Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR-625 and miR-892b.

Circular RNAs (circRNAs) have been regarded as critical regulators of human diseases and biological markers in some types of malignancies, including pancreatic ductal adenocarcinoma (PDAC). Recently, circ_0007534 has been identified as a novel cancer-related circRNA. Nevertheless, its clinical relevance, functional roles, and mechanism have not been studied in PDAC. In the current study, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of circ_0007534 in 60-paired PDAC tissue samples and different cell lines. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, and metastatic properties affected by circ_0007534. An animal study was also carried out. The luciferase reporter assay was performed to uncover the underlying mechanism of circ_0007534. As a result, circ_0007534 was overexpressed not only in PDAC tissues but also in a panel of PDAC cell lines, and this overexpression is closely associated with advanced tumor stage and positive lymph node invasion. In addition, circ_0007534 may be regarded as an independent prognostic factor for patients with PDAC. For the part of functional assays, circ_0007534 significantly increased cell proliferation, migratory, and invasive potential of PDAC cells. Circ_0007534 could inhibit cell apoptosis partly via a Bcl-2/caspase-3 pathway. The xenograft study further confirmed the cell growth promoting the role of circ_0007534. Mechanistically, miR-625 and miR-892b were sponged by circ_0007534. The oncogenic functions of circ_0007534 is partly dependent on its regulation of miR-625 and miR-892b. In conclusion, our study illuminates a novel circRNA that confers an oncogenic function in PDAC.

Prognostic implication of systemic inflammatory state on antiplatelet effect in patients after percutaneous coronary intervention for ST-elevation myocardial infarction: A retrospective cohort study.

ABSTRACT: Patients with ST-elevation myocardial infarction (STEMI) show an inflammatory response. The level of systemic inflammation is known to affect platelet aggregation function and antiplatelet therapy, which leads to different clinical prognosis. This study aims to evaluate the prognostic implication of systemic inflammatory state in patients with STEMI undergoing percutaneous coronary intervention.In this study, 203 patients with STEMI who underwent primary percutaneous coronary intervention were included. The patients were divided into 3 groups based on the inflammation levels assessed by tertiles of high-sensitivity C-reactive protein (hs-CRP) level on admission. Platelet aggregation evaluation was performed by residual platelet reactivity, which was assessed by the value of residual ADP-induced light transmittance aggregometry after clopidogrel maintenance dose therapy and in follow-up. Major adverse cardiac events (MACEs) were defined to include all-cause mortality, cardiovascular mortality, reinfarction, target vessel revascularization (TVR), cardiopulmonary resuscitation, advanced heart failure, ventricular fibrillation or ventricular tachycardia, and atrioventricular block.Levels of white blood cell was observed to be significantly higher at high tertile levels. Residual ADP-induced platelet aggregation was significantly higher at high tertile levels after clopidogrel maintenance dose therapy and in follow-up. Multivariate analysis identified that reperfusion time, alanine aminotransferase, platelet count, ADP-induced light transmittance aggregometry in follow-up and hs-CRP was independent predictors of MACEs. Platelet inhibition function of clopidogrel decreases progressively at different inflammation levels. The different levels of hs-CRP were demonstrated to be associated with MACEs at follow-up assessments.The presence of hs-CRP was not only significantly associated with platelet inhibition function, but was also a prognostic marker in STEMI.

Novel GLP-1/anti-apolipoprotein B bifunctional fusion protein alleviates diabetes and diabetic complications in combination with low-intensity ultrasound.

AIMS: To engineer and screen a novel GLP-1/anti-apolipoprotein B (apoB) bifunctional fusion protein with therapeutic potential on alleviating diabetes and diabetic complication in combination with low-intensity ultrasound. MAIN METHODS: Anti-apoB antibodies were screened by phage display technology and further fused to mutated GLP-1 (7-37) via light or heavy fusion to generate bifunctional fusion protein (termed aBG). The optimal design of aBG fusion protein was further confirmed by in vitro epitope competition assay and cAMP accumulation assay. Subsequently, chronic study in DIO mice were subjected to assess the long-term efficacy of screened fusion protein. KEY FINDINGS: The selected GLP-1/anti-apoB fusion protein, aBG-8, exerted either the highest binding affinities for GLP-1R and apoB, or the greatest LDL-C uptake capacity and GLP-1R activation activity. After 60-day treatment in DIO mice, aBG-8 was proved to exert the promising improvement on hyperglycemia, hyperlipidemia, and obesity in DIO mice. Furthermore, combined therapy of aBG-8 and low-intensity ultrasound could accelerate skin wound closure in diabetic mice. SIGNIFICANCE: A novel long-lasting bifunctional fusion molecule, aBG-8, was designed with the enormous potential on alleviating diabetes and diabetic complications in combination with low-intensity ultrasound.

Synergic fabrication of pembrolizumab loaded doxorubicin incorporating microbubbles delivery for ultrasound contrast agents mediated anti-proliferation and apoptosis.

This study evaluated pembrolizumab-conjugated, doxorubicin (DOX)-loaded microbubbles (PDMs) in combination with ultrasound (US) as molecular imaging agents for early diagnosis of B cell lymphomas, and as a targeted drug delivery system. Pembrolizumab, a monoclonal CD20 antibody, was attached to the surfaces of DOX-loaded microbubbles. PDM binding to B cell lymphoma cells was assessed using immunofluorescence. The cytotoxic effects of PDMs in combination with ultrasound (PDMs + US) were evaluated in vitro in CD20+ and CD20- cell lines, and its antitumor activities were assessed in Raji (CD20+) and Jurkat (CD20-) lymphoma cell-grafted mice. PDMs specifically bound to CD20+ cells in vitro and in vivo. Contrast enhancement was monitored in vivo via US. PDM peak intensities and contrast enhancement durations were higher in Raji than in Jurkat cell-grafted mice (p < 0.05). PDMs + US treatment resulted in improved antitumor effects and reduced systemic toxicity in Raji cell-grafted mice compared with other treatments (p < .05). Our results showed that PDMs + US enhanced tumor targeting, reduced systemic toxicity, and inhibited CD20+ B cell lymphoma growth in vivo. Targeted PDMs could be employed as US molecular imaging agents for early diagnosis, and are an effective targeted drug delivery system in combination with US for CD20+ B cell malignancy treatment.

Evaluation of 3D-CEUS in the Recurrence of Liver Cancer after Radiofrequency Ablation.

Background: Radiofrequency ablation (RFA) has the similar curative effects to surgery, but RFA will lead to higher postoperative local recurrence rate. 3D-CEUS is a minimally invasive examination method, which is used to analyze the sensitivity to postoperative recurrence in this study. Methods: The clinical data of 60 patients with liver cancer admitted to our hospital (February 2018-February 2020) were retrospectively analyzed. All patients were treated with RFA and were followed up with 3D-CEUS, MRI, and enhanced CT examination after surgery. The ROC curve was used to analyze the differences of different examination methods in judging postoperative recurrence. Results: For the 60 patients, 52 patients (86.7%) had a single lesion and 8 patients (13.3%) had multiple lesions, with a total of 72 lesions. After RFA, 56 lesions (77.8%) were completely inactivated and 16 lesions (22.2%) remained. Totally inactivated lesions were detected as follows: 51 (91.1%) by 3D-CEUS, 42 (75.0%) by MRI, and 50 (89.3%) by enhanced CT. During a 2-year follow-up, a total of 26 recurrent lesions were detected, 24 (92.3%) by 3D-CEUS, 12 (46.2%) by MRI, and 25 (96.2%) by enhanced CT, indicating that the sensitivity of 3D-CEUS and enhanced CT was obviously higher than that of MRI (P < 0.001), without conspicuous difference between sensitivity of 3D-CEUS and enhanced CT (P > 0.05). Conclusion: As a new imaging examination method based on artificial intelligence, 3D-CEUS has a high sensitivity in patients with liver cancer who underwent RFA, which can effectively judge the recurrence after surgery and should be widely used in practice.

Identification of heterogeneous nuclear ribonucleoprotein as a candidate biomarker for diagnosis and prognosis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high mortality rate. However, spliceosomal genes are still lacking in the diagnosis and prognosis of HCC. METHODS: Identification of differentially expressed genes (DEGs) was performed using the limma package in R software. Modules highly related to HCC were obtained by weighted gene co-expression network analysis (WGCNA), and the module genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The biomarker for diagnosing HCC was determined by receiver operating characteristic (ROC) curve analysis, and the effect of the biomarker in the diagnosis of HCC was evaluated by performing five-fold cross-validation with logistic regression. HCC specimens from preoperatively treated patients were tested for biomarker by real-time quantitative polymerase chain reaction (RT-qPCR). Kaplan-Meier analysis was used to assess the relationship between biomarker and patient survival. The role of biomarker was evaluated using ESTIMATE analysis in the tumor microenvironment. RESULTS: In this study, 389 DEGs were screened out from three Gene Expression Omnibus (GEO) datasets. We also found that the turquoise module of 123 genes from The Cancer Genome Atlas (TCGA) data was the key module with the highest correlation with HCC traits. Then, 123 genes were analyzed using the KEGG enrichment pathway, and eight genes were found to be most significantly related to the spliceosome pathway. We selected 8 genes and 389 DEGs shared genes, and finally got the only gene, heterogeneous nuclear ribonucleoprotein (hnRNPU). The high expression of hnRNPU was associated with poor prognosis of HCC, and hnRNPU was a biomarker for diagnosing HCC. In the tissues of patients with excellent HCC treatment hnRNPU messenger RNA (mRNA) was lower than in the tissues of patients with poor HCC treatment. High expression of hnRNPU was significantly increased in HCC patients with low stromal (P<0.05), low immune (P<0.05), and low estimation scores (P<0.05), and with high tumor purity (P<0.05) and high malignant progression (P<0.05) of the HCC. CONCLUSIONS: The hnRNPU gene identified in this study may become a new biomarker for the diagnosis and prognosis of HCC.

Health Literacy and Disparities in Knowledge, Attitude and Practice Regarding COVID-19 Among College Students During the COVID-19 Outbreak in China: A Cross-Sectional Study.

PURPOSE: This study aimed to assess the knowledge, attitude and practice (KAP) towards COVID-19 of Chinese college students during the COVID-19 outbreak and identify the determinants considerably associated with KAP. METHODS: An online cross-sectional questionnaire survey was conducted in February 2020 in China to recruit participants on the Wen-Juan-Xing online platform. A self-made questionnaire was used to assess the KAP towards COVID-19. RESULTS: The average scores of COVID-19-related KAP among college students were 32.16 ± 4.09, 16.84 ± 3.18 and 15.36 ± 1.83, respectively. The average correct response rate of COVID-19-related knowledge was 84.62%. 94.59% of the respondents believed China could control and conquer the pandemic; 98.92% of the respondents wore a mask when they went out. The multiple linear regression showed that the female students had higher scores of COVID-19-related knowledge than male students (ß = 0.79, P = 0.01), and the students from 985 or 211 universities (ß = -2.22, P < 0.01) were significantly associated with higher knowledge scores. Furthermore, a significantly positive correlation was found between the scores of COVID-19-related KAP among students. CONCLUSION: The college students had a good KAP towards the COVID-19 pandemic. The present study was able to access the COVID-19-related KAP among college students during the pandemic and identify their weaknesses in pandemic prevention. Consequently, the results of this study provide theoretical basis for implementing precision health education among college students and reference for campuses to conduct scientific prevention and control during a pandemic. Results also provide beneficial experience to curb similar major public health emergencies in the future.