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Introduction Prostate cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of cancer-related death in males in the United States. Despite the initial efficacy of androgen deprivation therapy in prostate cancer (PCa) patients, most patients progress to castration-resistant prostate cancer. However, the mechanisms underlying the androgen-independent progression of PCa remain largely unknown. Methods In this study, we established a PCa cell line (LNCaP-AI) by maintaining LNCaP cells under androgen-depleted conditions. To explore the cellular and molecular mechanisms of androgen-independent growth of PCa, we analyzed the gene expression patterns in androgen-independent prostate cancer (AIPC) compared with that in androgen-dependent prostate cancer (ADPC). KEGG pathway analysis revealed that Wnt signaling pathways were activated after androgen deprivation therapy (ADT). In vitro experiments showed that the inhibition of Wnt pathway reduced AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. Furthermore, WNT5A, LEF1 were identified as direct targets of AR by chromatin immunoprecipitation (ChIP) assay and public ChIP-seq datasets analysis. Results In the present study, we found a regulatory mechanism through which crosstalk between androgen receptor (AR) and Wnt signals promoted androgen-independent conversion of PCa. The Wnt pathway was inhibited by androgen in androgen-dependent prostate cancer cells, but this blocking effect was not elicited in androgen-independent prostate cancer (AIPC) cells. Moreover, Wnt pathway genes WNT5A and LEF1 were directly downregulated by AR. In vitro experiments showed that inhibition of the Wnt pathways repressed AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. We found that WNT5A and LEF1 were downregulated in low-grade PCa but upregulated in metastatic PCa. Conclusion In summary, we revealed that crosstalk between AR and Wnt signaling pathways promotes androgen-independent growth of PCa, which may provide novel therapeutic opportunities for castration-resistant prostate cancer.

This study aimed to evaluate the impact of updated pediatric hypertension (HTN) criteria (the 2017 AAP Guidelines) on prevalence estimates of HTN and prehypertension among Chinese children compared to the 2004 Fourth Report. A total of 2093 children aged 7-15 years from five schools in Tianjin, China were selected using a multistage random cluster sampling method. The prevalence of HTN per the 2017 AAP Guidelines (10.1%) was significantly higher than that per the Fourth Report (6.6%), whereas the prevalence of prehypertension per the 2017 AAP Guidelines (6.3%) was significantly lower than that per the Fourth Report (8.8%). From the 2004 Fourth Report to the 2017 AAP Guidelines, a total of 117 (5.6%) children were reclassified to have higher blood pressure. The two criteria had better consistency in the diagnosis of systolic abnormalities than in the diagnosis of diastolic abnormalities. The updated definitions for pediatric HTN have a substantive impact on the prevalence estimation among Chinese children, especially among boys, overweight children, and older children.

Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up‐regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up‐regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock‐down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR‐29a‐3p sponge to up‐regulate SLC25A15 expression by bioinformatics analysis, dual‐luciferase reporter assays and biotinylated RNA pull‐down assays. SLC25A15 could reverse the tumour suppressing roles of knock‐down circFOXO3 in PCa. Of note, we found that miR‐29a‐3p was down‐regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR‐29a‐3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up‐regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.

BACKGROUND Long noncoding RNA (lncRNA) plays a vital role in the development of many diseases. The abnormal expression of lncRNA is closely related to the occurrence and development of different kinds of tumors including prostate cancer (PCa). METHODS Differentially expressed lncRNA LINC00304 was identified using a publicly available gene expression data set (GSE38241) and quantitative polymerase chain reaction validation. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to predict the molecular function of LINC00304. A lncRNA microarray, bioinformatic analysis, and chromatin immunoprecipitation assay were carried out to verify the upstream androgen receptor (AR) signaling pathway. Subsequently, the function of LINC00304 was observed by a series of in vitro assays. RESULTS We observed higher expression of LINC00304 in PCa cells and samples compared with normal prostate cells and tissues. Functional analysis of LINC00304 showed it was related to regulating cell cycle process, cellular developmental process, and focal adhesion. Further, we identified androgen-inhibited lncRNA, LINC00304 as a direct target of AR. A series of functional studies revealed that overexpression of LINC00304 could significantly promote cell proliferation and cell cycle progression in PCa cells. We also find that LINC00304 can significantly promote CCNA1 expression in PCa cells. CONCLUSIONS Our results indicate that LINC00304 may represent a new diagnostic and therapeutic biomarker for PCa.

Background The purpose of this study was to screen the predictive factors of no-reflow after a percutaneous coronary intervention (PCI) in elderly patients with ST-segment elevation myocardial infarction (STEMI), and to construct a nomogram model, to guide clinical treatment. Methods A total of 551 elderly STEMI patients (age >65) underwent direct PCI were randomly classified into training group (n=386, 70%) and validation group (n=165, 30%). All patients in the two groups were divided into a no-reflow group and a normal blood flow group according to whether there was a no-reflow phenomenon. Univariable and multivariable logistic regression analysis was used to analyze the relevant data, including demographic characteristics, clinical characteristics, coronary angiography results, electrocardiogram (ECG) results, and biochemical indicators. Then, a nomogram model was constructed on the screened risk factors. The performance of the nomogram was evaluated in terms of discrimination and calibration. The nomogram was further confirmed in the internal validation group. Additionally, decision curve analysis (DCA) was applied to assess the clinical usefulness of the nomogram. Results Five remarkable risk factors were determined: preoperative TIMI blood flow, the diameter of the target lesion, collateral circulation, pulse pressure, and the number of leads for ST-segment elevation. The nomogram involving these five risk factors showed full calibration and discrimination in the training group, with an AUC of 0.71 (95% CI: 0.66-0.77). It was confirmed in the validation group, and the entire cohort and the AUC were 0.64 (95% CI: 0.56-0.73) and 0.69 (95% CI: 0.65-0.74), respectively. Whether in the training group or the verification group, the calibration curve for the probability of no-reflow phenomenon all showed considerable consistency between prediction by nomogram and actual observation. The decision curve revealed a specific role in our nomogram in clinical practice. Conclusions We set up a nomogram that showed absolute accuracy for the prediction of the risk of no-reflow after primary PCI in elderly STEMI patients.

Background Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort. Methods Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis- and trans-regulations by long noncoding RNAs. Interactions between transcription factors and long noncoding RNAs were validated by RNA immunoprecipitation quantitative PCR. RNA interference assays were performed to explore roles of the selected transcription regulators. Findings Sixteen transcription factors, namely, ETS1, ARID4B, KLF12, GMEB1, HBP1, MXI1, MYC, MAX, PGR, BCL11A, AR, KLF4, SRF, HIF1A, EHF, and ATOH1, were jointly identified as a prognostic signature. Candidate long noncoding RNAs interplaying with the prognostic signature constituent transcription factors were further discovered. Their interactions were randomly checked, and many of them were experimentally proved. Transcription regulation by MYC and its long noncoding RNA partner AL590617.2 was further validated on their candidate targets. Moreover, the regulatory network governed by the transcription factors and their interacting long noncoding RNA partners is illustrated and stored in our LNCTRN database ( https://navy.shinyapps.io/lnctrn ). Interpretation The prognostic signature constituent transcription factors and their interacting long noncoding RNAs may represent promising biomarkers and/or therapeutic targets for prostate cancer. Furthermore, the computational framework proposed in the present study can be utilized to explore critical transcriptional regulators in other types of cancer. Funding This work was supported by National Natural Science Foundation of China and Fudan University.

To characterize the prevalence of hypertension and prehypertension and its association with four anthropometrics among children aged 7–15 years in Tianjin, China, a school-based cross-sectional survey was conducted from May to August 2010. Multistage random cluster sampling was used to select the participants. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) were measured. Hypertension and prehypertension were identified according to the definition of United State Fourth Report. Logistic regression, linear regression and the area under receiver operating curves (AUC) was used for assessing the association. Among 1898 eligible children, the prevalence of hypertension and prehypertension was 6% and 6.6%, respectively. No statistically significant differences were found between boys and girls. Both linear and logistic regression showed that the four anthropometrics were all positively related to blood pressure value or the risk of prehypertension and hypertension. Of the four anthropometrics, BMI might be the most sensitive indicator for predicting elevated blood pressure, followed by WC and WHtR, whereas WHR had the lowest predicting capacity, with the AUCs being 0.72 (0.68,0.75), 0.69 (0.65,0.73), 0.67 (0.63,0.71), and 0.61 (0.57,0.65), respectively. A significantly increased prevalence of hypertension was observed when BMI > P90 percentiles, but for prehypertension, the risk of prehypertension began to increase when BMI was still at a median level. In conclusion, four anthropometrics all had positive relationship with elevated blood pressure. BMI and WC were superior to WHtR and WHR in predicting elevated blood pressure among children and adolescents.

Background. Appreciable findings have pointed out pivotal roles of N6-methyladenosine (m6A) machinery in cancer onset and progression. However, limited efforts have been directed towards relevant research in the prostate cancer area. Methods. A PubMed search was conducted to acquire components of the mRNA m6A machinery. Multiomics integration was performed to systematically investigate the mRNA m6A machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic m6A readers EIF3D and HNRNPA2B1 were conducted to explore m6A dependence of their functions in prostate cancer cell proliferation and migration. Results. A total of 41 mRNA m6A regulators have been identified to date. A small degree of copy number aberrations and an extremely low frequency of somatic mutations were observed in the regulators across prostate tumors. Enrichment of CpG sites and extensive changes of DNA methylation in the m6A machinery were also found. Impact of copy number variation on m6A regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of m6A regulators related to clinical features and/or survival which were largely m6A-binding proteins. The translation initiation factor subunit EIF3D and the splicing factor HNRNPA2B1 can be independent prognostic factors which may contribute to retardation and promotion of cancer progression, respectively, through affecting cancer-related processes such as cell cycle. Moreover, in vitro assays demonstrated that m6A impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells. Conclusions. Our report systematically described molecular features of the mRNA m6A machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the m6A system in prostate cancer.

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.

No-reflow is an important complication among patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A retrospective study of 1658 STEMI patients undergoing direct PCI was performed. Patients were randomly assigned at a 7:3 ratio into development cohort and validation cohort and into no-reflow and normal blood flow groups. Clinical data and laboratory examinations were compared to identify independent risk factors and establish a no-reflow risk scoring system. In the development cohort (n = 1122), 331 (29.5%) had no-reflow. Multivariate analysis showed age ≥ 65 years (OR = 1.766, 95% confidence interval (CI): 1.313–2.376, P 8 mmol/L (OR = 1.386, 95%CI: 1.007–1.908, P = .045) were related to no-reflow. Receiver operating characteristic (ROC) area under the curve was 0.648 (95%CI: 0.609–0.86). At 0.349 cutoff sensitivity was 42.0%, specificity was 79.3%, positive predictive value (PPV) was 44.7%, negative predictive value (NPV) was 77.4%, P

Recombinant influenza Virus-Like Particle (VLP) vaccines are promising vaccine candidates to prevent influenza, contain two major viral antigenic glycoproteins, Hemagglutinin (HA) and Neuraminidase (NA), on the surface of recombinant VLPs. Accurate quantitation of the mass of these antigenic proteins is important to ensure the product quality and proper dosing. Currently, Single Radial Immunodiffusion (SRID) is a recognized assay for determination of the HA immuno-reactive concentration (potency) in vaccine products, based on immuno-reactivity of HA with strain-specific antisera. The SRID assay, however, requires availability of strain-specific and properly calibrated reagents, which can be time-consuming to generate and calibrate. In addition, the assay is not suitable for quantitation of low abundant proteins, such as NA. In order to accelerate the overall production cycle, we have developed and optimized a high-resolution (HR) LC-MS method for absolute quantitation of both HA and NA protein concentrations in influenza VLP vaccine candidates. In this work, we present the method development, optimization and verification of its suitability for the intended purpose, as a prerequisite for its potential application in Quality Control, by assessing specificity, precision and accuracy, detection characteristics, and dynamic linear range. The method can be also used for other HA/NA containing preparations including in-process samples, purified proteins, whole virus preparations, nano-particle and egg-based vaccine preparations, or for calibration of SRID reference antigens.

Background Prostate cancer (PCa) is one of the most common cancers in males in China. Long noncoding RNAs (lncRNAs) reportedly play crucial roles in human cancer progression in many studies. However, the molecular mechanisms underlying PCa progression remain unclear. Materials and methods We investigated the lncRNA transcriptome using publicly available RNA-sequencing data to identify prostate-specific lncRNAs. Then, the chromatin immunoprecipitation (ChIP) assay identified lncRNA with a direct binding to androgen receptor (AR), hereafter denoted as PSLNR. Quantitative real-time polymerase chain reaction analysis and Western blot analysis were performed to detect the expression of p53 signaling-related genes after overexpression PSLNR. The effects of overexpression of PSLNR on cell proliferation, cell cycle, and cell apoptosis were assessed by using CCK-8 and flow cytometric analysis. We then detected the expression of PSLNR in tissues. Result We reported a novel androgen-reduced prostate-specific lncRNA, PSLNR, that inhibited PCa progression via the p53-dependent pathway. By analyzing the NOCODE data set, we reported that PSLNR was specifically expressed in the prostate, suggesting the potential of PSLNR as a biomarker for PCa treatment. The AR pathway was also confirmed to be an upstream regulation signaling pathway of PSLNR by transcriptionally regulating its expression in androgen-dependent PCa cells. PSLNR also significantly inhibited PCa proliferation by inducing cell apoptosis in a p53-dependent manner. Thus, PSLNR may be a candidate diagnosis and therapeutic target for PCa. Conclusions Our study revealed for the first time a novel androgen-reduced prostate-specific lncRNA, PSLNR, which inhibited PCa progression via the p53-dependent pathway, suggesting that PSLNR may be a candidate diagnosis and therapeutic target for PCa.

Background: Recently, immune checkpoint inhibitors (ICIs) have been proved one of the most promising anti-cancer therapy, series clinical trials have confirmed their efficacy. But they are also associated with distinctive set of toxic effects, which are recognized as immune-related adverse events. Among those immune-related adverse events, pneumonitis is rare, but it is often clinically serious and potentially life-threatening. Although many clinical trial results of PD-1/PD-L1 inhibitors had been reported incidence of pneumonitis, the knowledge based on the individual cohort data from each clinical trial is limited. So we conducted a meta-analysis of trials of PD-1/PD-L1 inhibitors in patients with advanced cancer and compared relative risk and incidence among different tumor types and therapeutic regimens. Such an analysis may provide important knowledge of this rare but clinically significant and potentially serious immune-related adverse event.Methods: Electronic databases were used to search eligible literatures, include randomized controlled trials (RCTs) comparing immune checkpoint inhibitors vs. standard therapies. All-grade (1–4) or high-grade (3–4) pneumonitis events were extracted. The summary relative risk, summary incidence, and 95% confidence intervals were calculated.Results: The incidence of all-grade and high-grade pneumonitis in non-small cell lung cancer (NSCLC) was significantly higher compared with other tumor types, such as Melanoma, urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC) (3.1% vs. 2.0%; p = 0.02, 1.4% vs. 0.6%; p = 0.03). The risk of all-grade pneumonitis was obtained from all patients in both experimental arm and control arm. Treatment with immune checkpoint inhibitors targeting PD-1/PD-L1 did significantly increase the risk of all-grade and high-grade pneumonitis compared with controls (fixed effects, RR: 4.70; 95% CI: 2.81–7.85; p < 0.00001, RR: 3.33; 95% CI: 1.68–6.59; p = 0.0006).Conclusion: The incidence of immune checkpoint inhibitors related pneumonitis was higher in NSCLC than other tumor types. Patients treated with immune checkpoint inhibitor in experiment arms are more likely to experience any grade pneumonitis than control arms. These findings suggest that clinician need to draw more attention on this rare but serious adverse event.