ObjectiveThe 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 methodsWe 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.ResultsDuring 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).ConclusionCHADS2 and R2CHADS2 scores provide a quick and useful tool in predicting long-term outcome for patients with CAD.

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.

BackgroundGastric 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 MethodsWe 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.ResultsForty-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 &lt; 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA 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.

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To investigate the effects of different types of lactic acid bacteria (LAB) on aerobic stability, microbial community and metabolites of whole crop corn silage ensiled with Lentilactobacillus plantarum (LP) and Lentilactobacillus buchneri (LB) or not (CK), the fermentation parameters, aerobic stability, microbial community and metabolite differential components of whole crop corn silage were analyzed after ensiling for 8 months. The results showed that the pH of the whole treatment was lower than 4.2, which indicates good fermentation quality. Compared with the LP group, the LB group significantly improved the aerobic stability of whole crop corn silage (p < 0.05). The addition of LB and LP both increased the number of LAB and the relative abundance of Lentilactobacillus. Metabolite analysis results showed that 28 metabolites were significantly different between the LP and CK groups (p < 0.01), 15 metabolites were significantly different between the LB and CK groups (p < 0.01), and 17 metabolites were significantly different between the LP and LB groups (p < 0.01). The antioxidant metabolites 9-oxo-10(E), 12(E)-octadecadienoic acid and 9(Z),11(E),13(E)-octadecatrienoic acid ethyl ester in the LB group were significantly higher than those in the lp group (p < 0.01). Therefore, compared with LP, obligate heterofermentative LB is more beneficial to maintain the stability of whole crop corn silage after cellar opening.