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1.  GenoType MTBDRplus Assay for Rapid Detection of Multidrug Resistance in Mycobacterium tuberculosis: A Meta-Analysis 
PLoS ONE  2016;11(3):e0150321.
There is an urgent demand for rapid and accurate drug-susceptibility testing for the detection of multidrug-resistant tuberculosis. The GenoType MTBDRplus assay is a promising molecular kit designed for rapid identification of resistance to first-line anti-tuberculosis drugs, isoniazid and rifampicin. The aim of this meta-analysis was to evaluate the diagnostic accuracy of GenoType MTBDRplus in detecting drug resistance to isoniazid and rifampicin in comparison with the conventional drug susceptibility tests.
We searched PubMed, EMBASE, and Cochrane Library databases to identify studies according to predetermined criteria. A total of 40 studies were included in the meta-analysis. QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curves. Heterogeneity in accuracy measures was tested with Spearman correlation coefficient and Chi-square.
Patient selection bias was observed in most studies. The pooled sensitivity (95% confidence intervals were 0.91 (0.88–0.94) for isoniazid, 0.96 (0.95–0.97) for rifampicin, and 0.91(0.86–0.94) for multidrug-resistance. The pooled specificity (95% CI) was 0.99 (0.98–0.99) for isoniazid, 0.98 (0.97–0.99) for rifampicin and 0.99 (0.99–1.00) for multidrug-resistance, respectively. The area under the summary receiver operating characteristic curves ranged from 0.99 to 1.00.
This meta-analysis determined that GenoType MTBDRplus had good accuracy for rapid detection of drug resistance to isoniazid and/or rifampicin of M. tuberculosis. MTBDRplus method might be a good alternative to conventional drug susceptibility tests in clinical practice.
PMCID: PMC4774872  PMID: 26934724
2.  Relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma 
The purpose of this study is to assess the relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma.
We enrolled 65 consecutive patients with meningioma and 31 normal controls matched for age, gender, and education. The patients were divided into frontal or non-frontal (NF) meningioma groups based on magnetic resonance imaging; the frontal group was then subdivided to dorsolateral frontal (DLF), medial frontal (MF), and ventral frontal (VF) groups. Tumor size and brain edema were also recorded. Apathy was assessed by the Apathy Evaluation Scale (AES). Assessments were carried out 1 week before and 3 months after surgery, respectively. Logistic regression analysis was performed to identify the predictive effect of tumor size, location, and brain edema on apathy. Analysis of variance and chi-square analysis were applied to compare apathy scores and apathy rates among the frontal, NF, and normal control groups, and all subgroups within the frontal group.
Compared with the NF and control groups, the mean AES score was much higher in the frontal group (34.0±8.3 versus 28.63±6.0, P=0.008, and 26.8±4.2, P<0.001). Subgroup analysis showed that AES scores in the MF group (42.1±6.6) and VF group (34.7±8.0) were higher than in the DLF group (28.5±4.36), NF group, and control group (P<0.05). The apathy rate was 63.6% in the MF group and 25% in the VF group, and significantly higher than in the DLF (5.6%), NF (5.3%), and control (0%) groups (P<0.001). A moderate correlation was found between AES score and mean diameter of the meningioma in all patient groups. Further analysis demonstrated that the correlation existed in the DLF (r=0.52, P=0.032), MF (r=0.84, P<0.001), and VF (r=0.64, P=0.008) groups, but not in the NF group (r=0.19, P=0.448). The AES score was much higher in patients with brain edema than in those without brain edema (34.73±8.28 versus 28.77±4.20, t=3.545, P=0.001). In subgroups within frontal meningioma patients, the statistical significance above only existed in the MF group (43.50±5.26 versus 25.67±6.03, P=0.001). Also, we examined the effect of related factors, such as age, sex, education, tumor size, tumor location and edema on the occurrence of apathy. The binary logistic regression analysis showed that MF [P=0.023, Exp(B) =145.6] and size [P=0.012, Exp(B) =1.20] got into the regression equation. Thirty-two patients underwent follow-up post-surgery. A significant reduction in AES was found in the MF group (AES1 – AES2 =6.86±6.82, t=2.68, P=0.04), but not in any of the other groups.
Apathy occurs frequently in patients with frontal meningioma, and is more severe, especially in the MF region. Apathy is probably correlated with tumor location and size. Brain edema might increase the severity of apathy.
PMCID: PMC4508073  PMID: 26203250
apathy; Apathy Evaluation Scale; meningioma; edema; location; size
3.  Helicobacter pylori Outer Membrane Protein 18 (Hp1125) Is Involved in Persistent Colonization by Evading Interferon-γ Signaling 
BioMed Research International  2015;2015:571280.
Outer membrane proteins (OMPs) can induce an immune response. Omp18 (HP1125) of H. pylori is a powerful antigen that can induce significant interferon-γ (IFN-γ) levels. Previous studies have suggested that IFN-γ plays an important role in H. pylori clearance. However, H. pylori has multiple mechanisms to avoid host immune surveillance for persistent colonization. We generated an omp18 mutant (H. pylori 26695 and H. pylori SS1) strain to examine whether Omp18 interacts with IFN-γ and is involved in H. pylori colonization. qRT-PCR revealed that IFN-γ induced Omp18 expression. qRT-PCR and western blot analysis revealed reduced expressions of virulence factors CagA and NapA in H. pylori 26695 with IFN-γ treatment, but they were induced in the Δomp18 strain. In C57BL/6 mice infected with H. pylori SS1 and the Δomp18 strain, the Δomp18 strain conferred defective colonization and activated a stronger inflammatory response. Signal transducer phosphorylation and transcription 1 (STAT1) activator was downregulated by the wild-type strain but not the Δomp18 strain in IFN-γ-treated macrophages. Furthermore, Δomp18 strain survival rates were poor in macrophages compared to the wild-type strain. We concluded that H. pylori Omp18 has an important function influencing IFN-γ-mediated immune response to participate in persistent colonization.
PMCID: PMC4402576  PMID: 25945338
4.  Outbreak of Multidrug Resistant NDM-1-Producing Klebsiella pneumoniae from a Neonatal Unit in Shandong Province, China 
PLoS ONE  2015;10(3):e0119571.
Despite worldwide dissemination of New Delhi metallo-β-lactamase1 (blaNDM-1), outbreaks remain uncommon in China. In this study, we describe the characteristics of the outbreak-related blaNDM-1-producing K. pneumonia isolates in a neonatal unit in Shandong province, China. We recovered 21 non-repetitive carbapenem-resistant K. pneumoniae isolates with a positively modified Hodge test (MHT) or EDTA synergistic test from patients and environmental samples in Shandong provincial hospital. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) data show K. pneumoniae isolates from 19 patients were clonally related and belong to the clonal groups ST20 and ST17. We note two outbreaks, the first caused by ST20 during August 2012 involving four patients, and the second caused by ST20 and ST17 during January 2012 and September 2013 involving fourteen patients. We found the bed railing of one patient was the source of the outbreak. We verified the presence of the blaNDM-1 gene in 21 K. pneumoniae isolates. The genes blaCTX-M-15, blaCTX-M-14, blaDHA-1, blaTEM-1 and Class I integron were also present in 18 (85.7%), 3 (14.3%), 18 (85.7%), 19 (90.5%) and 19 (90.5%) isolates, respectively. We also found an isolate with both blaNDM-1 and blaIMP-4. All of the isolates exhibited a multidrug-resistance phenotype. The β-lactam resistance of 20 isolates was transferable via conjugation. In addition, we show the resistance of 21 K. pneumoniae isolates to carbapenem is not related to lack of outer-membrane proteins OmpK35 and OmpK36 nor overpression of efflux pumps. This study provides the first report confirming blaNDM-1-producing K. pneumoniae ST20 and ST17 were associated with outbreak. Early detection of resistance genes is an effective strategy in preventing and controlling infection by limiting the dissemination of these organisms.
PMCID: PMC4370709  PMID: 25799421
5.  An open science resource for establishing reliability and reproducibility in functional connectomics 
Zuo, Xi-Nian | Anderson, Jeffrey S | Bellec, Pierre | Birn, Rasmus M | Biswal, Bharat B | Blautzik, Janusch | Breitner, John C.S | Buckner, Randy L | Calhoun, Vince D | Castellanos, F. Xavier | Chen, Antao | Chen, Bing | Chen, Jiangtao | Chen, Xu | Colcombe, Stanley J | Courtney, William | Craddock, R Cameron | Di Martino, Adriana | Dong, Hao-Ming | Fu, Xiaolan | Gong, Qiyong | Gorgolewski, Krzysztof J | Han, Ying | He, Ye | He, Yong | Ho, Erica | Holmes, Avram | Hou, Xiao-Hui | Huckins, Jeremy | Jiang, Tianzi | Jiang, Yi | Kelley, William | Kelly, Clare | King, Margaret | LaConte, Stephen M | Lainhart, Janet E | Lei, Xu | Li, Hui-Jie | Li, Kaiming | Li, Kuncheng | Lin, Qixiang | Liu, Dongqiang | Liu, Jia | Liu, Xun | Liu, Yijun | Lu, Guangming | Lu, Jie | Luna, Beatriz | Luo, Jing | Lurie, Daniel | Mao, Ying | Margulies, Daniel S | Mayer, Andrew R | Meindl, Thomas | Meyerand, Mary E | Nan, Weizhi | Nielsen, Jared A | O’Connor, David | Paulsen, David | Prabhakaran, Vivek | Qi, Zhigang | Qiu, Jiang | Shao, Chunhong | Shehzad, Zarrar | Tang, Weijun | Villringer, Arno | Wang, Huiling | Wang, Kai | Wei, Dongtao | Wei, Gao-Xia | Weng, Xu-Chu | Wu, Xuehai | Xu, Ting | Yang, Ning | Yang, Zhi | Zang, Yu-Feng | Zhang, Lei | Zhang, Qinglin | Zhang, Zhe | Zhang, Zhiqiang | Zhao, Ke | Zhen, Zonglei | Zhou, Yuan | Zhu, Xing-Ting | Milham, Michael P
Scientific Data  2014;1:140049.
Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals’ resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.
PMCID: PMC4421932  PMID: 25977800
6.  The impact of educational status on the clinical features of major depressive disorder among Chinese women 
Journal of Affective Disorders  2012;136(3):988-992.
Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting.
Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD.
Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide.
Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample.
The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD.
PMCID: PMC3314924  PMID: 21824664
Major depressive disorder; Education; Socio-economic status; Symptom
7.  Possible association of decreased NKG2D expression levels and suppression of the activity of natural killer cells in patients with colorectal cancer 
International Journal of Oncology  2011;40(4):1285-1290.
Natural-killer group 2 (NKG2), a natural killer (NK) cell receptor, plays a critical role in regulating NK cytotoxicity. In this study, we investigated the expression levels of natural killer group 2 member A (NKG2A) and natural killer group 2 member D (NKG2D) in NK cells as well as the regulatory function of NKG2D in patients with colorectal cancer (CRC). Sixty-two CRC patients and 32 healthy controls were enrolled in this study. The expression levels of NKG2A and NKG2D mRNA in peripheral blood mononuclear cells (PBMCs) were investigated using real-time PCR. Flow cytometry was performed to assay the levels of NKG2A and NKG2D proteins in NK cells. The levels of NKG2D mRNA in PBMCs in the patients were significantly lower than those in the controls [mean ± SD, 1.11±0.60 (CRC patients) vs. 1.65±0.71 (healthy controls); p<0.01], whereas the 2 groups showed no apparent difference in the levels of NKG2A mRNA (p>0.05). In addition, the patients showed significantly lower NKG2D levels in NK cells than the controls did (71.23%±8.31% [CRC patients] vs. 79.39%±5.58% [healthy controls]; p<0.01). However, we observed no distinct difference in the NKG2A expression levels in NK cells between the 2 groups (p>0.05). Notably, blockage of NKG2D signaling with anti-NKG2D antibodies ex vivo resulted in decreased cytotoxicity and CD107a degranulation. Our data revealed that the decrease in NKG2D expression levels may have been associated with suppression of NK cell activity in CRC patients.
PMCID: PMC3584522  PMID: 22200673
NKG2; natural killer cells; colorectal cancer; suppression
8.  Age at onset of major depressive disorder in Han Chinese women: Relationship with clinical features and family history☆ 
Journal of Affective Disorders  2011;135(1-3):89-94.
Individuals with early-onset depression may be a clinically distinct group with particular symptom patterns, illness course, comorbidity and family history. This question has not been previously investigated in a Han Chinese population.
We examined the clinical features of 1970 Han Chinese women with DSM-IV major depressive disorder (MDD) between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models was used to determine the association between age at onset (AAO) with continuous, binary and discrete characteristic clinical features of MDD.
Earlier AAO was associated with more suicidal ideation and attempts and higher neuroticism, but fewer sleep, appetite and weight changes. Patients with an earlier AAO were more likely to suffer a chronic course (longer illness duration, more MDD episodes and longer index episode), increased rates of MDD in their parents and a lower likelihood of marriage. They tend to have higher comorbidity with anxiety disorders (general anxiety disorder, social phobia and agoraphobia) and dysthymia.
Early AAO in MDD may be an index of a more severe, highly comorbid and familial disorder. Our findings indicate that the features of MDD in China are similar to those reported elsewhere in the world.
PMCID: PMC3210897  PMID: 21782247
Major depressive disorder; Age at onset; Symptom; Comorbidity
9.  Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin 
Journal of Clinical Investigation  2006;116(2):506-511.
Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2 — resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes — is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30–50% of whom possess the inactive ALDH2*2 mutant allele.
PMCID: PMC1351000  PMID: 16440063

Results 1-9 (9)