Publications by authors named "Lina Yi"

62 Publications

HOXD Antisense Growth-Associated Long Noncoding RNA Promotes Triple-Negative Breast Cancer Progression by Activating Wnt Signaling Pathway.

J Breast Cancer 2021 Jun 28;24(3):315-329. Epub 2021 Apr 28.

Department of Breast Surgery, Zhengxing Hospital, Zhangzhou, China.

Purpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options, which has a substantial deleterious effect on patients' lives. HOXD antisense growth-associated long noncoding RNA (lncRNA) (HAGLR) plays tumor-promoting roles in many cancers. In this study, we aimed to explore the role of HAGLR in TNBC.

Methods: Quantitative real-time polymerase chain reaction assays were used to examine the expression of RNAs. Functional experiments were conducted to test the biological behavior of TNBC cells. Moreover, MS2-RNA immunoprecipitation, luciferase reporter, and RNA pull-down assays were conducted to verify the binding relationship between HAGLR, microRNA-143-5p (miR-143-5p), and serine- and arginine-rich splicing factor 1 (SRSF1).

Results: HAGLR was found to be highly expressed in TNBC tissues and cells, and inhibiting HAGLR suppressed cell proliferation, migration, and invasion and promoted cell apoptosis in TNBC. Meanwhile, miR-93-5p was shown to bind to HAGLR and SRSF1. In addition, SRSF1 plays an oncogenic role in TNBC. Importantly, HAGLR could activate the Wnt signaling pathway by sponging miR-93-5p to upregulate SRSF1; thus, accelerating TNBC progression.

Conclusion: HAGLR could promote the progression of TNBC through the miR-93-5p/SRSF1 axis to activate the Wnt signaling pathway.
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http://dx.doi.org/10.4048/jbc.2021.24.e24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250102PMC
June 2021

MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study.

Front Oncol 2021 27;11:604801. Epub 2021 May 27.

Hunan University of Medicine, Huaihua, China.

Background: To know the expression of Mesenchymal-Epithelial Transition factor (MET) and Fatty Acid Synthase (FASN) in Triple Negative Breast Cancer (TNBC) patients, as well as its relationship with clinical pathological characteristic and prognosis.

Methods: we used immunohistochemistry staining to detect the expression of MET and FASN for those 218 TNBC patients, and analyze their relationship with the clinical pathological characteristic and prognosis.

Results: 130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition.

Conclusions: Our results indicated that MET and FASN showed good predictive ability for TNBC. Combined use of MET and FASN were recommended in order to make a more accurate prognosis for TNBC.
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http://dx.doi.org/10.3389/fonc.2021.604801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190390PMC
May 2021

Molecular surveillance of coxsackievirus A16 in southern China, 2008-2019.

Arch Virol 2021 Jun 1;166(6):1653-1659. Epub 2021 Apr 1.

Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangzhou, China.

A national surveillance system on hand, foot, and mouth disease (HFMD) was launched in 2008 in China. Since then, millions of HFMD cases have been reported each year, with enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) as the major causative pathogens. Long-term surveillance of viral infection rates and genetic changes is essential for understanding the disease epidemiology pattern. Here, we analyzed molecular surveillance data on CV-A16 covering a period of 12 years (2008-2019) in Guangdong, China, one of the regions reporting the largest number of HFMD cases. Full VP1 sequences of 456 strains were determined to examine the genetic diversity and changes in the distribution of CV-A16 variants. Our study revealed an irregular pattern of CV-A16 infections in Guangdong. Different from the cyclic epidemics observed in some Asia-Pacific regions, there was a continuously high CV-A16 infection rate from 2008 to 2014, and after a period of lower epidemic activity in 2015-2017, an upsurge of CV-A16 infection was observed in 2018-2019. Cocirculation of subgenotypes B1a and B1b was observed, but while subgenotype B1a was predominant from 2008 to 2012, it appears to have been replaced by B1b, which has circulated as the predominant subgenotype since 2013. Phylogenetic analysis showed that most of the circulating CV-A16 strains are endemic, with occasional transmission between neighboring regions. The re-emergence of B1a in 2016-2019 in Guangdong was likely the result of introduction(s) from Southeast Asia. These results highlight the importance of continuous molecular surveillance from different areas, which will improve our understanding of the origin of the epidemic and facilitate the development of strategies for HFMD disease control.
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http://dx.doi.org/10.1007/s00705-021-05052-8DOI Listing
June 2021

Capturing noroviruses circulating in the population: sewage surveillance in Guangdong, China (2013-2018).

Water Res 2021 May 1;196:116990. Epub 2021 Mar 1.

Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China. Electronic address:

Noroviruses (NoVs) are the leading cause of acute gastroenteritis (AGE) outbreaks. Since 2014, novel genetic variants of NoV have been continuously identified and have caused a sharp increase in the number of AGE outbreaks. The specific geographical distribution and expanding genetic diversity of NoV has posed a challenge to conventional surveillance. Here, we describe the long-term dynamic correlation between NoV distribution in sewage and in the local population through the molecular surveillance of NoV in Guangdong, 2013-2018. The relative viral loads of the GI and GII genotypes in sewage were calculated through RT-PCR. A high-throughput sequencing method and operational taxonomic unit (OTU) clustering pipeline were developed to illustrate the abundances of different genotypes and genetic variants in sewage. Our results showed that the NoV viral loads and the emergence of new variants in sewage were closely associated with NoV outbreak risks in the population. Compared with the outbreaks surveillance, the dominance of the newly emerged variants, GII.P17-GII.17 and GII.P16-GII.2, could be detected one or two months ahead in sewage of a hub city. In addition, the dynamics of pre-epidemic variants, which were rarely detected in clinics, could be captured through sewage surveillance, thus improving our understanding of the origin and evolution of these novel epidemic variants. Our data highlight that sewage surveillance could provide nearly real-time and high-throughput data on NoV circulation in the community. With the advances in sequencing techniques, the sewage surveillance system could also be extended to other related infectious diseases.
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http://dx.doi.org/10.1016/j.watres.2021.116990DOI Listing
May 2021

Study on the treatment of oily sludge in oil fields with lipopeptide/sophorolipid complex bio-surfactant.

Ecotoxicol Environ Saf 2021 Apr 30;212:111964. Epub 2021 Jan 30.

PetroChina Research Institute of Petroleum Exploration and Development, China.

A systematic study had been carried out to get insight into the micellar behavior of anionic lipopeptide (LT) and nonionic sophorolipid (SL) in their different mass ratio mixed state using the technique of tensiometry. The models proposed by Clint, Rubingh and Gibbs et al. had been employed to interpret the formation of mixed micelles and found out synergism. The obtained experimental critical micelle concentrations (CMC) were lower than the ideal CMCs, indicating negative deviation from ideal behavior for all multi-component mixed micelles formation. A suited binary bio-surfactant mixing system was selected as the washing agents to treat the oily sludge produced from Huabei oilfield by the thermal bio-surfactant washing method. The results showed that in case of the mass ratios of 8:2 the CMC was dramatically decreased and synergism was the strongest in LT and SL bi mixed surfactant systems. The studied binary mixed bio-surfactant system showed higher washing efficiency for oily sludge than single surfactant system. In addition, the washing power of binary mixed bio-surfactants towards oily sludge was the best at below washing conditions: (a) the concentration of the mixed system (100 mg/L), (b) temperature (55 ℃), (c) ratio of sludge/liquid (1:3), (d) washing time (3 h), and (e) stirring speed (300 rpm). Certainly, the washing abilities of the selected surfactants not only depend on their mixing ratio and washing conditions but also associate with microstructure and mineral components of oily sludge.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111964DOI Listing
April 2021

Emergence of a non vaccine-cognate enterovirus A71 genotype C1 in mainland China.

J Infect 2021 03 26;82(3):407-413. Epub 2020 Dec 26.

Center for Disease Control and Prevention of Guangdong Province, Guangzhou, Guangdong, China. Electronic address:

Background: EV-A71 is a common causative agent of hand foot and mouth disease. In mainland China, EV-A71 subgenotype C4 has been the sole circulating genotype since 2008, and was used in the production of multiple licensed vaccines. Here, we report the first detection EV-A71 C1 strains in China.

Methods: Full genomic sequence were obtained. The origin of the EV-A71 C1 strains were tracked down by Bayesian inferences. Recombination was analyzed using Simplot program. And the antigenicity were tested using the microneutralization test.

Results: The C1-GD2019 shared high identity with the C1-like lineage recently identified in Europe and was introduced into Guangdong in 2018-2019. Close genetic relatedness between the C1-GD2019 and Europe C1-like strains were observed except for the 3D-3'UTR region. The late showed high similarity with CVA genomes. Antigenic variance was found. The C1-GD2019 could not be effectively neutralized by EV-A71 C4a neutralizing antibody positive samples.

Conclusion: This is the first report of EV-A71 subgenotype C1 isolated in China. It is a recombinant strain originating from C1-like strains recently identified in Europe and CVA strains. The different antigenicity between the C1 strains and C4a vaccine strains highlighted the importance on closely monitoring the EV-A71 C1 strains in China.
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http://dx.doi.org/10.1016/j.jinf.2020.12.020DOI Listing
March 2021

Promotive effect of Talin-1 protein on gastric cancer progression through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signaling axis.

J Clin Lab Anal 2020 Dec 20;34(12):e23555. Epub 2020 Sep 20.

Department of Radiology, The Second Affiliated Hospital of Nantong University, Nantong, China.

Objective: Our research group was aim to explore the molecular mechanism of Talin-1 protein affecting gastric cancer progression through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signal axis.

Methods: 12 cases of patients with gastric cancer in this hospital from 2018 to 2019 were collected. Immunohistochemistry assay and Western blotting were used to detect the expression of Talin-1, PXN, E-Cadherin, CAPN2, MAPK1 protein in gastric cancer tissue. Cell migration and invasion were measured by Transwell.

Results: The results showed that the expression levels of protein Talin-1, PXN and MAPK1 in gastric cancer tissues were significantly higher than that in normal tissue. The number of cell adhesion in the model group was significantly lower than that in the normal group. However, the cell adhesion number in ov-TLN1 was the highest. Transwell results showed that TLN1 could accelerate the migration and invasion abilities of gastric cancer MKN-45 cells. Moreover, Western blotting showed that protein Talin-1, PXN, E-Cadherin, CAPN2, MAPK1 in model group all increased compared with normal group.

Conclusion: It indicated that talin-1 protein influenced the development of gastric cancer through PTK2-PXN-VCL-E-Cadherin-CAPN2-MAPK1 signal axis.
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http://dx.doi.org/10.1002/jcla.23555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755796PMC
December 2020

Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR.

EBioMedicine 2020 Sep 24;59:102960. Epub 2020 Aug 24.

Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China. Electronic address:

Background: Some COVID-19 cases test positive again for SARS-CoV-2 RNA following negative test results and discharge, raising questions about the meaning of virus detection. Better characterization of re-positive cases is urgently needed.

Methods: Clinical data were obtained through Guangdong's COVID-19 surveillance network. Neutralization antibody titre was determined using microneutralization assays. Potential infectivity of clinical samples was evaluated by cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing.

Findings: Among 619 discharged COVID-19 cases, 87 re-tested as SARS-CoV-2 positive in circumstances of social isolation. All re-positive cases had mild or moderate symptoms at initial diagnosis and were younger on average (median, 28). Re-positive cases (n = 59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n = 218) tested here. No infectious strain could be obtained by culture and no full-length viral genomes could be sequenced from re-positive cases.

Interpretation: Re-positive SARS-CoV-2 cases do not appear to be caused by active reinfection and were identified in ~14% of discharged cases. A robust NAb response and potential virus genome degradation were detected in almost all re-positive cases, suggesting a substantially lower transmission risk, especially through respiratory routes.
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http://dx.doi.org/10.1016/j.ebiom.2020.102960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444471PMC
September 2020

Adenovirus infection in children hospitalized with pneumonia in Guangzhou, China.

Influenza Other Respir Viruses 2021 Jan 5;15(1):27-33. Epub 2020 Aug 5.

Guangdong Provincial Center for Diseases Control and prevention, Guangzhou, China.

Background: HAdV infection can cause a variety of diseases. Although infections with HAdVs often are mild, life-threatening respiratory disease can occur. Pneumonia is one of the more serious types of HAdV-induced respiratory disease in children. In this study, we determined the prevalence and genotype of HAdVs among children hospitalized with pneumonia in Guangzhou, China.

Methods: Nasopharyngeal swabs (NPSs) were collected from children hospitalized with pneumonia in Guangzhou, China, from January 2013 to June 2019. HAdVs were detected by real-time polymerase chain reaction assay, and hexon, fiber, and penton gene were amplified and used for phylogenetic analysis. Epidemiological data were analyzed using SPSS16.0 software.

Results And Conclusions: A total of 1778 children hospitalized with pneumonia were enrolled. The overall HAdV detection rate was 3.26%. And the yearly detection rate varied from around 2.5% in 2013-2017 to around 6% in 2018-2019. Children >5 years had the highest HAdV infection rate. 92.86% of HAdV sequences obtained in this study were belonged to species B, and no recombination was observed. HAdV-B7 and HAdV-B3 were the common types detected in the study period, with the predominant HAdV genotype shifted from HAdV-B3 in 2015-2016 to HAdV-B7 in 2017-2018. The discrepancies in HAdV detection rates in different study period and changes of HAdV predominant types over time highlighted the importance of continued surveillance.
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http://dx.doi.org/10.1111/irv.12782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767961PMC
January 2021

Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2.

J Virol 2020 08 17;94(17). Epub 2020 Aug 17.

Guangdong Provincial Institution of Public Health, Guangzhou, China

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in December 2019. Notable features that make SARS-CoV-2 distinct from most other previously identified betacoronaviruses include a receptor binding domain and a unique insertion of 12 nucleotides or 4 amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells; however, the deletion of QTQTN may restrict late-phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and 12 of 24 -isolated viruses, while the deletion of NSPRRAR was identified in 3 -isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection and ; (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage; and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here. The spike protein determines the infectivity and host range of coronaviruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has two unique features in its spike protein, the receptor binding domain and an insertion of 12 nucleotides at the S1/S2 boundary resulting in a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN), and we investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR sequence and the flanking QTQTN sequence are not fixed thus, there appears to be distinct selection pressures on SARS-CoV-2 sequences and Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.
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http://dx.doi.org/10.1128/JVI.00790-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431800PMC
August 2020

Tracking echovirus eleven outbreaks in Guangdong, China: a metatranscriptomic, phylogenetic, and epidemiological study.

Virus Evol 2020 Jan 10;6(1):veaa029. Epub 2020 May 10.

Guangdong Provincial Center for Disease Control and Prevention, No. 160, Qunxian Road, Panyu District, Guangzhou, China.

In April 2019, a suspect cluster of enterovirus cases was reported in a neonatology department in Guangdong, China, resulting in five deaths. We aimed to investigate the pathogen profiles in fatal cases, the circulation and transmission pattern of the viruses by combining metatranscriptomic, phylogenetic, and epidemiological analyses. Metatranscriptomic sequencing was used to characterize the enteroviruses. Clinical and environmental surveillance in the local population was performed to understand the prevalence and genetic diversity of the viruses in the local population. The possible source(s), evolution, transmission, and recombination of the viruses were investigated by incorporating genomes from the current outbreak, from local retrospective surveillance, and from public databases. Metatranscriptomic analysis identified Echovirus 11 (E11) in three fatal cases. Seroprevalence of neutralization antibody to E11 was 35 to 44 per cent in 3-15 age groups of general population, and the viruses were associated with various clinical symptoms. From the viral phylogeny, nosocomial transmissions were identified and all E11 2019 outbreak strains were closely related with E11 strains circulating in local population 2017-19. Frequent recombination occurred among the 2019 Guangdong E11 outbreak strains and various genotypes in enterovirus B species. This study provides an example of combining advanced genetic technology and epidemiological surveillance in pathogen diagnosis, source(s), and transmission tracing during an infectious disease outbreak. The result highlights the hidden E11 circulation and the risk of viral transmission and infection in the young age population in China. Frequent recombination between Guangdong-like strains and other enterovirus genotypes also implies the prevalence of these emerging E11 strains.
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http://dx.doi.org/10.1093/ve/veaa029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211399PMC
January 2020

Genomic Epidemiology of SARS-CoV-2 in Guangdong Province, China.

Cell 2020 05 30;181(5):997-1003.e9. Epub 2020 Apr 30.

Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.
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http://dx.doi.org/10.1016/j.cell.2020.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192124PMC
May 2020

Trim14 promotes autophagy and chemotherapy resistance of gastric cancer cells by regulating AMPK/mTOR pathway.

Drug Dev Res 2020 08 25;81(5):544-550. Epub 2020 Feb 25.

Department of Pathology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.

Objective: To study the relationship between TRIM14 expression and chemotherapy resistance of gastric cancer (GC) cells.

Methods: The expression of TRIM14 in 5-fluorouracil (5-FU)- and oxaliplation (L-OHP)-resistant GC tissues and cells were determined by qRT-PCR and western blotting. PcDNA3.1-TRIM14 and shRNA-TRIM14 vector were transfected to 5-FU-resistant GC cells (SGC7901/5-FU), and the proliferation and apoptosis of cells were measured. Animal experiments on 5-FU-resistant GC mice were performed to study the effect of TRIM14 expression on tumor size and weight, GC cell migration, and proliferation. pcDNA3.1-MK-3903 plasmid was transfected to SGC7901/5-FU cells with TRIM14 silence. The cell proliferation and apoptosis were determined. The protein expressions of Trim14, LC3, and BECLIN1 were measured by western blotting.

Results: TRIM14 was significantly upregulated in 5-FU- and L-OHP-resistant GC tissues and cells. The overexpression of TRIM14 promoted the proliferation and autophagy of SGC7901/5-FU cells, and inhibited the apoptosis. Moreover, in vivo experiment verified that the silence of TRIM14 reduced the tumor size and weight, and inhibited the migration and proliferation of GC cells in 5-FU-resistant GC mice. The overexpression of MK-3903 reversed the inhibiting role of TRIM14 knockout on the proliferation and autophagy of SGC7901/5-FU cells.

Conclusion: TRIM14 promoted chemotherapy resistance of GC cells by regulating AMPK/mTOR pathway, and may be a new biomarker for treating GC.
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http://dx.doi.org/10.1002/ddr.21650DOI Listing
August 2020

Pelvic reconstructive surgery combined with substitute implantation in the treatment of elderly patients with pelvic organ prolapse.

Minerva Chir 2020 02 30;75(1):60-63. Epub 2019 Sep 30.

Department of Gynecology, Chifeng Municipal Hospital, Chifeng, China -

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http://dx.doi.org/10.23736/S0026-4733.19.08166-5DOI Listing
February 2020

Epidemiology, evolution and transmission of human metapneumovirus in Guangzhou China, 2013-2017.

Sci Rep 2019 10 1;9(1):14022. Epub 2019 Oct 1.

Guangdong Provincial Center for Disease Control and Prevention, No. 160, Qunxian Road, Panyu District, Guangzhou, China.

Human metapneumovirus (hMPV), first identified in 2001, is a major viral respiratory pathogen that worldwide reported. Fundamental questions concerning the dynamics of viral evolution and transmission at both regional and global scales remain unanswered. In this study, we obtained 32 G gene and 51 F gene sequences of hMPV in Guangzhou, China in 2013-2017. Temporal and spatial phylogenetic analyses were undertaken by incorporating publicly available hMPV G gene (978) and F gene (767) sequences. The phylogenetic results show different global distribution patterns of hMPV before 1990, 1990-2005, and 2006-2017. A sharply increasing hMPV positive rate (11%) was detected in Guangzhou 2017, mainly caused by the B1 lineage of hMPV. A close phylogenetic relation was observed between hMPV strains from China and Japan, suggesting frequent hMPV transmissions between these regions. These results provide new insights into hMPV evolution, transmission, and spatial distribution and highlight Asia as a new epicenter for viral transmission and novel variant seeding after the year 2005. Conducting molecular surveillance of hMPV in Asian countries is critical for understanding the global circulation of hMPV and future vaccine design.
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http://dx.doi.org/10.1038/s41598-019-50340-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773679PMC
October 2019

Co-circulation and persistence of multiple A/H3N2 influenza variants in China.

Emerg Microbes Infect 2019 ;8(1):1157-1167

a Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing , People's Republic of China.

The spread of influenza A/H3N2 variants possessing the hemagglutinin 121 K mutation and the unexpectedly high incidence of influenza in the 2017-2018 northern hemisphere influenza season have raised serious concerns about the next pandemic. We summarized the national surveillance data of seasonal influenza in China and identified marked differences in influenza epidemics between northern and southern China, particularly the predominating subtype and the presence of an additional summer peak in southern China. Notably, a minor spring peak of influenza caused by a different virus subtype was also observed. We also revealed that the 3C.2a lineage was dominant from the summer of 2015 to the end of the 2015-2016 peak season in China, after which the 3C.2a2 lineage predominated despite the importation and co-circulation of the 121 K variants of 3C.2a1 and 3C.2a3 lineages at the global level. Finally, an analysis based on genetic distances revealed a delay in A/H3N2 vaccine strain update. Overall, our results highlight the complicated circulation pattern of seasonal influenza in China and the necessity for a timely vaccine strain update worldwide.
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http://dx.doi.org/10.1080/22221751.2019.1648183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713139PMC
December 2019

A human infection with a novel reassortant H3N2 swine virus in China.

J Infect 2019 08 1;79(2):174-187. Epub 2019 May 1.

Guangdong Provincial Center for Disease Control and Prevention, No. 160, Qunxian Road, Panyu District, Guangzhou, Guangdong, China; Southern Medical University, No. 1838, Shatai Road, Baiyun District, Guangzhou, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2019.04.015DOI Listing
August 2019

Hsp27 Responds to and Facilitates Enterovirus A71 Replication by Enhancing Viral Internal Ribosome Entry Site-Mediated Translation.

J Virol 2019 05 17;93(9). Epub 2019 Apr 17.

Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong

Enterovirus 71 (EV-A71) is a human pathogen that causes hand, foot, and mouth disease (HFMD) and fatal neurological diseases, and no effective treatment is available. Characterization of key host factors is important for understanding its pathogenesis and developing antiviral drugs. Here we report that Hsp27 is one of the most upregulated proteins in response to EV-A71 infection, as revealed by two-dimensional gel electrophoresis-based proteomics studies. Depletion of Hsp27 by small interfering RNA or CRISPR/Cas9-mediated knockout significantly inhibited viral replication, protein expression, and reproduction, while restoration of Hsp27 restored such virus activities. Furthermore, we show that Hsp27 plays a crucial role in regulating viral internal ribosome entry site (IRES) activities by two different mechanisms. Hsp27 markedly promoted 2A-mediated eukaryotic initiation factor 4G cleavage, an important process for selecting and initiating IRES-mediated translation. hnRNP A1 is a key IRES -acting factor (ITAF) for enhancing IRES-mediated translation. Surprisingly, knockout of Hsp27 differentially blocked hnRNP A1 but not FBP1 translocation from the nucleus to the cytoplasm and therefore abolished the hnRNP A1 interaction with IRES. Most importantly, the Hsp27 inhibitor 1,3,5-trihydroxy-13,13-dimethyl-2-pyran [7,6-] xanthone (TDP), a compound isolated from a traditional Chinese herb, significantly protected against cytopathic effects and inhibited EV-A71 infection. Collectively, our results demonstrate new functions of Hsp27 in facilitating virus infection and provide novel options for combating EV-A71 infection by targeting Hsp27. Outbreaks of infections with EV-A71, which causes hand, foot, and mouth disease, severe neurological disorders, and even death, have been repeatedly reported worldwide in recent decades and are a great public health problem for which no approved treatments are available. We show that Hsp27, a heat shock protein, supports EV-A71 infection in two distinct ways to promote viral IRES-dependent translation. A small-molecule Hsp27 inhibitor isolated from a traditional Chinese medicinal herb effectively reduces virus yields. Together, our findings demonstrate that Hsp27 plays an important role in EV-A71 infection and may serve as an antiviral target.
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http://dx.doi.org/10.1128/JVI.02322-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475798PMC
May 2019

Molecular Evolution, Diversity, and Adaptation of Influenza A(H7N9) Viruses in China.

Emerg Infect Dis 2018 10;24(10):1795-1805

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016-17 raises concerns about the epizootic potential of these viruses. We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015-2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity. Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution.
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http://dx.doi.org/10.3201/eid2410.171063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154164PMC
October 2018

Fecal bacterial diversity of wild Sichuan snub-nosed monkeys (Rhinopithecus roxellana).

Am J Primatol 2018 04 10;80(4):e22753. Epub 2018 Apr 10.

College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.

The gastrointestinal tract of primates harbors a complex microbial community, playing an essential role in the degradation of otherwise indigestible structural carbohydrates. The phylogenetic and functional diversity of the bacterial community in the feces as a surrogate for the gastrointestinal tract of wild Sichuan snub-nosed monkeys (Rhinopithecus roxellana, N = 6) was characterized based on sequence analysis of 16S rRNA genes. A sex comparison was conducted, with a prior hypothesis that the abundances of the bacterial taxa and/or functional categories associated with energy and nutrient metabolism would be higher in adult females (N = 3) due to the higher reproductive costs compared to adult males (N = 3). Ten phyla were identified in all samples, among which Bacteroidetes and Firmicutes were the predominant. Included in the above two phyla, the members of Prevotellaceae (Prevotella in particular) and Ruminococcaceae were highly abundant, which are common bacteria in the gastrointestinal tract of primates and can degrade various structural carbohydrates such as cellulose, hemicellulose, and pectin. This functionality was in line with the high abundances of the metagenomes associated with carbohydrate metabolism. Consistent with our hypothesis, the abundances of the metagenomes associated with energy metabolism, folding/sorting and degradation, glycan biosynthesis and metabolism, and metabolism of amino acids were higher in adult females relative to adult males. Sex differences were also detected in the bacterial community structure, although no sex differences in the proportions of any bacterial taxa were found likely due to the small sample size. These results suggested that gastrointestinal bacterial communities may aid adult females in increasing energy and nutrition utilization efficiencies compared to adult males. Fecal bacterial communities were found to be more similar between individuals in adult females than in adult males. Our study presented the first examination of the fecal bacterial diversity of a little-studied, endangered foregut fermenter.
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http://dx.doi.org/10.1002/ajp.22753DOI Listing
April 2018

Expression analysis of E-cad and vascular endothelial growth factor in triple-negative breast cancer patients of different ethnic groups in western China.

Medicine (Baltimore) 2017 Oct;96(42):e8155

Department of Breast Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, P.R. China.

The aim of this article is to investigate the expression of E-cadherin (E-cad) and vascular endothelial growth factor (VEGF) in triple-negative breast cancer (TNBC) of Han and Uygur women patients in western China, and their relationship with clinical features of TNBC.Totally, 172 cases of Han TNBC patients and 79 cases of Uighur TNBC patients were enrolled. The expressions of E-cad and VEGF were detected with immunohistochemistry. The correlation of E-cad and VEGF expression with lymph node metastasis, TNM stage, and histological grade were analyzed. The 5-year disease-free survival rate of the 2 groups was also evaluated.There was no significant difference in the 5-year disease-free survival rate (P > .05) and the expression of E-cad between the 2 groups. The positive rate of VEGF in Han was significantly lower than that in Uygur (P < .05). The expression of E-cad was negatively correlated with lymph node metastasis, TNM stage, and histological grade (-1≤r < 1, P < .05). However, the expression of VEGF was positively correlated with lymph node metastasis and TNM staging (0 < r < 1, P < 0.05), but not with histological grading.The expression of E-cad and VEGF and their relationship with clinical features of TNBC suggest that Uygur TNBC patients might have different prognostic factors as compared with Han patients.
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http://dx.doi.org/10.1097/MD.0000000000008155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662364PMC
October 2017

Laboratory evaluation of the Anyplex™ II MTB/MDR and MTB/XDR tests based on multiplex real-time PCR and melting-temperature analysis to identify Mycobacterium tuberculosis and drug resistance.

Diagn Microbiol Infect Dis 2017 Dec 25;89(4):276-281. Epub 2017 Aug 25.

Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (JATA), Tokyo, Japan; Department of Basic Mycobacteriology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

We evaluated the performance of two multiplex, real-time PCR tests (Anyplex II MTB/MDR and MTB/XDR; Seegene, Seoul, Korea), designed to detect the Mycobacterium tuberculosis complex (MTC) and drug-resistance mutations associated with isoniazid, rifampicin, fluoroquinolones, and second-line injectable drugs. We analyzed 122 clinical isolates with the Anyplex II MTB/MDR test, 68 of which were also tested with the Anyplex II MTB/XDR test. The Anyplex II MTB/MDR and MTB/XDR tests showed the following respective sensitivities and specificities: 68.8% and 100% for detecting isoniazid resistance, 93.8% and 100% for rifampicin, 82.8% and 100% for levofloxacin, 75.0% and 100% for kanamycin, and 92.6% and 100% for MTC identification. These kits correctly identified 61.8% of multi-drug resistant M. tuberculosis isolates and 64.7% of extensively drug-resistant M. tuberculosis isolates, and enabled semi-automatic detection of drug-resistant MTC in 3 hours. The Anyplex II kits could be useful as rule-in tests for detecting MTC and drug resistance.
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http://dx.doi.org/10.1016/j.diagmicrobio.2017.08.016DOI Listing
December 2017

A45 Family clusters of avian influenza A H7N9 infection in Guangdong Province, China.

Virus Evol 2017 Mar 5;3(Suppl 1). Epub 2017 Mar 5.

Guangdong Provincial Center for Disease Control and Prevention, No. 160, Qunxian Road, Panyu District, Guangzhou, China.

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http://dx.doi.org/10.1093/ve/vew036.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565925PMC
March 2017

activity of sitafloxacin against with mutations isolated in Japan.

J Med Microbiol 2017 Jun;66(6):770-776

Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Japan.

Sitafloxacin (SFX) is a new fluoroquinolone (FQ) that has shown a strong bactericidal effect against (Mtb) . However, data on SFX efficacy against Mtb with mutations and its epidemiological cut-off (ECOFF) value remain limited. Therefore, we evaluated and compared the activity of SFX against -mutant Mtb to that of moxifloxacin (MFX), levofloxacin (LFX) and ciprofloxacin (CFX), and determined the ECOFF for SFX. A total of 109 clinical Mtb isolates, including 73 multidrug-resistant (MDR) isolates, were subjected to minimum inhibitory concentration (MIC) analysis in oleic-albumin-dextrose-catalase (OADC)-supplemented Middlebrook 7H9 medium. Our results showed that SFX had lower cumulative MIC than MFX, LFX and CFX. Furthermore, we performed direct DNA sequencing of the quinolone-resistance-determining regions (QRDRs). We identified the following mutations: D94G, D94A, A90V, D94H, D94N and G88A in gyrA; and A543V, A543T, E540D, R485C, D500A, I552S and D577A in . Based on our results, an ECOFF of 0.125 µg ml was proposed for SFX. With this ECOFF, 15 % of LFX-resistant isolates with MIC ≥2 µg ml were susceptible to SFX. SFX had the lowest cumulative MIC and a relatively low ECOFF value against Mtb, indicating that SFX was not only more effective against -mutant isolates, but also MDR isolates in Japan.
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http://dx.doi.org/10.1099/jmm.0.000493DOI Listing
June 2017

A cluster of adenovirus type B55 infection in a neurosurgical inpatient department of a general hospital in Guangdong, China.

Influenza Other Respir Viruses 2017 07 26;11(4):328-336. Epub 2017 Jun 26.

Center for Disease Control and Prevention of Guangdong Province, Guangzhou, China.

Background: Human adenovirus type 55 is a re-emerging human respiratory pathogen that is associated with several respiratory infections outbreaks in military and school populations. In this study, we describe the first HAdV55-associated hospital outbreak documented in Guangdong, China.

Methods: Active surveillance was conducted in the involved neurosurgical inpatient department. All staff and patients in the involved neurosurgical department were surveyed for any symptoms of fever (≥38°C) and enlarged tonsils during the outbreak period. Throat swabs and demographic information were collected for all cases. For each specimen, assays for common respiratory viruses were performed using one-step reverse transcription-polymerase chain reaction. HAdV-positive samples were inoculated onto Hep-2 cells for isolation. Hexon genes, fiber genes, penton genes, and whole genomes were sequenced. A phylogenetic tree was constructed.

Results And Conclusions: Forty-three cases, including 24 laboratory-confirmed cases and 19 possible cases, were identified. Nurses had the highest attack rate of infection, with a rate of 36.4%. The attack rate for doctors and inpatients was 20.0% and 16.7%, respectively. HAdV55 was the sole pathogen identified during this outbreak. The hexon, fiber, and penton genes from seven isolated HAdV55 stains were sequenced. All these genes showed 100% homology and fell into the HAdV55 [P14H11F14] cluster, indicating that HAdV55 was the single viral strain for the outbreak. While not conclusive, the epidemic investigation revealed that the outbreak was introduced by nurses from sources outside the hospital. It was likely that a transmission from staff to inpatients had occurred.
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http://dx.doi.org/10.1111/irv.12457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485872PMC
July 2017

Disulfide Bond Formation and N-Glycosylation Modulate Protein-Protein Interactions in GPI-Transamidase (GPIT).

Sci Rep 2017 04 4;8:45912. Epub 2017 Apr 4.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Glycosylphosphatidylinositol (GPI) transamidase (GPIT), the enzyme that attaches GPI anchors to proteins as they enter the lumen of the endoplasmic reticulum, is a membrane-bound hetero-pentameric complex consisting of Gpi8, Gpi16, Gaa1, Gpi17 and Gab1. Here, we expressed and purified the luminal domain of Saccharomyces cerevisiae (S. cerevisiae) Gpi8 using different expression systems, and examined its interaction with insect cell expressed luminal domain of S. cerevisiae Gpi16. We found that the N-terminal caspase-like domain of Gpi8 forms a disulfide-linked dimer, which is strengthened by N-glycosylation. The non-core domain of Gpi8 following the caspase-like domain inhibits this dimerization. In contrast to the previously reported disulfide linkage between Gpi8 and Gpi16 in human and trypanosome GPIT, our data show that the luminal domains of S. cerevisiae Gpi8 and S. cerevisiae Gpi16 do not interact directly, nor do they form a disulfide bond in the intact S. cerevisiae GPIT. Our data suggest that subunit interactions within the GPIT complex from different species may vary, a feature that should be taken into account in future structural and functional studies.
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http://dx.doi.org/10.1038/srep45912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379210PMC
April 2017

A cluster of coxsackievirus A21 associated acute respiratory illness: the evidence of efficient transmission of CVA21.

Arch Virol 2017 Apr 26;162(4):1057-1059. Epub 2016 Dec 26.

Guangdong Provincial Centre for Disease Control and Prevention, Guangdong, 514300, China.

In March 2016, a cluster of unexplained respiratory illnesses was reported by the acute respiratory infections (ARI) surveillance system of Guangdong Province, China. Twenty-three high school students and one teacher from the four neighboring classes were admitted to a hospital. CVA21 was found in eight of fourteen patients. Phylogenetic analysis suggested that the CVA21 outbreak was most likely caused by transmission of the virus from person to person. This is the first report of an ARI outbreak caused by CVA21, which suggests that CVA21 has the potential to be transmitted efficiently from person to person and should be closely monitored by clinicians and public health agencies.
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http://dx.doi.org/10.1007/s00705-016-3201-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087265PMC
April 2017

Effect of Live Poultry Market Interventions on Influenza A(H7N9) Virus, Guangdong, China.

Emerg Infect Dis 2016 12;22(12):2104-2112

Since March 2013, three waves of human infection with avian influenza A(H7N9) virus have been detected in China. To investigate virus transmission within and across epidemic waves, we used surveillance data and whole-genome analysis of viruses sampled in Guangdong during 2013-2015. We observed a geographic shift of human A(H7N9) infections from the second to the third waves. Live poultry market interventions were undertaken in epicenter cities; however, spatial phylogenetic analysis indicated that the third-wave outbreaks in central Guangdong most likely resulted from local virus persistence rather than introduction from elsewhere. Although the number of clinical cases in humans declined by 35% from the second to the third waves, the genetic diversity of third-wave viruses in Guangdong increased. Our results highlight the epidemic risk to a region reporting comparatively few A(H7N9) cases. Moreover, our results suggest that live-poultry market interventions cannot completely halt A(H7N9) virus persistence and dissemination.
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http://dx.doi.org/10.3201/eid2212.160450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189139PMC
December 2016

Evolution and Transmission of Respiratory Syncytial Group A (RSV-A) Viruses in Guangdong, China 2008-2015.

Front Microbiol 2016 15;7:1263. Epub 2016 Aug 15.

Guangdong Provincial Center for Disease Control and PreventionGuangzhou, China; Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and PreventionGuangzhou, China; Department of Zoology, University of OxfordOxford, UK.

Respiratory syncytial viruses (RSVs) including subgroups A (RSV-A) and B (RSV-B) are an important cause of acute respiratory tract infections worldwide. RSV-A include major epidemic strains. Fundamental questions concerning the evolution, persistence and transmission of RSV-A are critical for disease control and prevention, yet remain unanswered. In this study, we generated 64 complete G gene sequences of RSV-A strains collected between 2008 and 2015 in Guangdong, China. Phylogenetic analysis was undertaken by incorporating 572 publicly available RSV-A sequences. Current data indicate that genotypes GA1, GA4, and GA5 are endemic with limited epidemic activity. In contrast, the GA2 genotype which likely originated in 1980 has spread rapidly and caused epidemics worldwide. By analyzing GA2 genotype sequences across epidemic seasons within Guangdong, we find that RSV-A epidemics in Guangdong are caused by a combination of virus importation and local persistence, although the magnitude of the latter is likely overestimated due to infrequent sampling in other regions. Our results provide new insights into RSV-A evolution and transmission at global and local scales and highlights the rapid and wide spread of genotype GA2 compared to other genotypes. In order to control RSV transmission and outbreak, both local persistence and external introduction should be taken into account when designing optimal strategies.
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http://dx.doi.org/10.3389/fmicb.2016.01263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983572PMC
August 2016

Evaluation of QuantiFERON-TB Gold Plus for Detection of Mycobacterium tuberculosis infection in Japan.

Sci Rep 2016 07 29;6:30617. Epub 2016 Jul 29.

Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Japan.

Performance of interferon-γ (IFN-γ) release assays still needs to be improved. The data on the performance of QuantiFERON-TB Gold Plus (QFT-Plus), a new-generation of QFT assay are limited. This study evaluated the diagnostic performance of QFT-Plus, and compared to that of QuantiFERON-TB Gold In-Tube (QFT-GIT). Blood samples were collected from 162 bacteriologically confirmed tuberculosis (TB) patients and 212 Mycobacterium tuberculosis-uninfected volunteers; these samples were then tested with QFT-GIT and QFT-Plus. The IFN-γ concentration of QFT-Plus was lower than that of QFT-GIT in TB patients (p < 0.001). Receiver operating characteristic curves were compared between QFT-GIT and QFT-Plus. Both assays showed area under the curve values over 0.99 without significant difference. Using the conventional cut-off (0.35 IU/mL) for QFT-GIT, QFT-Plus had a lower sensitivity of 91.1% compared to 96.2% (p = 0.008) at its optimum cut-off (0.168 IU/mL) with the same specificity. Moreover, IFN-γ values were significantly reduced with age in QFT-GIT (p = 0.035) but not in QFT-Plus. The diagnostic performance of QFT-Plus was as accurate as that of QFT-GIT despite a lack of TB7.7 antigen and despite the decrease in quantitative values. However, the cut-off value for QFT-Plus should be considered independently from that of QFT-GIT to obtain the best sensitivity without compromising specificity.
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http://dx.doi.org/10.1038/srep30617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965764PMC
July 2016
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