 2007 to 2009. Drug-susceptibility tests performed on 967 Mycobacterium tuberculosis strains isolated from 967 patients showed that the rate of resistance to at least one first-line and at least one second-line drug was 70.1% and 60.7%, respectively. The overall MDR rate was 19.4%, and 14.9% of the MDR cases were XDR. In conclusion, MDR and XDR TB represent a significant number of total TB cases, therefore effective measures to manage these resistant strains are desperately needed. Development of a national TB policy in China might be a key method for solving the present problems of TB management.