Phenotypic and genomic insights into the pathogenicity and antimicrobial resistance of an Enterobacter roggenkampii strain isolated from diseased silver arowana (Osteoglossum bicirrhosum).

Enterobacter roggenkampii is an opportunistic pathogen that causes infections in a wide range of hosts. A bacterial strain named EOBSR_19 was isolated from diseased silver arowana, Osteoglossum bicirrhosum. This bacterium was identified as E. roggenkampii based on the phenotypic characteristics and sequence analysis of the16S rDNA and gyrB genes. Average nucleotide identity and phylogenetic analysis based on the whole genome sequence further confirmed the bacterial taxonomy of EOBSR_19. Artificial experimental infection indicated that EOBSR_19 was pathogenic to fish. Antimicrobial susceptibility test showed it was multi-drug resistant. The EOBSR_19 was found to be resistant to 18 antibiotics belonging to quinolones, macrolides, sulfonamides, aminoglycosides, and ß-lactams classes. The whole genome sequencing analysis showed that EOBSR_19 carried 730 virulence genes that were annotated for different functional modules, such as adhesion and invasion, secretion system, siderophore transport system and bacterial toxin. Among them, the virulence genes related to adhesion and invasion were the most abundant. In addition, drug resistance genes involved in multiple mechanisms of antimicrobial resistance were identified in its genomics, including multidrug resistance efflux pumps, antibiotic inactivating enzymes, and antibiotic binding site mutations. Its genomic analysis via whole-genome sequencing provided insights into the pathogenicity and antimicrobial resistance.

Prognosis-Related Nutritional Score for Cancer Patients (PRNS): a clinical nutritional score derived from a retrospective cohort study.

BACKGROUND: Nutritional assessment and quality of life (QOL) have become important indices for therapeutic efficacy in patients with malignancies. We aim to develop and validate an easy-to-use questionnaire with prognostic value to assess nutritional status in hospitalized cancer patients. METHODS: A comprehensive survey focused on patient-generated subjective global assessment (PG-SGA) and 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30 Chinese version) was performed in a cohort of 22,776 patients derived from the INSCOC study. Among them, 1948 patients were followed for 3 years after admission. An observational, retrospective, cross-sectional cohort study was conducted in accordance with TRIPOD statement. Breiman's random forest model was applied to calculate variable importance (VIMP) for items in PG-SGA and EORTC QLQ-C30 (Chinese version) for nutritional recommendation. Cox regression model was employed to construct Prognosis-Related Nutritional Score for Cancer Patients (PRNS). Kaplan-Meier Survival curve, ROC and DCA were calculated to evaluate prognostic value of nutritional status categorized by PRNS, and compared with PG-SGA. RESULTS: Nutritional status was classified into 4 levels by PRNS scores: well nourished (≤ 4.5 points), mild malnourished (5-7.5 points), moderate malnourished (8-14.5 points), and severe malnourished (≥ 15 points). Significant median overall survival differences were found among nutritional status groups stratified by the PRNS (all Ps < 0.05). Compared with PG-SGA, PRNS had better prognostic value for survival stratified by nutritional status. The external, internal validity, test-retest reliability and rater reliability were satisfactory. CONCLUSIONS: We systematically developed and validated PRNS as a nutrition screening tool for cancer patients. Compared with PG-SGA, PRNS has better prognostic value and simpler operation. TRIAL REGISTRATION: Investigation on Nutrition Status and its Clinical Outcome of Common Cancers, ChiCTR1800020329. Registered 24 December 2018-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=31813.

Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome.

Background: Chronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification. Methods: Data-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay in an independent prospective cohort. Results: Fifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone. Conclusion: Plasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS.

A Four-Gene-Based Risk Score With High Prognostic Value in Gastric Cancer.

BACKGROUND: Gastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma. MATERIALS AND METHODS: We extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan-Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature. RESULTS: Forty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33-2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort. CONCLUSION: A four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.

Increased Risk of Clopidogrel-Induced Gastric Mucosal Erosion in Elderly Chinese Men Harboring the ABCB1 3435T Allele.

BACKGROUND: It is uncertain whether long-term use of clopidogrel alone can cause gastric mucosal injury. This study aimed to evaluate the relationship between ABCB1 C3435T polymorphisms, which could affect the intestinal absorption of clopidogrel, and gastric mucosal erosion in elderly Chinese men who used clopidogrel alone. METHODS: We selected 298 male patients (aged between 68.2 and 89.5 years, average age 78); 201 of them constituted the control group, and 97 constituted the case group. Patients taking clopidogrel alone who had undergone endoscopic screening for gastric erosion were analyzed for ABCB1 C3435T polymorphisms by a TaqMan assay. RESULTS: The proportion of people carrying the ABCB1 3435T allele (n = 63, 64.9% vs n = 97, 48.3%, p = 0.007) was significantly higher in the case group than in the control group. After adjustments for significant factors were made, ABCB1 3435T allele carrier (OR 2.14, 95% CI 1.43-3.84, p <0.01) was found to be associated with gastric mucosal erosion in people who used clopidogrel alone. CONCLUSION: Carrying the ABCB1 3435T allele may be a useful genetic predictor for clopidogrel-induced gastric mucosal erosion in elderly Chinese men.

Effects of cigarette smoking on older chinese men treated with clopidogrel monotherapy or aspirin monotherapy: a prospective study.

We investigated the comparative effects of smoking status on outcomes in older Chinese men receiving aspirin or clopidogrel monotherapy. This was a prospective observational study of outcomes in 668 men aged ≥ 60 years undergoing annual health examination in the Chinese People's Liberation Army General Hospital from March-April 2017. All patients received regular treatment with aspirin or clopidogrel. Platelet aggregation and phenotyping for rs762551 were measured in all patients. We recorded all major adverse cardiovascular and cerebrovascular events; namely, all-cause death, myocardial infarction, stroke, transient ischemic attack, and unstable angina. In the clopidogrel subgroup, homozygous carriers (AA) of the CYP1A2*1F gene (rs762551, 163C>A) appeared more frequently in smokers than in nonsmokers (45.6% vs 32.7%, p = .035). Adenosine diphosphate-induced platelet aggregation using light transmittance aggregometry was lower in smokers compared with nonsmokers (44.97 ± 20.05% vs 51.98 ± 19.38%, respectively; p = .0018). Smokers (n = 103) had a decreased risk of major adverse cardiovascular and cerebrovascular events, compared with nonsmokers [n = 159; hazard ratio, 0.466; 95% confidence interval: 0.262-0.829, p = .008]. In the aspirin subgroup, AA-induced platelet aggregation showed no significant difference regarding smoking vs nonsmoking status (30.90 ± 32.21 vs 29.78 ± 31.47, respectively; p = .771). However, we saw a significant increase in adverse clinical events in the smoking group (n = 148) compared with the nonsmoking group (n = 258; hazard ratio = 1.907, 95% confidence interval: 1.128-3.225; p = .016). In older Chinese men, active smokers benefitted from clopidogrel therapy compared with aspirin. Long-term cigarette smoking may contribute to increased variations in CYP1A2*1F, but the variations do not fully explain the smoking paradox.

Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer.

Colorectal cancer (CRC) is one of the most common types of malignant tumor. Many genetic factors have been proved to show high association with the occurrence and development of CRC and many mutations are detected in CRC. PTPN4/PTP-MEG1 is a widely expressed non-receptor protein tyrosine phosphatase. Over the past three decades, PTPN4 has been demonstrated in the literature to participate in many biological processes. In this study, we identified a nonsense mutation of PTPN4 with a mutation ratio of 90.90% from 1 case of rectal cancer, leading to loss of function in PTPN4 gene. Several somatic mutations occurred in 5/137 rectal cancer samples from The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA READ) database. Interestingly, we found that PTPN4 negative cytoplasm staining was more prone to lymphatic metastasis (N = 50, P = 0.0153) and low expression of PTPN4 in rectal cancer was highly associated with poor prognosis. Overexpression of PTPN4 suppressed the cell growth, and moreover, the loss of PTPN4 accelerated cell growth and boosted clonogenicity of CRC cells. Furthermore, we revealed that the deletion of PTPN4 promoted the tumor formation of NCM460 cells in vivo. In terms of the molecular mechanism, we demonstrated that PTPN4 dephosphorylates pSTAT3 at the Tyr705 residue with a direct interaction and suppresses the transcriptional activity of STAT3. In summary, our study revealed a novel mechanism that the tumorigenesis of colorectal cancer might be caused by the loss of PTPN4 through activating STAT3, which will broaden the therapy strategy for anti-rectal cancer in the future.

Usefulness of the CHADS2 and R2CHADS2 scores for prognostic stratification in patients with coronary artery disease.

OBJECTIVE: The current risk model for long-term prediction in coronary artery disease (CAD) is complicated, while a simple useful model is still lacking. We aim to investigate if CHADS2 and R2CHADS2 scores could predict long-term outcome for patients with CAD. PATIENTS AND METHODS: We enrolled 3,700 patients with CAD between November 2010 and September 2014 at the Department of Cardiology from Chinese PLA General Hospital. The CHADS2 and R2CHADS2 scores were calculated. All cases were followed to track the incidence of composite end point consisting of cardiovascular (CV) death, myocardial infarction (MI), stroke, heart failure, and all-cause death. RESULTS: During a median 2.9-year follow-up, 443 patients experienced at least one element of the composite end point of CV death (n=168 [4.6%]), MI (n=59 [1.6%]), stroke (n=96 [2.6%]), heart failure (n=101 [2.8%]), and all-cause death (n=240 [6.6%]). Multivariate Cox regression analyses showed that the CHADS2 score (hazard ratio [HR]: 2.18, 95% CI: 2.00-2.38, p<0.0001) and the R2CHADS2 score (HR: 1.93, 95% CI: 1.83-2.04, p<0.0001) were independently associated with composite outcome. Receiver-operating characteristic analysis showed that compared with the CHADS2 score, the R2CHADS2 score had better discrimination for the prediction of long-term combined outcome (0.772 vs 0.791, p=0.0013). CONCLUSION: CHADS2 and R2CHADS2 scores provide a quick and useful tool in predicting long-term outcome for patients with CAD.