Targeting hTERT Promoter G-Quadruplex DNA Structures with Small-Molecule Ligand to Downregulate hTERT Expression for Triple-Negative Breast Cancer Therapy.

Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand 5 showed high affinity toward hTERT G4 (Kd = 1.1 µM) and potent activity against triple-negative breast cancer cells (MDA-MB-231, IC50 = 1 µM). In cell-based assays, 5 not only exerts markedly inhibitory activity on classical telomere functions including decreased telomerase activity, shortened telomere length, and cellular senescence but also induces DNA damage, acute cellular senescence, and apoptosis. This study reveals that hTERT G4-targeting ligand may cause mitochondrial dysfunction, disrupt iron metabolism and activate ferroptosis in cancer cells. The in vivo antitumor efficacy of 5 was also evaluated in an MDA-MB-231 xenograft mouse model and approximately 78.7% tumor weight reduction was achieved. No observable toxicity against the major organs was observed.

Live Cell Imaging and Real-Time Monitoring of Nucleolus Morphology and Mitophagy with a Red Fluorescent and Photostable rRNA-Specific Probe in Human Cancer Cells.

rRNAs are prevalent in living organisms. They are produced in nucleolus and mitochondria and play essential cellular functions. In addition to the primary biofunction in protein synthesis, rRNAs have been recognized as the emerging signaling molecule and drug target for studies on nucleolus morphology, mitochondrial autophagy, and tumor cell malignancy. Currently, only a few rRNA-selective probes have been developed, and most of them encounter the drawbacks of low water solubility, poor nuclear membrane permeability, short emission wavelength, low stability against photobleaching, and high cytotoxicity. These unfavorable properties of rRNA probes limit their potential applications. In the present study, we reported a new rRNA-selective and near-infrared fluorescent turn-on probe, 4MPS-TO, capable of tracking rRNA in live human cancer cells. The real-time monitoring performance in nucleolus morphology and mitochondrial autophagy is demonstrated in HeLa cells. The probe shows great application potential for being used as a rRNA-selective, sensitive, and photostable imaging tool in chemical biology study and drug screening.

Adrenal limb thickness is associated with metabolism profiles in patients with diabetes: A cross-sectional study.

BACKGROUND: The association between adrenal size and metabolic profiles in patients with diabetes mellitus (DM) is unclear. This study was conducted to determine whether the adrenal thickness measured by computed tomography (CT) is correlated with the metabolic profiles of patients with DM. METHODS: This was a cross-sectional study including 588 Chinese hospitalized patients with DM without comorbidities or medications known to affect adrenal morphology or hormone secretion. Adrenal limb thickness was measured on unenhanced chest CT. Participants were stratified into tertiles according to their total adrenal limb thickness. Linear and logistic regression models were used to estimate the correlations. RESULTS: After adjustment for sex and age, the adrenal thickness was positively associated with body mass index (BMI), waist circumference (WC), urinary albumin/creatinine ratio, and 24-h urinary free cortisol (UFC) and negatively correlated with high-density lipoprotein cholesterol. The sequential equation model (SEM) suggested UFC partially mediated the effect of adrenal limb thickness on WC by 12%. Adrenal thickness, but not UFC, was associated with a higher risk of existing hypertension (odds ratio [OR] = 3.78, 95% confidence interval [CI] 1.58, 9.02) and hyperlipidemia (OR = 2.76, 95% CI 1.03, 7.38), independent of age, gender, BMI, and WC. CONCLUSIONS: The adrenal thickness is independently associated with BMI, WC, cortisol levels, urinary albumin/creatinine ratio, hypertension, and dyslipidemia but not glycemic parameters in patients with diabetes. Our study encourages further studies to investigate the role of adrenal physiology in patients with diabetes.

A Machine Learning-Based Unenhanced Radiomics Approach to Distinguishing Between Benign and Malignant Breast Lesions Using T2-Weighted and Diffusion-Weighted MRI.

BACKGROUND: Breast MRI has been recommended as supplemental screening tool to mammography and breast ultrasound of breast cancer by international guidelines, but its long examination time and use of contrast material remains concerning. PURPOSE: To develop an unenhanced radiomics model with using non-gadolinium based sequences for detecting breast cancer based on T2-weighted (T2W) and diffusion-weighted (DW) MRI. STUDY TYPE: Retrospective analysis followed by retrospective and prospective cohorts study. POPULATION: 1760 patients: Of these, 1293 for model construction (n = 775 for training and 518 for validation). The remaining patients for model testing in internal retrospective (n = 167), internal prospective (n = 188), and external retrospective (n = 112) cohorts. FIELD STRENGTH/SEQUENCE: 3.0T MR scanners from two institution. T2WI, DWI, and first contrast-enhanced T1-weighted sequence. ASSESSMENT: AUCs in distinguishing breast cancer were compared between combined model with gadolinium agent sequence and unenhanced model. Subsequently, the AUCs in testing cohorts of unenhanced model was compared with two radiologists' diagnosis for this research. Finally, patient subgroup analysis in testing cohorts was performed based on clinical subgroups and different types of malignancies. STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis H test, chi-square test, weighted kappa test, and DeLong's test. RESULTS: The unenhanced radiomics model performed best under Gaussian process (GP) classifiers (AUC: training, 0.893; validation, 0.848) compared to support vector machine (SVM) and logistic, showing favorable prediction in testing cohorts (AUCs, 0.818-0.840). The AUCs for the unenhanced radiomics model were not statistically different in five cohorts from those of the combined radiomics model (P, 0.317-0.816), as well as the two radiologists (P, 0.181-0.918). The unenhanced radiomics model was least successful in identifying ductal carcinoma in situ, whereas did not show statistical significance in other subgroups. DATA CONCLUSION: An unenhanced radiomics model based on T2WI and DWI has comparable diagnostic accuracy to the combined model using the gadolinium agent. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Potential-Resolved Electrochemiluminescence Multiplex Immunoassay for Florfenicol and Chloramphenicol in a Single Sample.

The simultaneous detection of multiple antibiotic residues in food is of great significance for food safety. In this work, a novel dual-potential electrochemiluminescence (ECL) immunoassay was designed for the simultaneous detection of chloramphenicol and fluorfenicol residues in food. Ru@MOF was used as an anodic probe, and SnS2 QDs-PEI-Au-MoS2 was used as a cathodic probe. Notably, the coreactant for both luminophores was K2S2O8, avoiding interactions caused by different kinds of coreactants. Au nanoparticles functionalized with a nitrogen- and sulfur-doped graphene oxide-modified glassy carbon electrode to improve the electron transfer efficiency and provide a larger surface area for immobilization of antigen. The linear range for the detection of florfenicol was determined to be 0.1-1000 ng mL-1 with a detection limit of 0.03 ng mL-1, and the linear range for the detection of chloramphenicol was 0.01-1000 ng mL-1 with a detection limit of 3.2 pg mL-1 by recording the ECL responses at two different excitation potentials. The proposed immunoassay achieved a more stable recovery in the detection of actual samples and provided a new analytical method for the simultaneous detection of florfenicol and chloramphenicol residues with high sensitivity and specificity.

Electrochemiluminescence resonance energy transfer immunoassay based on a porphyrin metal-organic framework and AuNPs/NSG for the sensitive detection of zearalenone.

In this study, a novel electrochemiluminescence resonance energy transfer (ECL-RET) immunoassay was developed for the first time for the detection of zearalenone (ZEN). A porphyrin metal-organic framework (PCN-222), an emerging porphyrin-based ECL luminophore, was prepared by a simple hydrothermal method using tetrakis(4-carboxyphenyl) porphyrin, which has excellent ECL emission as well as good ECL efficiency. Because the ECL emission spectrum of PCN-222 is highly matched to the absorption spectrum of gold nanoparticle-modified graphene oxide (AuNPs/NSG) nanocomposites, they were used as donor-acceptor counterparts in this work for the ECL-RET strategy. Under optimal conditions, the ECL immunosensor showed a sensitive response to ZEN in a wide detection range, with a linearity of 0.0005-1000 ng mL-1 and a detection limit of 0.15 pg mL-1. In addition, the sensor showed good potential for application in the detection of wheat and corn samples, providing a new approach for the detection of mycotoxin-like contaminants such as ZEN in food grains.

Multi-center evaluation of machine learning-based radiomic model in predicting disease free survival and adjuvant chemotherapy benefit in stage II colorectal cancer patients.

BACKGROUND: Our study aimed to explore the potential of radiomics features derived from CT images in predicting the prognosis and response to adjuvant chemotherapy (ACT) in patients with Stage II colorectal cancer (CRC). METHODS: A total of 478 patients with confirmed stage II CRC, with 313 from Shanghai (Training set) and 165 from Beijing (Validation set) were enrolled. Optimized features were selected using GridSearchCV and Iterative Feature Elimination (IFE) algorithm. Subsequently, we developed an ensemble random forest classifier to predict the probability of disease relapse.We evaluated the performance of the model using the concordance index (C-index), precision-recall curves, and area under the precision-recall curves (AUCPR). RESULTS: A radiomic model (namely the RF5 model) consisting of four radiomics features and T stage were developed. The RF5 model performed better than simple radiomics features or T stage alone, with higher C-index and AUCPR, as well as better sensitivity and specificity (C-indexRF5: 0.836; AUCPR = 0.711; Sensitivity = 0.610; Specificity = 0.935). We identified an optimal cutoff value of 0.1215 to split patients into high- or low-score subgroups, with those in the low-score group having better disease-free survival (DFS) (Training Set: P = 1.4e-11; Validation Set: P = 0.015). Furthermore, patients in the high-score group who received ACT had better DFS compared to those who did not receive ACT (P = 0.04). However, no statistical difference was found in low-score patients (P = 0.17). CONCLUSION: The radiomic model can serve as a reliable tool for assessing prognosis and identifying the optimal candidates for ACT in Stage II CRC patients. TRIAL REGISTRATION: Retrospectively registered.

Detecting and monitoring tumors in orthotopic colorectal liver metastatic animal models with high-resolution ultrasound.

The ability to noninvasively detect and monitor the growth of orthotopic liver transplantation tumors is critical for replicating advanced colorectal cancer liver metastases (CRLMs) in animal models. We assessed the use of high-resolution ultrasound (HRU) to monitor CRLMs transplanted using various cell concentrations. Sixty BALB/c female mice were randomly divided into 3 groups, and murine colonic CT26 cells were injected into the left liver lobe at concentrations of 1 × 102 (group 1), 1 × 103 (group 2), or 1 × 104 (group 3). Tumor presentation, location, number, size, shape, and echogenicity were assessed daily with 24-MHz center frequency HRU starting 6 days after injection. Animals were sacrificed when the largest tumor was ≥ 1 cm in diameter. Sensitivity, specificity, and area under curve (AUC) of CRLMs diagnosed with HRU were calculated using receiver operating characteristic curve analysis. In group 1, 94% of mice formed < 5 tumors, and 41% formed a single tumor. Tumors were first detected with HRU on day 12 in group 1, day 10 in group 2, and day 7 in group 3; tumor volume doubling times were 14-15 days, 11-12 days, and 7-8 days, respectively. With a long diameter threshold of 2.4 mm, diagnostic sensitivity and specificity of HRU were 94.1% and 88.7%, respectively, and the AUC was 0.962. These findings suggest that HRU can be used to accurately detect and monitor the growth of CRLMs in an orthotopic transplantation mouse model, especially when a lower concentration of cells is used.

Suffering Job Insecurity: Will the Employees Take the Proactive Behavior or Not?

Job insecurity is considered an important antecedent of an employee's creativity. Though, the relationship between job insecurity and proactive behavior has been neglected in previous human resources management studies. The aim of this study is to explore the influence of job insecurity on employees' proactive behavior and its mechanism. Based on the social cognitive theory and cognitive appraisal theory, two types of cognitive appraisal of employee's job insecurity (hindrance vs. challenge) as mediator variables of job insecurity and proactive behavior association. In addition, the moderator roles of self-efficacy are examined. This study is carried out with 257 employees from Chinese firms to examine the hypothesized moderated mediation model by using the hierarchical regression analysis and the bootstrap. The results showed a different effect of job insecurity depending on its conceptualization. The results show that job insecurity has a negative effect on employees' proactive behavior. At the same time, cognitive appraisal of employees' job insecurity mediated the association between job insecurity and employee's proactive behavior. Self-efficacy not only moderates the relationship between job insecurity and cognitive appraisal but also moderate the cognitive appraisal's mediation effect between job insecurity and proactive behavior. The study's theoretical and practical contributions and future research are discussed.

Radiomic signature-based nomogram to predict disease-free survival in stage II and III colon cancer.

PURPOSE: To develop a radiomic nomogram to predict disease-free survival (DFS) in patients with colon cancer. METHODS: We retrospectively identified 302 patients with stage III colon cancer and 269 patients with stage II colon cancer who had undergone multidetector computed tomography (MDCT) and radical resection between January 2009 and December 2015. Patients were divided into a training cohort (n = 322) and an external validation cohort (n = 249). Radiomic features were extracted from MDCT images, and a radiomic signature was built as to predict DFS. A radiomic nomogram integrating the radiomic signature and clinicopathologic characteristics was developed using multivariable logistic regression. The nomogram was evaluated with regard to calibration, discrimination, and clinical utility. RESULTS: The radiomic signature was an independent prognostic factor for DFS in the training cohort (HR = 1.102; 95 % CI: 1.052-1.156; P < 0.001) and the external validation cohort (HR = 1.157; 95 % CI: 1.030-1.301; P = 0.014). The radiomic signature-based nomogram was more effective at predicting DFS than either the TNM staging system or a clinicopathologic nomogram. The C-indices of the radiomic nomogram and TNM staging system were 0.780 (95 % CI: 0.734-0.847) and 0.738 (0.687-0.784) respectively. The radiomic signature-based nomogram demonstrated good fitness (shown by calibration curves) and clinical usefulness (shown by decision curve analysis). CONCLUSION: A radiomic signature derived from MDCT images can effectively predict DFS in patients with stage II and III colon cancer and could be used as a supplement for risk stratification.

A Comparison of Functional Features in Chinese and US Mobile Apps for Diabetes Self-Management: A Systematic Search in App Stores and Content Analysis.

BACKGROUND: Mobile health interventions are widely used for self-management of diabetes, which is one of the most burdensome noncommunicable chronic diseases worldwide. However, little is known about the distribution of characteristics and functions of in-store mobile apps for diabetes. OBJECTIVE: This study aimed to investigate the distribution of characteristics and functions of the in-store mobile apps for self-management of diabetes in the United States and China using a predefined functional taxonomy, which was developed and published in our previous study. METHODS: We identified apps by searching diabetes in English or Chinese in the Apple iTunes Store and Android Markets (both in the United States and China) and included apps for diabetes self-management. We examined the validity and reliability of the predefined functional taxonomy with 3 dimensions: clinical module, functional module, and potential risk. We then classified all functions in the included apps according to the predefined taxonomy and compared the differences in the features of these apps between the United States and China. RESULTS: We included 171 mobile diabetes apps, with 133 from the United States and 38 from China. Apps from both countries faced the challenges of evidence-based information, proper risk assessment, and declaration, especially Chinese apps. More Chinese apps provide app-based communication functions (general communication: Chinese vs US apps, 39%, 15/38 vs 18.0%, 24/133; P=.006 and patient-clinician communication: Chinese vs US apps, 68%, 26/38 vs 6.0%, 8/133; P<.001), whereas more US apps provide the decision-making module (Chinese vs US apps, 0%, 0/38 vs 23.3%, 31/133; P=.001), which is a high-risk module. Both complication prevention (Chinese vs US apps, 8%, 3/38 vs 3.8%, 5/133; P=.50) and psychological care (Chinese vs US apps, 0%, 0/38 vs 0.8%, 1/133; P>.99) are neglected by the 2 countries. CONCLUSIONS: The distribution of characteristics and functions of in-store mobile apps for diabetes self-management in the United States was different from China. The design of in-store diabetes apps needs to be monitored closely.

Effects of Nicorandil on All-Cause Mortality and Cardiac Events in CAD Patients Receiving PCI.

Current studies demonstrating the effects of nicorandil in the prognosis of coronary artery disease (CAD) patients who received percutaneous coronary intervention (PCI) are inconclusive due to the small sample size and small events rate.PubMed, OVID, CBM and CNKI databases were searched using a pre-specified search string to collect randomized controlled trials (RCTs) studying the effects of nicorandil on CAD patients receiving PCI. Data on all-cause mortality and cardiovascular events were collected. RevMan 5.3 software was used for meta-analysis. Subgroup analysis was conducted in patients receiving primary PCI (PPCI) and elective PCI (EPCI).A total of 18 RCTs were included in our final analysis. Nicorandil treatment significantly reduced total mortality in PPCI (Peto OR = 0.44, 95%CI 0.25-0.79, P = 0.006) and EPCI (Peto OR = 0.41, 95%CI 0.25-0.67, P = 0.0004), cardiovascular death in both PPCI (Peto OR = 0.41, 95%CI 0.20-0.84, P = 0.01) and EPCI (Peto OR = 0.40, 95%CI 0.20-0.80, P = 0.009), and heart failure in PPCI (RR = 0.36, 95%CI 0.22-0.59, P < 0.0001). When compared with placebo plus standard treatment or standard treatment alone, nicorandil plus standard treatment was associated with reduced total mortality in both PPCI and EPCI, CV death in EPCI, and heart failure in PPCI. Nicorandil is associated with lower risks of total mortality and CV death in PPCI and EPCI in those who received nicorandil > 28 days.Nicorandil as an adjunct therapy along with PCI is associated with reduced total mortality and cardiovascular death in PPCI and EPCI patients, and reduced heart failure in PPCI patients.

miR-106b targets DAB2 to promote hepatocellular carcinoma cell proliferation and metastasis.

MicroRNAs (miRNAs) have been proven to have important effects on the proliferation and metastasis of multiple cancers, including hepatocellular carcinoma (HCC). In the present study, our aim was to explore the biological function of miR-106b in HCC cell proliferation and metastasis. qPCR analysis showed that miR-106b was expressed at higher levels, while disabled homolog 2 (DAB2) was expressed at lower levels in HCC tissues and cells. Moreover, the aberrant miR-106b expression in HCC affected the cell proliferative and migratory ability by MTT and Transwell assay. DAB2 was identified as a specific target of miR-106b in HCC by luciferase reporter assay and regression analysis showed a negative correlation between DAB2 and miR-106b expression. In addition, DAB2 may attenuate the miR-106b promotion effect on HCC cell proliferation and migration. In short, miR-106b may promote HCC cell proliferation and migration by targeting DAB2.

Low- Versus High-Risk Rectal Cancer Based on MRI Features: Outcomes in Patients Treated Without Neoadjuvant Chemoradiotherapy.

OBJECTIVE: The objective of this study was to compare the prognoses of patients with low- and high-risk rectal cancer detected by MRI who were treated without neoadjuvant chemoradiotherapy (NCRT) and to determine independent risk factors. MATERIALS AND METHODS: This retrospective study included 185 patients with pathologically proven rectal adenocarcinoma who were treated without NCRT. Cancer was defined as high risk if one or more of the following factors were present: extramural depth of tumor invasion greater than 5 mm or stage T4a or T4b for tumor in the mid or high rectum; involvement of intersphincteric space, levators, or adjacent organs for tumor in the low rectum; extramural venous invasion (EMVI); or circumferential resection margin (CRM) involvement. Patients without any of those risk factors were placed in the low-risk group. The Kaplan-Meier method and Cox proportional hazards regression model were used to compare the survival outcomes between the two groups and to investigate the univariate and multivariate influences of the risk factors. RESULTS: Cancer was deemed to be low risk in 65 (35.1%) patients and high risk in 120 (64.9%) patients. The two patient groups had statistically significant differences in 3-year actuarial overall survival (OS; 100% vs 88.3%, p = 0.0044), disease-free survival (DFS; 92.3% vs 60.0%, p < 0.0001), and local recurrence (LR; 1.5% vs 10.0%, p = 0.0297). CRM involvement was identified as an independent risk factor for OS (hazard ratio [HR], 4.78; 95% CI, 1.24-18.45), DFS (HR, 2.44; 95% CI, 1.24-4.81), and LR (HR, 3.92; 95% CI, 1.07-14.41). Moreover, EMVI was identified as an independent risk factor for DFS (HR, 2.46; 95% CI, 1.28-4.74). CONCLUSION: The LR and long-term survival of patients in the low-risk group were more favorable than those of patients in the high-risk group. EMVI and CRM status were independent risk factors.

Electrochemiluminescence based competitive immunoassay for Sudan I by using gold-functionalized graphitic carbon nitride and Au/Cu alloy nanoflowers.

A flower-like Au/Cu alloy nanocomposite (Au/Cu NFs) was synthesized and used in an electrochemiluminescence (ECL) based method for sensitive determination of the dye Sudan I. The Au-g-C3N4 nanosheets as an ECL emitter were prepared by electrostatic adsorption between gold nanoparticles and g-C3N4. They form a film on a glassy carbon electrode (GCE) and then can be connected with Sudan I antigen via gold-nitrogen bond and amidation reactions. The Au/Cu NFs combined with Sudan I antibody also via the Au-N bond and was introduced into the modified GCE by specific recognition between the antibody and the antigen. The overlap between emission spectra of the Au-g-C3N4 nanosheets and absorption spectra of Au/Cu NFs enabled the appearance of ECL resonance energy transfer process. That is, when the Sudan I analyte not present, the ECL was weakened due to absorption by the gray Au/Cu NFs on applying voltages from -1.7 V to 0 V. Conversely, the Au/Cu NFs on the GCE are reduced due to the competition for the antibody between the analyte and the antigen. A strong green ECL emission was obtained. The ECL response is linear in the 0.5 pg mL-1 to 100 ng mL-1 Sudan I concentration range, and the detection limit is 0.17 pg mL-1. Graphical abstract An Au/Cu alloy flower-like nanocomposite (Au/Cu NFs) is firstly synthesized as an acceptor to constitute an electrochemiluminescence-resonance energy transfer (ECL-RET) system for sensitive measurement of Sudan I, while Au nanoparticles (Au NPs) functionalized graphitic carbon nitride (g-C3N4) acted as a donor.

Effect of Cd stress on the bioavailability of Cd and other mineral nutrition elements in broad bean grown in a loess subsoil amended with municipal sludge compost.

Municipal sludge compost (MSC) is commonly used as fertilizer or an amendment in barren soils. However, MSC-borne Cd is of great concern in food safety because of its toxicity. Loess subsoil (LS) is barren and lacks nutrients, but it has a strong ability to absorb and stabilize heavy metals. Hence, LS may be amended with MSC and may reduce the bioavailability of Cd. To simulate the dose effect of the accumulated MSC-borne Cd in amended LS, pot experiments were conducted to study the bioavailability of Cd and other mineral nutrition elements in broad bean (Vicia faba L.) under Cd stress. Plant height and dry biomass remarkably increased as the physicochemical properties of LS were significantly improved; however, they were not significantly influenced by the added Cd. The Cd in the plants grown in MSC amended-LS (P2) mainly accumulated in roots (32.12 mg kg-1) and then in stems and leaves (6.00 mg kg-1). Less Cd (0.74 mg kg-1) accumulated in the edible parts, where the Cd concentration was 53% lower than that in the edible parts of plants grown in LS (P1). The decreased Cd concentrations in the P2 beans may be due to the biomass dilution effect. Notably, the Cd concentrations in the beans exceeded the national safety limit value (0.2 mg kg-1) when the Cd treatment levels exceeded 2 mg kg-1 in LS and 6 mg kg-1 in amended LS. The MgCl2 extraction procedures can be used to assess Cd bioavailability in amended soil-plant systems. The potential antagonism of Zn and Cu against Cd toxicity in the soil-plant system may explain why this plant can tolerate higher Cd concentrations after MSC application.

Extramural vascular invasion detected by contrast-enhanced multiple-row detectors computed tomography (ceMDCT) as a predictor of synchronous metastases in colon cancer.

BACKGROUND: Extramural Vascular Invasion (EMVI) is histologically defined as the presence of tumor cells beyond the muscularis propria in vessels resulting in disease metastases. OBJECTIVE: To determine whether EMVI, detected by contrast-enhanced multiple-row detectors computed tomography (MDCT), has closely association with synchronous metastases in colon cancer. METHODS: Patients with pathology proven colon cancer were included in this retrospective study. Preoperative imaging status, including Extramural tumor depth, Lymph nodes, tumor location, and ctEMVI status, were defined on MDCT. Postoperative pathological tumor stage, lymph node stage, and tumor differentiation, were defined in accordance with the American Joint Committee on Cancer (AJCC) 7th Edition. Synchronous metastases were detected on follow-up MDCT 3 months after initial diagnosis or by surgery, if available. Associations between ctEMVI and other preoperative and postoperative factors were analyzed using Chi-squared tests. Logistic regression analyses were performed to analyze the preoperative and postoperative factors of synchronous metastases in colon cancer. RESULTS: ctEMVI was observed in 96 patients (96/241, 39.8%). The presence of ctEMVI varied significantly depending on ctEMD (χ2 = 66.557, P<0.001), lymph nodes status on MDCT (χ2 =24.533, P=0.001), pathological tumor status (χ2 = 36.267, P <0.001) and pathological lymph nodes status analyses (χ2 =32.103, P <0.001). Synchronous metastases were seen in 36 patients (36/96, 37.5%) with ctEMVI and 11 (11/145, 7.6%) patients without ctEMVI. The incidence of synchronous metastases was significantly higher in the cohort of positive ctEMVI with odds ratio (OR) of 7.309 (95% CI 3.485∼15.330, P<0.001). Positive ctEMVI (Odds ratio 4.654, 95%CI: 1.987∼10.898, P <0.001) and ctEMD larger than 5 mm (Odds ratio 2.654, 95%CI: 1.116∼6.309, P =0.027) were demonstrated to be significant preoperative factors in predicting synchronous metastases. CONCLUSION: MDCT-detected EMVI could be used as a preoperative factor to predict synchronous metastases in colon cancer.

Mobile App-Based Interventions to Support Diabetes Self-Management: A Systematic Review of Randomized Controlled Trials to Identify Functions Associated with Glycemic Efficacy.

BACKGROUND: Mobile health apps for diabetes self-management have different functions. However, the efficacy and safety of each function are not well studied, and no classification is available for these functions. OBJECTIVE: The aims of this study were to (1) develop and validate a taxonomy of apps for diabetes self-management, (2) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of randomized controlled trials (RCTs), and (3) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy. METHODS: We developed a 3-axis taxonomy with columns of clinical modules, rows of functional modules and cells of functions with risk assessments. This taxonomy was validated by reviewing and classifying commercially available diabetes apps. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese Biomedical Literature Database, and ClinicalTrials.gov from January 2007 to May 2016. We included RCTs of adult outpatients with diabetes that compared using mobile app-based interventions with usual care alone. The mean differences (MDs) in hemoglobin A1c (HbA1c) concentrations and risk ratios of adverse events were pooled using a random-effects meta-analysis. After taxonomic classification, we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions. RESULTS: Across 12 included trials involving 974 participants, using app-based interventions was associated with a clinically significant reduction of HbA1c (MD 0.48%, 95% CI 0.19%-0.77%) without excess adverse events. Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes (MD 0.67%, 95% CI 0.30%-1.03% vs MD 0.36%, 95% CI 0.08%-0.81%). Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction (with complication prevention: MD 1.31%, 95% CI 0.66%-1.96% vs without: MD 0.38%, 95% CI 0.09%-0.67%; intersubgroup P=.01), as was having a structured display (with structured display: MD 0.69%, 95% CI 0.32%-1.06% vs without: MD 0.16%, 95% CI 0.16%-0.48%; intersubgroup P=.03). However, having a clinical decision-making function was not associated with a larger HbA1c reduction (with clinical decision making: MD 0.18%, 95% CI 0.21%-0.56% vs without: MD 0.61%, 95% CI 0.27%-0.95%; intersubgroup P=.10). CONCLUSIONS: The use of mobile app-based interventions yields a clinically significant HbA1c reduction among adult outpatients with diabetes, especially among those with type 2 diabetes. Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps.

Cancer risk of sulfonylureas in patients with type 2 diabetes mellitus: A systematic review.

BACKGROUND: Increasing evidence suggests that oral hypoglycemic agents used in type 2 diabetes mellitus (T2DM) may affect cancer risk. Sulfonylureas (SUs) are the most frequently used antidiabetic medications for T2DM. Whether using SUs has any effect on cancer has received considerable attention. The aim of this study was to assess the effects of SUs on cancer risk in T2DM patients. METHODS: Published studies were identified in PubMed, EMBASE, and the Cochrane Register of Clinical Studies, and ClinicalTrials.gov was searched for additional information to identify randomized controlled trials (RCTs), cohort studies, and case-control studies. The abstracts and full text were screened, data collected, and the risk of bias assessed for each individual study. RESULTS: Seventy-seven studies (33 RCTs, 27 cohort studies, and 17 case-control studies) were analyzed. The RCTs did not report a difference in the risk of malignant tumor between SU-treated T2DM patients and controls (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.78-1.18); cohort studies showed that cancer risk was higher in patients using SUs than metformin (relative risk 1.60 [95%CI 1.37-1.87]; adjusted hazard ratio 1.13 [95%CI 1.06-1.19]), and case-control studies suggested a trend for increased cancer risk in those using SUs compared with non-SU users (adjusted OR 1.13; 95%CI 0.93-1.37). CONCLUSIONS: The available evidence clearly shows that SUs can significantly increase the risk of cancer compared with metformin. Although the evidence suggests the possibility that SU users may have a higher risk of cancer than those using alternative medications in addition to metformin, it remains inadequate to enable definitive conclusions to be drawn.