Vacancy-Induced Antibacterial Activity of XS2-y Quantum Dots against Drug-Resistant Bacteria for Treatment of Bacterial Keratitis.

Due to the widespread antibiotic-resistant microbes and the slow development in antibiotics, innovative new antibacterial agents are eagerly desired to control infection in the resistance era. Here, it is demonstrated that the antibacterial ability against drug-resistant bacteria can be endowed to transition metal dichalcogenides (XS2 , X = Mo/W) quantum dots by sulfur vacancies, and their application in bacterial keratitis. The sulfur vacancies are generated by the ion irradiation with the controlled influences, which ensures the one-way electron transport from the external environment to XS2 leading to a strong reactive oxygen speciesindependent oxidative stress. With the concentration of 140 µg mL-1 of XS2-0.1 quantum dots, the sterilization efficiency of Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus more than 99.9% within 20 min at room temperature in the dark is realized. For biomedical application against bacterial keratitis, it is observed that the occurrence of severe clinical manifestation like ocular perforation can be prevented. This work demonstrates the vacancy as a novel, simple, and effective strategy to tune XS2 as the antibacterial agent with a fast response and no reliance on light that has significant potential therapeutic effects on clinical drug resistant bacterial keratitis.

WDHD1 facilitates G1 checkpoint abrogation in HPV E7 expressing cells by modulating GCN5.

BACKGROUND: Genomic instability is a hallmark of cancer. The G1 checkpoint allows cells to repair damaged DNA that may lead to genomic instability. The high-risk human papillomavirus (HPV) E7 gene can abrogate the G1 checkpoint, yet the mechanism is still not fully understood. Our recent study showed that WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein 1) plays a role in regulating G1 checkpoint of E7 expressing cells. In this study, we explored the mechanism by which WDHD1 regulates G1 checkpoint in HPV E7 expressing cells. METHODS: NIKS and RPE1 derived cell lines were used. Real-time PCR, Rescue experiment, FACS and BrdU labeling experiments were performed to examine role of GCN5 in G1 checkpoint abrogation in HPV-16 E7 expressing cells. RESULTS: In this study, we observed that WDHD1 facilitates G1 checkpoint abrogation by modulating GCN5 in HPV E7 expressing cells. Notably, depletion of WDHD1 caused G1 arrest while overexpression of GCN5 rescued the inhibitory effects of WDHD1 knockdown on G1/S progression. Furthermore, siWDHD1 significantly decreased cell cycle proliferation and DNA synthesis that was correlated with Akt phosphorylation (p-Akt), which was reversed by GCN5 overexpression in HPV E7 expressing cells. CONCLUSIONS: In summary, our data identified a WDHD1/GCN5/Akt pathway leading to the abrogation of G1 checkpoint in the presence of damaged DNA, which may cause genomic instability and eventually HPV induced tumorigenesis.

National Surveillance of Legionnaires' Disease, China, 2014-2016.

We report national surveillance of Legionnaires' disease in China. Urine samples from 11 (3.85%) of 286 patients with severe pneumonia of unknown cause were positive for the Legionella pneumophila serogroup 1 antigen. We isolated Legionella strains from 7 patients. Improved diagnostic testing is needed for this underestimated disease in China.

Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Data for a total of 164 bloodstream infection cases due to carbapenem-resistant Enterobacteriaceae (CRE) from 2013 to 2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate the outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infecting species was Klebsiella pneumoniae (69.5%, 114/164). The overall in-hospital and 14-day mortality rates were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR], 6.339; 95% confidence interval [CI], 1.586 to 25.332; P = 0.009), the Pitt bacteremia score (aOR, 1.300; 95% CI, 1.009 to 1.676; P = 0.042), and the Charlson comorbidity index (aOR, 1.392; 95% CI, 1.104 to 1.755; P = 0.005) were independently associated with a hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy, resulted in relatively low rates of in-hospital mortality and failure in clearance of CRE infection. Survival analysis revealed that appropriate therapy was associated with a lower 14-day mortality rate than inappropriate therapy (including nonactive therapy; P = 0.022), that combination therapy was superior to monotherapy (P = 0.036), that metallo-ß-lactamase producers were associated with a lower 14-day mortality than strains without carbapenemases or KPC-2 producers (P = 0.009), and that strains with MICs of >8 mg/liter for meropenem were associated with a higher 14-day mortality rate than those with MICs of ≤8 mg/liter (P = 0.037). Collectively, the severity of illness, meropenem MICs of >8 mg/liter, and carbapenemase-producing types were associated with the clinical outcome. Early detection of the carbapenemase type and initiation of appropriate combination therapy within 96 h might be helpful for improving survival.

Phenotypic and Genotypic Characterization of Carbapenem-resistant Enterobacteriaceae: Data From a Longitudinal Large-scale CRE Study in China (2012-2016).

Background: Carbapenem-resistant Enterobacteriaceae (CRE) strains are a major threat to global health. The development of effective control measures requires more detailed phenotypic and genotypic characterization of CRE. Methods: CRE isolates were collected from 65 hospitals in 25 provinces across China between January 1, 2012, and December 31, 2016. The isolates were characterized by antimicrobial susceptibility testing and multilocus sequence typing. Genes encoding carbapenemases, mobilized colistin resistance (mcr-1), and ß-lactamases were detected by polymerase chain reaction and DNA sequencing. Results: A total of 1801 independent CRE isolates (1201 Klebsiella pneumoniae, 282 Escherichia coli, and 179 Enterobacter cloacae) were collected during the study period. Overall, 96.9%, 89.7%, 54.5%, 49.9%, and 40% of CRE strains were susceptible to colistin, tigecycline, amikacin, minocycline, and fosfomycin, respectively. Notably, 1091/1201 (91%) K. pneumoniae, 225/282 (80%) E. coli, and 129/179 (72%) E. cloacae harbored carbapenemase gene. K. pneumoniae carbapenemase (KPC) was predominant in K. pneumoniae (77%), whereas New Delhi metallo-ß-lactamase (NDM) was predominant in E. coli (75%) and E. cloacae (53%). The mcr-1 gene was detected in 13 NDM-carrying E. coli isolates (4.6%). Sequence type (ST)11 and ST167 were predominant among the 100 K. pneumoniae and 47 E. coli STs, respectively. KPC-ST11, which accounted for 64% of K. pneumoniae isolates, had higher levels of resistance than non-ST11 strains to aztreonam, fosfomycin, and amikacin (P < .001). The proportions of KPC and NDM enzymes in CRE increased from 2012 to 2016 (54%-59% and 12%-28%, respectively). Conclusions: The number of CRE strains harboring carbapenemase is increasing. KPC-ST11 K. pneumoniae, the predominant strain, shows a reduced susceptibility to most available antibiotics.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network.

Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible Citrobacter freundii, Escherichia coli, Enterobacter cloacae, or Klebsiella pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by K. pneumoniae (73.9%), followed by E. coli (16.6%) and E. cloacae (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against E. coli than against K. pneumoniae (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among K. pneumoniae and E. coli The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.

Viral aetiology in adults with acute upper respiratory tract infection in Jinan, Northern China.

Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14-25-year-old group than in the 26-65-year-old group. Codetection rates were higher (7.52%) in the 14-25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.

[Analysis of resistance tendency of bloodstream-infecting pathogens in China].

OBJECTIVE: To investigate the resistance profiles and the trend of bloodstream-infecting pathogens isolated from hospitalized patients during 2004-2010. METHODS: The bloodstream isolates were collected from 18 hospitals in 17 cities. Minimum inhibition concentrations (MIC) were determined using the agar dilution method recommended by CLSI (Clinical and Laboratory Standards Institute), and susceptibility results were analyzed according to the 2011 CLSI guideline. RESULTS: Among the 2004-2005, 2007-2008 and 2009-2010 periods, the proportions of clinical isolates were similar; 43.1% (149 isolates), 34.0% (151 isolates) and 47.5% (776 isolates) for Gram positive strains, 56.9% (197 isolates), 66.0% (293 isolates) and 52.5% (858 isolates) for Gram negative strains, respectively. The isolating rate of MRSA was 54.1% (20/37) in 2007-2008, which was the highest among the 3 periods during 2004 to 2010, while it decreased in 2009-2010 (36.5%, 62/170). The MRCNS proportions were similar across the 3 periods. One (1.8%) vancomycin-resistant Enterococcus faecium and 1 linezolid-resistant Enterococcus faecalis were found. Although the isolating rates of penicillin non-sensitive strains (oral) were similar between 2009-2010 and 2007-2008 [54.5% (6/11) and 53.9% (7/13), respectively], the resistant rates increased from 0% in 2007-2008 to 30.8% (4/13) in 2009-2010. The results were similar according to the non-meningitis criterion (IV), and the susceptibility rates decreased from 100.0% (11 isolates) in 2007-2008 to 84.6% (11/13) in 2009-2010. ESBL-harboring strains in E. coli were similar among the 3 periods during 2004 to 2010 [66.7% (30/45), 73.2% (71/97) and 67.9% (233/343), respectively]. ESBL-producing strains in Klebsilla pnuemoniae decreased year after year, 72.4% (21/29), 50.0% (18/36) and 41.1% (65/158) in 2004-2005, 2007-2008 and 2009-2010, respectively. Except that the sensitive rate of Enterobacter cloacae to ertapenem was 80% (32/40), the sensitive rates of other strains to carbapenems were still above 90% and the resistance rates were less than 5%. Acinetobacter baumannii had the highest multi-drug resistance rate (81.8%, 81/99). One strain (1.0%, 1/99) of Acinetobacter baumannii isolated in 2009-2010 was reported to be pan-resistant. CONCLUSIONS: We are facing a more serious situation of bacterial resistance. Acinetobacter baumannii resistance was most serious, usually with the characteristics of multiple drug resistance, and even pan-resistance. Carbapenems remain to be the most effective against enterobacteriaceae. Strains resistant to novel antibiotics (linezolid and tigecycline) have emerged.

Sensitivity evaluation of 2019 novel coronavirus (SARS-CoV-2) RT-PCR detection kits and strategy to reduce false negative.

The early detection and differential diagnosis of respiratory infections increase the chances for successful control of COVID-19 disease. The nucleic acid RT-PCR test is regarded as the current standard for molecular diagnosis. However, the maximal specificity confirmation target ORF1ab gene is considered to be less sensitive than other targets in clinical application. In addition, recent evidence indicated that the initial missed diagnosis of asymptomatic patients with SARS-CoV-2 and discharged patients with "re-examination positive" might be due to low viral load, and the ability of rapid mutation of SARS-CoV-2 also increases the rate of false-negative results. Moreover, the mixed sample nucleic acid detection is helpful in seeking out the early community transmission of SARS-CoV-2 rapidly, but the detection kit needs ultra-high detection sensitivity. Herein, the lowest detection concentration of different nucleic acid detection kits was evaluated and compared to provide direct evidence for the selection of kits for mixed sample detection or make recommendations for the selection of validation kit, which is of great significance for the prevention and control of the current epidemic and the discharge criteria of low viral load patients.

Transmission Routes Analysis of SARS-CoV-2: A Systematic Review and Case Report.

The global outbreak of SARS-CoV-2 spread rapidly throughout the world which transmitted among humans through various routes. Asymptomatic (carriers) and possible fecal-oral transmission, resulted into a large-scale spread. These issues pose great challenges to disease diagnosis and epidemic control. We obtained data on 29 cases of COVID-19 patients in Jinan, China, and reported the clinical data of asymptomatic patients confirmed with stool samples positive. Some patients with gastrointestinal infections are secondary to pulmonary infections, and during the patients' recovery period, the virus may still existin the patient's gastrointestinal tract over 7 days. We combined with epidemiological and clinical data of asymptomatic patients to analyze the possible routes of viral transmission and infection, including eyes-nose, hands-eyes, fecal-oral, and eyes-oral, et al., thus first presented the two-way transmission through eyes-oral. Through associating infection symptoms with the transmission routes of virus and the patient course of the disease, we expect to provide guidelines for clinical diagnosis and the basis for suppressing the spread of the virus and antiviral treatment.

Patients With LR-HPV Infection Have a Distinct Vaginal Microbiota in Comparison With Healthy Controls.

Condyloma acuminatum (CA) is a benign epithelium hyperplasia mainly caused by human papillomavirus (HPV), which is now the second most common viral sexually transmitted infection (STI) in China. In total, 90% of CA patients are caused by the low-risk HPV 6 and 11. Aside from low-risk HPV infection there are likely other factors within the local microenvironment that contribute to CA and there has been related research before. In this study, 62 vaginal specimens were analyzed using 16S rRNA gene sequencing. The diversity of the vaginal microbiota was higher and the composition was different with LR-HPV infection. While the relative abundance of dominant Firmicutes was lower, Actinobacteria, Proteobacteria, and Fusobacteria phyla were significantly higher; at the genus level Gardnerella, Bifidobacterium, Sneathia, Hydrogenophilus, Burkholderia, and Atopobium were higher. This study firstly confirmed a more accurate and comprehensive understanding of the relationship between low-risk HPV infection and vaginal microbiota, in order to provide a theoretical basis for further research on the occurrence and development of CA.

A method of oligochip for single nucleotide polymorphism genotyping in the promoter region of the interleukin-1 beta gene and its clinical application.

Single nucleotide polymorphisms (SNPs) can contribute to genetic predispositions or serve as genetic markers that are associated with complex diseases. So far, a few SNP arrays containing a limited number of SNPs have been used in routine genetic testing. This study described an oligochip-based method that genotypes two SNPs (-511 and -31) in the promoter region of the interleukin (IL)-1 beta gene. The sensitivity of this SNP genotyping method is derived from polymerase chain reaction (PCR)-amplified allele-specific primer-probes with a biotin label incorporated from the reverse primers. The amplified primer-probes can specifically hybridize with the oligonucleotides that are spotted on the oligochip. This oligochip-based method successfully discriminated the two biallelic SNPs with 9 different genotypes and all the genotyping results are in concordance with those from PCR restriction fragment length polymorphism (RFLP) analysis. Selective samples with various genotypes were also confirmed by direct sequencing. This method was applied in the genotyping of the patients with tuberculosis or gastric cancer and healthy controls. In the case control study, our genotyping data supported the reported association between gastric cancer and the genotypes of IL-1 beta -31 TT and -511 CC (p < 0.05). We also found that there is a significant difference of IL-1 beta -31 genotypes between 98 tuberculosis patients and healthy controls (p < 0.002). All of our results demonstrated that the oligochip can effectively and accurately identify SNP genotypes in the IL-1 beta promoter region.

Antitumor effect of a polysaccharide isolated from Phellinus pullus as an immunostimulant.

The antitumor function of fungal polysaccharides is a popular area of interest in the research field due to their high efficiency and low side effects. The main mechanism of fungal polysaccharides is immune enhancement. The polysaccharose (APS-3) was extracted from the fruit body of Phellinus pullus. The proliferation inhibition to mouse sarcoma 180 (S180) tumor cells was studied by the MTT method. Mice models of transplanted S180 tumor were established and treated with APS-3 to verify the antitumor activity in vivo. Natural killer (NK) and lymphokine-activated killer (LAK) cytotoxicities of the mice were evaluated by the lactate dehydrogenase method. APS-3 can significantly inhibit the proliferation of the S180 cells. Cells could be completely inhibited by 1.6 mg/ml APS-3 after 24 h treatment. After 18 days of treatment, the antitumor rate of the high-dose group was 85.47%. Histopathology detection showed that for the APS-3-treated mice, the tumor cells dissolved, and exhibited a large range of structureless necrotic areas. NK and LAK cytotoxicities of the APS-3 treated mice increased by 61.85 and 56.16%, respectively, compared with the normal control mice. APS-3 can be used as an antitumor agent by way of immune enhancement.

Development of a loop-mediated isothermal amplification method for rapid detection of streptococcal pyrogenic exotoxin B.

We developed a visual loop-mediated isothermal amplification (LAMP) technique to detect the streptococcal pyrogenic exotoxin B (speB) gene. Fifteen strains (from American Type Culture Collection or clinical isolates) were used to determine the specificity and sensitivity of the LAMP assay. Clinical samples were collected from 132 patients with suspected Streptococcus pyogenes (S. pyogenes) infection to verify the feasibility of the LAMP assay for detection of the speB gene. By using a set of five primers (a pair of outer primers, a pair of inner primers and one loop primer) targeting the speB gene, the amplification reaction was rapidly performed in a regular water bath under isothermal conditions at 63 °C for approximately 60 min. Only the two S. pyogenes strains showed positive results which were easily observed with the naked eye, and the other strains showed negative results. The detection limit of the LAMP assay was 0.01 ng/µl of template, showing higher sensitivity than conventional PCR (with a detection limit of 1.0 ng/µl). The detection rate of the speB gene in clinical samples was 71.21% and was consistent with the PCR results. The rapid detection of the speB gene by the LAMP assay is highly specific and sensitive, is simple to perform and cost-effective, and is expected to be a new reliable method for the rapid diagnosis of S. pyogenes infection, that is particularly suitable for rural or community hospitals in developing countries.

Downregulation of matrix metalloproteinases contributes to the inhibition of cell migration and invasion in HepG2 cells by sodium valproate.

Histone deacetylation levels are closely associated with the genesis and development of tumors. However, the anti-tumor effect and mechanism of class I histone deacetylase inhibitor sodium valproate (VPA) on hepatocellular carcinoma cells has not been demonstrated clearly. In the present study, HepG2 hepatocellular carcinoma cells were exposed to VPA, and the effects of VPA on the proliferation, apoptosis, metastasis and invasion of the cells were evaluated. The MTT method and colony assays were used to detect cell proliferation, and cell migration and Transwell invasion were also evaluated. In addition, the protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by flow cytometric analysis. The results indicated that VPA was able to inhibit proliferation and reverse the malignant phenotypes of hepatocellular carcinoma cells by inducing cell apoptosis. Furthermore, the colony formation and migration abilities of HepG2 cells were downregulated by VPA. Protein expression levels of MMP-2 and MMP-9 in HepG2 cells were also downregulated following VPA treatment, which contributed to suppression of the migration and invasion ability of HepG2 cells.

Diagnostic accuracy of fecal lactoferrin for inflammatory bowel disease: a meta-analysis.

OBJECTIVE: To do a systematic review using meta-analysis to assess the diagnostic accuracy of fecal lactoferrin (FL) in patients with inflammatory bowel disease (IBD). METHODS: We performed a literature review and systematically searched the Medline and EMBASE databases for eligible studies. The quality of the included studies was assessed using the QUADAS tool. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS: Seven studies, involving 1816 patients, met the inclusion criteria. In all studies, the pooled FL sensitivity and pooled specificity were 0.82 (95% confidence interval [CI]: 0.72, 0.89) and 0.95 (95% CI: 0.88, 0.98), respectively. The positive and negative likelihood ratios were 16.63 and 0.18, respectively. The area under the summary receiver-operating characteristic curve (SROC) was 0.95 (95% CI: 0.93, 0.97), and the diagnostic odds ratio was 90.04 (95% CI: 37.01, 219.02). The pooled FL sensitivity and specificity for Crohn's disease (CD) diagnosis (sensitivity =75%, specificity =100%) was not as good as it was for ulcerative colitis (UC) diagnosis (sensitivity =82%, specificity =100%). CONCLUSION: FL, as a noninvasive and screening marker, has a high specificity and a modest specificity during the diagnosis of suspected IBD.

Activation of the intrinsic apoptosis pathway contributes to the induction of apoptosis in hepatocellular carcinoma cells by valproic acid.

The level of histone deacetylation is closely associated with the genesis and development of tumors, but the antitumor effect and mechanism of the class I histone deacetylase inhibitor (HDACI) valproate acid sodium (VPA) on hepatocellular carcinoma cells has not been clearly demonstrated. In the present study, the antitumor effect and mechanism of VPA were measured in vitro. Firstly, it was found that, as an HDAC inhibitor, VPA could inhibit HDAC activity and HDAC1 gene expression in hepatocellular carcinoma cells and, as a result, an inhibition of cell proliferation was detected by MTT assay. Subsequently, the cell cycle and cell apoptosis profiles were analyzed using flow cytometry (FCM). The expression of the mRNA and protein of cyclins A, D1 and E and P21Waf/cip1 was measured by reverse transcription-polymerase chain reaction and FCM analysis to determine the molecular mechanism of VPA-induced cell cycle arrest. The activity and mRNA and protein expression of caspases 3, 8 and 9 were detected to determine the apoptotic pathway. Caspase expression was blocked by caspase inhibitors in order to observe whether the intrinsic or extrinsic pathway contributed to HepG2 cell apoptosis. The results revealed that the mRNA and protein expression of cyclins A and D1 was downregulated while the expression of P21Waf/cip1 was upregulated by VPA. The expression of cyclin E was only slightly affected by VPA. The mRNA and protein expression and activity of caspases 3 and 9 were upregulated by VPA. By contrast, inhibitors of caspases 3 and 9 could reverse cell apoptosis and there was no notable change in caspase 8 expression in any of these experiments. The intrinsic apoptosis pathway, but not the death receptor pathway, contributed to the induction of apoptosis in hepatocellular carcinoma cells. Furthermore, VPA could inhibit the proliferation of hepatocellular carcinoma cells by inducing G1 phase arrest and cell apoptosis. These effects were attributed to the change in the caspase level.

Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody for juvenile idiopathic arthritis.

OBJECTIVE: To estimate the diagnostic accuracy of the anti-CCP test in JIA and to evaluate factors associated with higher accuracy. METHODS: Two investigators performed an extensive search of the literature published between January 2000 and January 2014. The included articles were assessed by the Quality Assessment of Diagnostic Accuracy Studies tool. The meta-analysis was performed using a summary ROC (SROC) curve and a bivariate random-effect model to estimate sensitivity and specificity across studies. RESULTS: The bivariate meta-analysis yielded a pooled sensitivity and specificity of 10% (95% confidence interval (CI): 6.0%-15.0%) and 99.0% (95% CI: 98.0%-100.0%). The area under the SROC curve was 0.96. Sensitivity estimates were highly heterogeneous, which was partially explained by the higher sensitivity in the rheumatoid factor-positive polyarthritis (RF+ PA) subtype (48.0%; 95% CI: 31.0%-65.0%) than in the other subtypes (17.0%; 95% CI: 14.0%-20.0%) and the higher sensitivity of the Inova assay (17.0%; 95% CI: 14.0%-20.%%) than the other assays (0.05%; 95% CI: 2.0%-11.0%). CONCLUSIONS: Anti-CCP antibody test has a high specificity for the diagnosis of JIA. The sensitivity of this test is low and varies across populations but is higher in RF+ PA than in other JIA subtypes.