CPEB3 suppresses gastric cancer progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies.

Deciphering the crosstalk between RNA-binding proteins and corresponding RNAs will provide a better understanding of gastric cancer (GC) progression. The comprehensive bioinformatics study identified cytoplasmic polyadenylation element-binding protein 3 (CPEB3) might play a vital role in GC progression. Then we found CPEB3 was downregulated in GC and correlated with prognosis. In addition, CPEB3 suppressed GC cell proliferation, invasion and migration in vitro, as well as tumor growth and metastasis in vivo. Mechanistic study demonstrated CPEB3 interacted with 3'-UTR of ADAR1 mRNA through binding to CPEC nucleotide element, and then inhibited its translation by localizing it to processing bodies (P bodies), eventually leading to the suppression of ADAR1-mediated RNA editing. Microscale thermophoresis assay further revealed that the direct interaction between CPEB3 and GW182, the P-body's major component, was through the 440-698AA region of CPEB3 binding to the 403-860AA region of GW182. Finally, AAV9-CPEB3 was developed and administrated in mouse models to assess its potential value in gene therapy. We found AAV9-CPEB3 inhibited GC growth and metastasis. Besides, AAV9-CPEB3 induced hydropic degeneration in mouse liver, but did not cause kidney damage. These findings concluded that CPEB3 suppresses GC progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies.

Development and validation of a survival nomogram for patients with Siewert type II/III adenocarcinoma of the esophagogastric junction based on real-world data.

BACKGROUND: The clinical staging systems for adenocarcinoma of the esophagogastric junction (AEG) are controversial. We aimed to propose a prognostic nomogram based on real-world data for predicting survival of Siewert type II/III AEG patients after surgery. METHODS: A total of 396 patients with Siewert type II/III AEG diagnosed and treated at the Center for Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-sen University, from June 2009 to June 2017 were enrolled. The original data of 29 variables were exported from the electronic medical records system. The nomogram was established based on multivariate Cox regression coefficients, and its performance was measured using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve analysis and calibration curve. RESULTS: A nomogram was constructed based on nine variables. The C-index for overall survival (OS) prediction was 0.76 (95% CI, 0.72 to 0.80) in the training cohort, in the validation-1 cohort was 0.79 (95% CI, 0.72 to 0.86), and 0.73 (95% CI, 0.67 to 0.80) in the validation-2 cohort. Time-dependent ROC curves and calibration curves in all three cohorts showed good prognostic predictive accuracy. We further proved the superiority of the nomogram in predictive accuracy for OS to pathological TNM (pTNM) staging system and other independent prognostic factors. Kaplan-Meier survival curves demonstrated the pTNM stage, grade of differentiation, positive lymph node, log odds of positive lymph node and organ invasion were prognostic factors with good discriminative ability. CONCLUSION: The established nomogram demonstrated a more precise prognostic prediction for patients with Siewert type II/III AEG.

The Association between the Participation of Quality Control Circle and Patient Safety Culture.

Promoting patient safety culture (PSC) is a critical issue for healthcare providers. Quality control circles program (QCCP) can be used as an effective tool to foster long-lasting improvements on the quality of medical institution. The effect of QCCP on PSC is still unknown. This was a retrospective study conducted with matching data. A safety attitudes questionnaire (SAQ) was used for the evaluation of PSC. The association between all scores of six subscales of SAQ and the participation QCCP were analyzed with both the Mann-Whitney and Kruskal-Wallis tests. A total of 2718 valid questionnaires were collected. Most participants of QCCP were females (78.9%), nurses (52.6%), non-supervisors (92.2%), aged <40 years old (64.8%), degree of specialist or university graduates (78%), and with work experience of <10 years (61.6%). Of all participants, the highest scores were in the dimension of safety climate (74.11 ± 17.91) and the lowest scores in the dimension of working conditions (68.90 ± 18.84). The participation of QCCP was associated with higher scores in four dimensions, namely: teamwork climate (p = 0.006), safety climate (p = 0.037), perception of management (p = 0.009), and working conditions (p = 0.015). The participation or not of QCCP had similar results in the dimension of job satisfaction and stress recognition. QCCP was associated with SAQ in subjects with the following characteristics: female, nurse, non-supervisor, aged >50 years old, higher education degrees and with longer working experiences in the hospital. In this first study on the association between each dimension of SAQ and the implementation of QCCP, we found that QCCP interventions were associated with better PSC. QCCP had no benefits in the dimensions of job satisfaction and stress recognition.

BTB domain-containing 7 predicts low recurrence and suppresses tumor progression by deactivating Notch1 signaling in breast cancer.

PURPOSE: BTB domain-containing 7 (BTBD7) has been found to regulate epithelial tissue remodeling and branched organ formation and has been reported to modulate the biological behavior of several cancers. However, its role in breast cancer has not been identified. This study investigated the biological role and prognostic value of BTBD7 in breast cancer. METHODS: We identified the BTBD7 expression pattern using the GENT2 database and assessed its expression in breast cancer tissue and cell lines using quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry. We conducted a clinical relevance and survival analysis on a cohort of 121 breast cancer cases from our follow-up and validated it in a Kaplan-Meier plotter. The gain-loss effect of BTBD7 on cell proliferation, invasion, and migration was detected in vitro. We employed a xenograft mouse metastatic model for in vivo validation and performed a Cignal Finder Cancer 10-Pathway Reporter Array, western blot, immunofluorescence, Cell Counting Kit-8, and transwell invasion/migration assays to analyze the potential mechanism. RESULTS: BTBD7 was downregulated in human breast cancer cell lines and tissues. Decreased BTBD7 expression correlated with a positive lymph node status, lymphovascular invasion, and TNM stage, while high BTBD7 expression correlated with low breast cancer recurrence. BTBD7 suppressed cell proliferation, invasion/migration, and tumor metastasis in breast cancer. The mechanism studied suggested that the inhibitory role of BTBD7 was through the deactivation of Notch1 signaling in breast cancer. CONCLUSION: BTBD7 suppresses tumor progression, and its high expression correlates with low recurrence in breast cancer.

Home-based cardiac rehabilitation improves quality of life, aerobic capacity, and readmission rates in patients with chronic heart failure.

BACKGROUND: Exercise tolerance and cardiac output have a major impact on the quality of life (QOL) of patients experiencing heart failure (HF). Home-based cardiac rehabilitation can significantly improve not only exercise tolerance but also peak oxygen uptake ((Equation is included in full-text article.)peak), and the QOL in patients with HF. The aim of this prospective study was to evaluate the beneficial effects of home-based cardiac rehabilitation on the quality of medical care in patients with chronic HF. METHODS: This study was a randomized prospective trial. HF patients with a left ventricular ejection fraction (LVEF) of less than 50% were included in this study. We randomly assigned patients to the control group (n = 18) and the interventional group (n = 19). Within the interventional group, we arranged individualized rehabilitation programs, including home-based cardiac rehabilitation, diet education, and management of daily activity over a 3-month period. Information such as general data, laboratory data, Cardiopulmonary Exercise Test (CPET) results, Six-minute Walk Test (6MWT) results, and the scores for the Minnesota Living with Heart Failure Questionnaire (MLHFQ) before and after the intervention, was collected from all patients in this study. RESULTS: Patients enrolled in the home-based cardiac rehabilitation programs displayed statistically significant improvement in (Equation is included in full-text article.)peak (18.2 ±â€Š4.1 vs 20.9 ±â€Š6.6 mL/kg/min, P = .02), maximal 6-Minute Walking Distance (6MWD) (421 ±â€Š90 vs 462 ±â€Š74 m, P = .03), anaerobic threshold (12.4 ±â€Š2.5 vs 13.4 ±â€Š2.6 mL/kg/min, P = .005), and QOL. In summary, patients receiving home-based cardiac rehabilitation experienced a 14.2% increase in (Equation is included in full-text article.)peak, a 37% increase in QOL score, and an improvement of 41 m on the 6MWD test. The 90-day readmission rate for patients reduced to 5% from 14% after receiving cardiac rehabilitation. CONCLUSION: Home-based cardiac rehabilitation offered the most improved results in functional capacity, QOL, and a reduced the rate of readmission within 90 days.

Up-regulation of Wnt7b rather than Wnt1, Wnt7a, and Wnt9a indicates poor prognosis in breast cancer.

Aberrant activation of Wnt/ß-catenin signaling is one of the most frequent abnormalities in human cancer, including breast cancer. The prognostic value of Wnt ligands has never been fully characterized. In this study, we focused on four Wnt ligands, namely Wnt1, Wnt7a, Wnt7b and Wnt9a, which were commonly studied and found pivotal in Wnt/ß-catenin signaling, but seldom explored for their prognostic value. We investigated the expression of Wnt1, Wnt7a, Wnt7b and Wnt9a in breast cancer tissues by using real-time PCR and immunohistochemical analysis, and further identified their prognostic significance. Results demonstrated that only Wnt7b expression level in breast cancer was significantly higher than that of benign breast. Spearman rank-correlation analysis revealed the expression level of Wnt1, Wnt7b and Wnt9a, but not Wnt7a, were all significantly associated with positive lymph nodes. The Kaplan-Meier survival curve demonstrated that patients with high Wnt7b expression had a shorter overall survival (OS) and recurrence-free survival (RFS) than those with low Wnt7b expression. Moreover, the univariate and multivariate analysis revealed that Wnt7b expression was an independent prognostic factor for both OS and RFS of breast cancer patients. In addition, the high expression of Wnt7b in breast cancer and its prognostic role were further validated by GENT (Gene Expression database of Normal and Tumor tissues) database and the Kaplan-Meier plotter database. Taken together, we identified that high expression of Wnt7b, rather than Wnt1, Wnt7a and Wnt9a, may serve as a prognostic biomarker for breast cancer.

Collagen triple helix repeat containing-1 negatively regulated by microRNA-30c promotes cell proliferation and metastasis and indicates poor prognosis in breast cancer.

BACKGROUND: Collagen triple helix repeat containing-1 (CTHRC1), which was firstly identified overexpressed in the adventitia and neointima of injured rat arteries, could inhibit collagen expression and increase cell migration. It was then found to be ubiquitously expressed in numerous cell types such as fibroblasts and smooth muscle cells, and aberrantly up-regulated in several malignant tumors. However, the functional role of CTHRC1 and its related mechanism in breast cancer still remains unclear. METHODS: CTHRC1 expressions in breast cancer tissues and cells were assessed by qRT-PCR, western blot and immunohistochemistry. The relative expression level of miR-134, miR-155, miR-30c and miR-630 in breast cancer cells respectively was detected by qRT-PCR. Wild type (Wt) and Mutant type (Mut) CTHRC1 3'UTR sequences were cloned into a psi-CHECK2 reporter vector, and the relative luciferase activity was detected by dual-luciferase reporter assay in indicated cells. The effect of ectopic expression of miR-30c or gain and loss of CTHRC1 on cell viability, cell proliferation, cell cycle progression and apoptosis, cell invasion and migration was respectively detected by CCK-8 assay, colony formation assay, flow cytometry analysis, transwell invasion/migration assay. Protein levels of ß-catenin, active ß-catenin, normal and phosphorylated form of GSK-3ß were detected by western blot in indicated cells. Immunofluorescence staining of ß-catenin was performed to observe nuclear localization. RESULTS: We found CTHRC1 was frequently up-regulated in human breast cancer cells and tissues. Then our cohort study and further meta-analysis validated high expression of CTHRC1 was associated with aggressive clinicopathological features and poor clinical outcome of breast cancer patients. In addition, CTHRC1 promoted cell proliferation, invasion and migration and suppressed cell apoptosis in breast cancer, which might be by activating GSK-3ß/ß-catenin signaling and inhibiting Bax/Caspase-9/Caspase-3 signaling respectively; and these biological functions of CTHRC1 could be directly negatively regulated by miR-30c. CONCLUSION: Taken together, we identified the role of miR-30c/CTHRC1 axis in breast cancer progression and demonstrated CTHRC1 may serve as a prognostic biomarker and therapeutic target for breast cancer.

Up-regulation of the tumor promoter Glyoxalase-1 indicates poor prognosis in breast cancer.

Glyoxalase 1 (Glo1) is an enzyme that plays a role to metabolize and inactivate methylglyoxal. Previous studies also have confirmed that Glo1 is closely related with tumorigenesis, metastasis, and drug-resistant, but its prognostic value in breast cancer has never been explored. In this study, we investigated the expression of Glo1 in breast cancer cell lines and tissues using real-time PCR, western blot and immunohistochemical analysis. We found Glo1 was frequently up-regulated in human breast cancer cells and tissues, and high expression of Glo1 was associated with positive lymph node, lymphovascular invasion, and TNM stage (all P<0.05). The Kaplan-Meier survival curve demonstrated that patients with high Glo1 expression had a shorter overall survival (OS) and recurrence-free survival (RFS) (Both P<0.001) than those with low Glo1 expression. Moreover, the univariate and further multivariate analysis revealed that Glo1 expression was an independent prognostic factor for both OS and RFS of breast cancer patients. Next, with CCK-8 assay, cell apoptosis analysis, colony formation assay, transwell invasion/migration assay, and wound-healing assay, we validated knock-down of Glo1 suppressed invasion and migration and promoted apoptosis of breast cancer cells. Taken together, we demonstrated the tumor-promoter Glo1 may serve as a prognostic biomarker for breast cancer.

Major food safety episodes in Taiwan: implications for the necessity of international collaboration on safety assessment and management.

The major food safety episodes that occurred in Taiwan during the past decade are briefly reviewed in this paper. Among the nine major episodes surveyed, with the exception of a U.S. beef (associated with Creutzfeldt-Jakob disease)-related incident, all the others were associated with chemical toxicants. The general public, which has a layperson attitude of zero tolerance toward food safety, may panic over these food-safety-associated incidents. However, the health effects and impacts of most incidents, with the exception of the melamine incident, were essentially not fully evaluated. The mass media play an important role in determining whether a food safety concern becomes a major incident. A well-coordinated and harmonized system for domestic and international collaboration to set up standards and regulations is critical, as observed in the incidents of pork with ractopamine, Chinese hairy crab with nitrofuran antibiotics, and U.S. wheat with malathion. In the future, it can be anticipated that food safety issues will draw more attention from the general public. For unknown new toxicants or illicit adulteration of food, the establishment of a more proactive safety assessment system to monitor potential threats and provide real-time information exchange is imperative.

[Clinical analysis of medullary carcinoma of the breast].

OBJECTIVE: To assess the clinical manifestation, management and outcome in patients with medullary carcinoma of the breast (MBC). METHODS: Retrospective analysis was carried out on patients with MBC who were admitted from January 1995 to December 1999. RESULTS: A total of 616 female patients treated for breast carcinoma, 26 cases (4.2%) were histopathologically confirmed MBC. The mean age was (45.8 +/- 10.6) years. The tumor size was among 1-5 cm and axillary lymph node involvement was 23.1%; there was no statistically significant correlation between tumor size and metastatic axillary lymph node. Estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu assay were performed immunohistochemically, and the overexpression was 26.3%, 21.1% and 5.3% respectively. All patients underwent operation and polychemotherapy (5-fluorouracil, methotrexate, cyclophosphamide), hormone therapy with Tamoxifen was applied in five patients, and three cases received postoperative irradiation. The follow-up period ranged from 5 to 9 years. Overall five-year survival was 88.4%. CONCLUSIONS: MBC is a favorable histological type of breast carcinoma with good prognosis. Operation and chemotherapy are main procedures for MBC. The significance of molecular biologic parameters in the prognosis of MBC should not be overlooked.