CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

Active Stat3 and Her-2 as combined survival predictors show superiority to TNM staging system for postoperative patients with gastric cancer.

OBJECTIVES: TNM staging of gastric cancer (GC) is useful in predicting prognosis, but its definition is only possible after surgery. It is therefore desirable to develop a method that can predict prognosis and assist management options before surgery. METHODS: This study investigated 110 GC patients after radical gastrectomy and followed-up for 136 months. Patients' complete clinicopathological data were collected and gastroscopically biopsied or surgically resected tissues were examined for the expression of Her-2, nm-23, CEA and phosphorylated Stat3 (p-Stat3) using immunohistochemistry (IHC). Univariate and multivariate ROC curves, Kaplan-Meier survival curves, and SPSS Version 22.0 and R (version 3.6.1) statistical software were used to analyze the data. RESULTS: Three major findings were observed: (1) Tissue levels of p-Stat3, Her-2, CEA and nm-23 were correlated with GC patients' survival probability termed as survival prediction power (SPP). (2) Using 5-year survival as an end-point, the SPP of the p-Stat3+Her-2 combination was stronger (AUC=0.867) than that of TNM staging (AUC=0.755). (3) Using cut-off values derived from ROC curves, Kaplan-Meier analyses showed that the p-Stat3+Her-2 molecular combination could clearly predict overall survival rates between the predictive low-risk patients (69.2%) and the predictive high-risk patients (13.2%) with a discriminative difference as high as 56.0%. CONCLUSIONS: We conclude that area under the ROC curve (AUC) can be used to quantify SPP powers for biomarkers, making cross-comparisons possible among different survival predictors. This study has first established a multi-factor survival prediction model by which the p-Stat3+Her-2 combination has the best discriminative capability to differentiate low-risk patients from high-risk patients in terms of survival prognosis.

[Temporal-spatial and non-stationarity characteristics of extreme precipitation in the Poyang Lake Basin, China]. / 鄱阳湖流域极端降水时空分布和非平稳性特征.

Extreme weather/climate events increased significantly because of global warming. Based on daily records from 16 meteorological stations in the Poyang Lake Basin (PLB) from 1959 to 2019, we comprehensively investigated the temporal-spatial and non-stationarity characteristics of extreme precipitation from three dimensions (intensity, frequency and duration) using PreWhite-ning Mann-Kendall (PWMK), extreme-point symmetric mode decomposition method (ESMD) and the generalized additive models for location, scale and shape (GAMLSS). The results showed that the intensity and frequency of extreme precipitation increased significantly in the PLB, while the duration of extreme precipitation decreased from 1959 to 2019. The extreme precipitation had features of high intensity, high frequency, and short duration in the PLB. There was a clear distinction between flood season and non-flood season for extreme precipitation. Extreme precipitation was concentrated in the northern and central PLB during the flood season and in the central PLB during the non-flood season. The increasing trend of extreme precipitation amount was 2.10 mm·a-1 in the Xinjiang basin, which had the largest increment over the PLB. In the flood season, the extreme precipitation had longer duration but weaker intensity and smaller range, contrasting with the status during the non-flood season. The intensity and frequency of extreme precipitation showed stationarity characteristics in the PLB. However, the duration of extreme precipitation showed non-stationarity characteristics. With the continuous increase of extreme precipitation amount, the risk of related disasters would increase.

ß3-adrenoceptor impacts apoptosis in cultured cardiomyocytes via activation of PI3K/Akt and p38MAPK.

ß3-adrenoceptor (ß3-AR) has been shown to promote myocardial apoptosis. However, the exact physiological role and importance of this receptor in the human myocardium, and its underlying mode of action, have not been fully elucidated. The present study aimed to determine the effects of ß3-AR on the promotion of myocardial apoptosis and on norepinephrine (NE) injury. We analyzed NE-induced cardiomyocyte (CM) apoptosis by using a TUNEL and an annexin V/propidium iodide apoptosis assay. Furthermore, we investigated the NE-induced expression of the apoptosis marker genes Akt and p38MAPK, their phosphorylated counterparts p-Akt and p-p38MAPK, caspase-3, Bcl-2, and Bax. In addition, we determined the effect of a 48-h treatment with a ß3-AR agonist and antagonist on expression of these marker genes. ß3-AR overexpression was found to increase CM apoptosis, accompanied by an increased expression of caspase-3, bax/bcl-2, and p-p38MAPK. In contrast, the ß3-blocker reduced apoptosis of CMs and the associated elevated Akt expression. We identified a novel and potent anti-apoptosis mechanism via the PI3K/Akt pathway and a pro-apoptosis pathway mediated by p38MAPK.