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Background: Solithromycin, the fourth generation of ketolides, has been demonstrated potent antibacterial effect against commonly-isolated gram-positive strains. However, Staphylococcus aureus (S. aureus) strains with a higher solithromycin MIC have already been emerged, the mechanism of which is unknown., Methods: Antimicrobial susceptibility test was performed on 266 strains of S. aureus. The antibiotic resistance phenotype of erm-positive strain was determined by D-zone test. Spontaneous mutation frequency analysis was performed to compare the risk levels for solithromycin resistance among different strains. Efflux pumps and mutational analysis of ribosomal fragments as well as erm(B) gene domains were detected. Quantitative reverse transcription polymerase chain reaction was conducted to compare the transcriptional expression of the erm gene between the constitutive macrolide-lincosamide-streptogramin B (cMLSB)- and inducible MLSB (iMLSB)-phenotypes., Results: In the erm-positive S. aureus strains, the minimum inhibitory concentration (MIC) 50/90 of solithromycin (2/> 16 mg/L) was significantly higher than that in the erm-negative strains (0.125/0.25 mg/L). Of note, the MIC 50 value of the strains with iMLSB (0.25 mg/L) was significantly lower than that of the strains with cMLSB (4 mg/L). A comparison among strains demonstrated that the median mutational frequency in isolates with cMLSB (> 1.2 × 10 - 4 ) was approximately > 57-fold and > 3333-fold higher than that in iMLSB strains (2.1 × 10 - 6 ) and in erythromycin-sensitive strains (3.6 × 10 - 8 ), respectively. The differential antibiotic in vitro activity against strains between cMLSB and iMLSB could not be explained by efflux pump carriers or genetic mutations in the test genes. The expression of the erm genes in strains with cMLSB did not differ from that in strains with iMLSB., Conclusions: The reduced susceptibility to solithromycin by S. aureus was associated with the cMLSB resistance phenotype mediated by erm.

Serum lipid levels have been investigated as prognostic markers in patients with acute ischaemic stroke. However, these results remain inconsistent. This study aimed at assessing the association between serum lipid and clinical outcomes in acute ischaemic stroke. Relevant data were obtained from Cochrane Library, PubMed and Web of Science databases. The heterogeneity of pooled results was determined by the Cochran's Q test and Higgins I-squared statistic. The random-effect model was performed to calculate the pooled results if P H  < 0.05 for Q-test, otherwise the fixed-effect model was applied. The primary results were death, and the secondary were recurrence, dependency, mRS score ≥3, and early neurological deterioration. A total of 21 full-text studies was included in the present study. For primary results, the pooled results from 5 studies with 4119 patients showed that triglyceride (TG) was a significant predictor for death (OR = 0.65, 95%CI = 0.43-0.98, P H  = 0.028). The pooled data from 11 studies with 12,486 patients for total cholesterol (TC), 4 studies with 7593 patients for low-density lipoprotein cholesterol (LDL-C), and 5 studies with 6933 patients for high-density lipoprotein cholesterol (HDL-C) suggested that TC (OR = 0.79, 95%CI = 0.56-1.13, P H  < 0.001), LDL-C (OR = 1.02, 95%CI = 0.66-1.57, P H  = 0.042), and HDL-C (OR = 1.18, 95%CI = 0.75-1.86, P H  = 0.003) were not associated with death in acute ischaemic stroke. For secondary results, the pooled results of 2 studies with 867 patients indicated that TG was positively associated with early neurological deterioration. This study suggested that serum TG was associated with death and early neurological deterioration in acute ischaemic stroke., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Although combination antiretroviral therapy (cART) is highly effective in suppressing human immunodeficiency virus type 1 (HIV-1) replication, it fails to eradicate the virus from HIV-1-infected individuals because HIV-1 integrates into the resting CD4 + T cells, establishing latently infected reservoirs. Histone deacetylation is a key element in regulating HIV-1 latent infection. Chidamide, a new anticancer drug, is a novel type of selective histone deacetylase inhibitor. Here we showed that chidamide effectively reactivated HIV-1 latent provirus in different latently infected cell lines in a dose- and time-dependent manner. Chidamide had relatively low cytotoxicity to peripheral blood mononuclear cells (PBMCs) and other latent cell lines. We have demonstrated that chidamide reactivated HIV-1 latent provirus through the NF-κB signaling pathway. The replication of the newly reactivated HIV-1 could then be effectively inhibited by the anti-HIV-1 drugs Zidovudine, Nevirapine, and Indinavir. Therefore, chidamide might be used in combination with cART for functional HIV-1 cure., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Enterococcal infections have become one of the most challenging nosocomial problems. Tedizolid, the second oxazolidinone, is 4-fold to 8-fold more potent in vivo and in vitro than linezolid against enterococci. However, the characteristics of tedizolid related to enterococci isolates in China remain elusive. The aim of this study was to evaluate in vitro activity of tedizolid against enterococcal isolates from patients with infections at a teaching hospital in China and to investigate the correlations between in vitro tedizolid activity against enterococci and the distribution of multilocus sequence types (MLST), resistance genes and virulence factors. A total of 289 non-duplicate Enterococcus faecalis strains and 68 E. faecium strains were isolated. Tedizolid inhibited 95.24% of all enterococcal isolates with an MIC ≤ 0.5μg/ml. Seventeen E. faecalis strains had an MIC > 0.5 μg/ml, and all E. faecium were inhibited at MIC ≤ 0.5 μg/ml. The proportion of tedizolid non-susceptible E. faecalis strains with optrA genes was higher than that among tedizolid-susceptible strains. Tedizolid exhibited good in vitro activity against all E. faecium strains, including multidrug-resistant E. faecium carrying tet(M), tet(L), tet(U),erm(A), erm(B) and erm(C) genes. In summary, tedizolid has an advantage (higher sensitivity rate) compared to linezolid among enterococci, except for isolates expressing the plasmid-encoded optrA gene., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In early 2014, a novel subclade (2.3.4.4) of the highly pathogenic avian influenza (HPAI) A(H5N8) virus caused the first outbreak in domestic ducks and migratory birds in South Korea. Since then, it has spread to 44 countries and regions. To date, no human infections with A(H5N8) virus have been reported, but the possibility cannot be excluded. By analyzing the genomic signatures of A(H5N8) strains, we found that among the 47 species-associated signature positions, three positions exhibited human-like signatures (HLS), including PA-404S, PB2-613I and PB2-702R and that mutation trend of host signatures of avian A(H5N8) is different before and after 2014. About 82% of A(H5N8) isolates collected after January of 2014 carried the 3 HLS (PA-404S/PB2-613I/PB2-702R) in combination, while none of isolates collected before 2014 had this combination. Furthermore, the HA protein had S137A and S227R substitutions in the receptor-binding site and A160T in the glycosylation site, potentially increasing viral ability to bind human-type receptors. Based on these findings, the newly emerged HPAI A(H5N8) isolates show an evolutionary trend toward gaining more HLS and, along with it, the potential for bird-to-human transmissibility. Therefore, more extensive surveillance of this rapidly spreading HPAI A(H5N8) and preparedness against its potential pandemic are urgently needed., (Copyright © 2017. Published by Elsevier Masson SAS.)

Time is an important aspect of information and is very useful for information utilization. The goal of this study was to analyze the challenges of temporal expression (TE) extraction and normalization in Chinese clinical notes by assessing the performance of a rule-based system developed by us on a manually annotated corpus (including 1,778 clinical notes of 281 hospitalized patients). In order to develop system conveniently, we divided TEs into three categories: direct, indirect and uncertain TEs, and designed different rules for each category of them. Evaluation on the independent test set shows that our system achieves an F-score of93.40% on TE extraction, and an accuracy of 92.58% on TE normalization under "exact-match" criterion. Compared with HeidelTime for Chinese newswire text, our system is much better, indicating that it is necessary to develop a specific TE extraction and normalization system for Chinese clinical notes because of domain difference.

Despite recent progress in prediction and prevention, heart disease remains a leading cause of death. One preliminary step in heart disease prediction and prevention is risk factor identification. Many studies have been proposed to identify risk factors associated with heart disease; however, none have attempted to identify all risk factors. In 2014, the National Center of Informatics for Integrating Biology and Beside (i2b2) issued a clinical natural language processing (NLP) challenge that involved a track (track 2) for identifying heart disease risk factors in clinical texts over time. This track aimed to identify medically relevant information related to heart disease risk and track the progression over sets of longitudinal patient medical records. Identification of tags and attributes associated with disease presence and progression, risk factors, and medications in patient medical history were required. Our participation led to development of a hybrid pipeline system based on both machine learning-based and rule-based approaches. Evaluation using the challenge corpus revealed that our system achieved an F1-score of 92.68%, making it the top-ranked system (without additional annotations) of the 2014 i2b2 clinical NLP challenge., (Copyright © 2015 Elsevier Inc. All rights reserved.)

De-identification, identifying and removing all protected health information (PHI) present in clinical data including electronic medical records (EMRs), is a critical step in making clinical data publicly available. The 2014 i2b2 (Center of Informatics for Integrating Biology and Bedside) clinical natural language processing (NLP) challenge sets up a track for de-identification (track 1). In this study, we propose a hybrid system based on both machine learning and rule approaches for the de-identification track. In our system, PHI instances are first identified by two (token-level and character-level) conditional random fields (CRFs) and a rule-based classifier, and then are merged by some rules. Experiments conducted on the i2b2 corpus show that our system submitted for the challenge achieves the highest micro F-scores of 94.64%, 91.24% and 91.63% under the "token", "strict" and "relaxed" criteria respectively, which is among top-ranked systems of the 2014 i2b2 challenge. After integrating some refined localization dictionaries, our system is further improved with F-scores of 94.83%, 91.57% and 91.95% under the "token", "strict" and "relaxed" criteria respectively., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate whether Clostridium difficile infection (CDI) contributed to hospital mortality and whether the correlation between intensive care units (ICUs) and surgical wards in hospital CDI risk still remain controversial., Methods: By meta-analysis, 12 eligible studies involving 8,509 cases and 247,285 controls were identified via PubMed and Embase., Results: CDI patients had a higher risk of hospital mortality than non-CDI patients (odds ratio [OR], 1.899; 95% confidence interval [CI], 1.269-2.840), especially in 30-day mortality (OR, 2.521; 95% CI, 1.800-3.531). No correlation was found between hospital CDI and Charlson comorbidity index (OR, 0.830; 95% CI, 0.559-1.231). Patients treated in the ICU have an increased risk of hospital CDI (OR, 1.820; 95% CI, 1.161-2.851). However, the risk of CDI in patients who used to have surgery in surgical wards was not different to patients in the other departments (OR, 1.054; 95% CI, 0.838-1.325). Moreover, CDI patients in studies from the most recent 5 years have a higher risk of hospital mortality (OR, 2.171; 95% CI, 1.426-3.304)., Conclusion: Hospital CDI was associated with an increased risk of hospital mortality, especially in 30-day mortality. In addition, when compared with past years, CDI patients have a higher risk of hospital mortality in the most recent 5 years. Given the rapid dissemination of this organism worldwide, there is a need to aggressively develop and evaluate primary preventive strategies targeting CDI among hospitalized patients, especially in ICUs., (Copyright © 2015. Published by Elsevier Inc.)

Polymorphisms in microRNA (miRNA) have been discussed to be associated with breast cancer risk; however, the conclusions were always inconsistent in different ethnicities. This case-control study enrolled 450 breast cancer cases, and 450 health controls was carried out to investigate the association between six polymorphisms in miRNAs and breast cancer risk. Sequenom MassARRAY was used to detect the polymorphisms in miRNAs, and the immunohistochemistry assay was applied to detect the expression of estrogen receptor (ER) and progesterone receptor (PR) in cancer tissue. The data showed that the 3746444 GG was associated with increased breast cancer risk (adjusted odds ratio (OR) = 1.71, 95 % confidence interval (CI) = 1.16-2.52) and that rs2292832 CC (adjusted OR = 0.54, 95 % CI = 0.34-0.85) was associated with decreased breast cancer risk. In addition, menopausal status subgroup analysis revealed that rs3746444 GG (adjusted OR = 2.34, 95 % CI = 1.31-4.15) and GA/GG (adjusted OR = 1.60, 95 % CI = 1.08-2.37) genotypes were associated with increased breast cancer risk for the subgroup of women with premenopausal status, respectively. Moreover, rs2910164 GG (adjusted OR = 1.84, 95 % CI = 1.07-3.15) and CG/GG (adjusted OR = 1.47, 95 % CI = 1.01-2.15) genotypes were associated with increased breast cancer risk in the postmenopausal status subcohort, respectively. Furthermore, rs3746444 AG (adjusted OR = 1.61, 95 % CI = 1.06-2.45) and AG/GG (adjusted OR = 1.49, 95 % CI = 1.02-2.18) genotypes were observed to be associated with increased risk of lymph node involvement and breast cancer with negative PR expression, separately. In short, rs3746444 was associated with breast cancer risk, especially for women with premenopausal status, and rs2910164 CG and CG/GG genotypes were associated with breast cancer risk for the women with premenopausal status.

Inflammation is an essential component of pathogenesis and progression of cancer. A high neutrophil-to-lymphocyte ratio (NLR) is considered as a prognostic indicator for breast cancer. This meta-analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted by using PubMed, Web of Science and China National Knowledge Infrastructure (CNKI). Published studies dating up to July 2014 and 4,293 patients were enrolled in the present study. In order to evaluate the association between NLR and overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) or cancer specific survival (CSS), the hazard ratios (HRs) and their 95% confidence intervals (CIs) were extracted. OS was the primary outcome. The results suggested that increased NLR was a strong predictor for OS with HR of 2.28 (95% CI = 1.08-4.80, Pheterogeneity < 0.001). Stratified analyses indicated that a high NLR appeared to be a negative prognostic marker in Caucasian populations (HR = 4.53, 95% CI = 3.11-6.60, Pheterogeneity  = 0.096), multivariate analysis method (HR = 2.10, 95% CI = 1.52-2.89, Pheterogeneity = 0.591), and mixed metastasis (HR = 4.53, 95% CI = 3.11-6.60, Pheterogeneity = 0.096). Elevated NLR was associated with a high risk for DFS (HR = 1.38, 95% CI = 1.09-1.74, Pheterogeneity = 0.050) and in subgroups of multivariate analysis (HR = 1.64, 95% CI = 1.25-2.14, Pheterogeneity = 0.545) and mixed metastasis (HR = 1.99, 95% CI = 1.28-3.09, Pheterogeneity = 0.992). In summary, NLR could be considered as a predictive factor for patients with breast cancer.

Purpose: Glutathione S-transferases (GSTs) are involved in the detoxification of carcinogens, and may be linked to carcinogenesis. As a vital component of GSTs, GSTA1 plays an important role in carcinogenesis. However, the studies about the effect of GSTA1 polymorphisms on cancer risk are limited and the conclusions are contradictory. This meta-analysis aimed to evaluate the association between GSTA1 polymorphisms (-567T>G, (69C>T and -52G>A) and cancer risk., Methods: A literature search of PubMed and Web of Science databases was conducted from their inception through December 2013. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of GSTA1 polymorphisms and cancer risk., Results: A total of 15 studies were enrolled, and the results indicated that GSTA1 BB genotype was associated with elevated cancer risk, especially in colorectal cancer. Further stratifications showed that GSTA1 BB genotype was associated with increased cancer risk in Caucasian populations and in the study with population-based controls., Conclusions: This meta-analysis suggested that GSTA1 BB genotype was a risk factor for colorectal cancer, especially in Caucasian populations.

Purpose: Emerging published reports on the association between estrogen receptor 1 (ESR1) genetic variation and cancer susceptibility are inconsistent. This review and meta- analysis was performed to achieve a more precise evaluation of this relationship., Methods: A literature search of PubMed database was conducted from the inception of this study through April 1st 2014. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the association., Results: 87 studies were enrolled in this meta-analysis. The results indicated that PvuII (T>C) polymorphism was associated with an increased risk of hepatocellular carcinoma (HCC) and prostate cancer, in contrast with the decreased risk of gallbladder cancer. No significant association was found in Asian and Caucasian populations. Furthermore, XbaI (A>G) genetic variation was only associated with an increased risk of prostate cancer, but was not related with race. In addition, T594T (G>A) polymorphisms were significantly associated with an increased risk of cancer, especially in Asian populations., Conclusions: This meta-analysis indicated that PvuII (T>C) genetic variation may be risk factor for HCC, prostate cancer and gallbladder cancer. Meanwhile, XbaI (A>G) polymorphism may be potential prognostic factor for prostate cancer. Furthermore, T594T (G>A) was closely related with cancer susceptibility, especially in Asian populations.

IL-12 plays an important role in the treatment of many infectious diseases by being administered intravenously or intramuscularly. However, intravenous or intramuscular administration is difficult and inconvenient and may cause side effects. The aim of this study is to develop a novel oral delivery system for IL-12 using genetically engineered Bifidobacterium longum as the carrier and further investigate the efficacy of IL-12-expressed B. longum on the coxsackie virus B3 (CVB3)-induced myocarditis in mice. A mIL-12 gene expression vector pBBADs-IL-12 for B. longum was constructed and transformed into Bifidobacterium. Subsequently, the expression of mIL-12 in the engineered B. longum was identified in vitro by western blot and enzyme-linked immunosorbent assay (ELISA) after l-arabinose induction. Moreover, our data indicated that oral administration of IL-12-expressed B. longum for two weeks after CVB3 infection in the Balb/c mice could downregulate the severity of virus-induced myocarditis, markedly reduce the virus titers in the heart and induce a Th1 pattern in the spleen and heart compared with the controls. In conclusion, a novel oral delivery system of Bifidobacterium for murine IL-12 has been successfully established. Oral administration of mIL-12-transformed B. longum may play a therapeutic role in the treatment of CVB3-induced myocarditis in the mice., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Multiple reports have claimed that low-dose orally administered interferon (IFN)-α is beneficial in the treatment of many infectious diseases and provides a viable alternative to high-dose intramuscular treatment. However, research is needed on how to express IFN stably in the gut. Bifidobacterium may be a suitable carrier for human gene expression and secretion in the intestinal tract for the treatment of gastrointestinal diseases. We reported previously that Bifidobacterium longum can be used as a novel oral delivery of IFN-α. IFN-transformed B. longum can exert an immunostimulatory role in mice; however the answer to whether this recombinant B. longum can be used to treat virus infection still remains elusive. Here, we investigated the efficacy of IFN-transformed B. longum administered orally on coxsackie virus B3 (CVB3)-induced myocarditis in BALB/c mice. Our data indicated that oral administration of IFN-transformed B. longum for 2 weeks after virus infection reduced significantly the severity of virus-induced myocarditis, markedly down regulated virus titers in the heart, and induced a T helper 1 cell pattern in the spleen and heart compared with controls. Oral administration of the IFN-transformed B. longum, therefore, may play a potential role in the treatment of CVB3-induced myocarditis.