MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK

Intestinal-type gastric cancer (GC) of the Lauren classification system has specific epidemiological characteristics and carcinogenesis patterns. MicroRNAs (miRNAs) have prognostic significance, and some can be used as prognostic biomarkers in GC. In this study, we identified miR-1224 as a potential survival-related miRNA in intestinal-type GC patients by The Cancer Genome Atlas (TCGA) analysis. Using quantitative real-time PCR (qRT-PCR), we showed that the relative expression of miR-1224 was significantly decreased in intestinal-type GC tissues compared to matched adjacent normal mucosa tissues (p < 0.01). We found that high miR-1224 expression was associated with no lymph-node metastasis (p < 0.05) and good prognosis (p = 0.028) in 90 intestinal-type GC tissues. Transfection of intestinal-type GC cells with miR-1224 mimics showed that miR-1224 suppressed cell migration in vitro (wound healing assay and Transwell migration assay), whereas the transfection of cells with miR-1224 inhibitor promoted cell migration in vitro. miR-1224 also suppressed intestinal-type GC cell metastasis in a xenograft mouse model. Furthermore, bioinformatics, luciferase reporter, Western blotting, and immunohistochemistry (IHC) studies demonstrated that miR-1224 directly bound to the focal adhesion kinase (FAK) gene, and downregulated its expression, which decreased STAT3 and NF-κB signaling and subsequent the epithelial-to-mesenchymal transition (EMT). Repression of FAK is required for the miR-1224-mediated inhibition of cell migration in intestinal-type GC. The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC

IPDmada: An R Shiny tool for analyzing and visualizing individual patient data meta-analyses of diagnostic test accuracy

Background: Individual patient data meta-analyses (IPD-MA) are regarded as the gold standard for systematic reviews, which also applies to systematic reviews of diagnostic test accuracy (DTA) studies. An increasing number of DTA systematic reviews with IPD-MA have been published in recent years, but there is much variation in how these IPD-MA were performed. A number of existing methods were found, but there is no consensus as to which methods are preferred as the standard methods for statistical analysis in DTA IPD-MA. Objectives: To create a web-based tool which integrates recommended statistical analyses for DTA IPD-MA, and allows researchers to analyse the data and visualize the results with interactive plots. Methods: A systematic methodological review was performed to identify statistical analyses and data visualization methods used in DTA IPD-MA. Methods were evaluated by the authors and recommended analyses were integrated into the IPDmada tool which is freely available online with the user interface developed with R Shiny package. Results: IPDmada allows users to upload their own data, perform the meta-analysis with both continuous and dichotomized tests, and incorporate individual level covariate-adjusted analysis. All tables and figures can be exported as.csv or.pdf files. A hypothetical dataset was used to illustrate the application of IPDmada. Conclusions: IPDmada will be very helpful to researchers doing DTA IPD-MA, since it not only facilitates the statistical analysis but also provides a standard framework. The introduction of IPDmada will harmonize the methods used in DTA IPD-MA and ensure the quality of such analyses. Highlights: IPDmada is a newly developed web-based tool for performing statistical analysis of individual patient data meta-analysis of diagnostic accuracy and visualizing the results. The tool is freely available to all the researchers, and requiring no installation of statistical software/packages. The tool has an user-friendly interface, and allows meta-analysis on both dichotomized and continuous test results. Researchers can easily use this tool to investigate the threshold effect and covariate effect on the summary accuracy. The introduction and implementation of IPDmada will serve as a useful tool for DTA IPD-MA and increase the quality of such studies

Use of Chinese herbal medicines for acute cough in China: an online survey

Introduction: anti-microbial resistance is a complex and evolving global public health threat. Promoting effective alternative treatments is an important way to reduce the unnecessary use of antibiotics. This study aimed to identify the use of treatments for acute cough in China, including Chinese herbal medicines (CHMs) and their association with avoidance of antibiotics and participants’ reported clinical recovery. Methods: an online retrospective treatment outcome survey was conducted. Retrospective clinical information was collected on participants who either were experiencing acute cough, or had experienced acute cough in the last 3 months. Participants were recruited through WeChat (a QR code or a link to the online survey), using snowball sampling. We analysed the usage of different CHMs, changes in symptoms as measured by Likert scales and subsequent use of antibiotics. Results: a total of 25,583 participants completed the online questionnaire, covering all 34 province-level administrative units in China. Respondents had a median age of 25 years (73.5%, aged 18–39). Most respondents reported sputum (65.8%). Nearly half of the participants (45.3%) reported using antibiotics, 39.4% using CHMs, 27.1% and 20.9% using non-antibiotic Western medications and home remedies respectively. Fewer participants took antibiotics after taking CHMs (14.4%), compared to those who started with home remedies (17.6%), or non-antibiotic Western medications (24.5%). The recommendation of doctors (62.4%) and pharmacies (32.1%) were the most common reason for choosing CHMs. Participant-reported clinical recovery was similar (same median of 4 on a 1–5 Likert self-rating scale) regardless of type of CHM. The five CHMs associated with the lowest proportions of subsequent antibiotic use were individualised Chinese herbal formulae, Xiao Qing Long granule, Xian Zhu Li liquid, Chuan Bei Pi Pa Gao and Shi Wu Wei Long Dan Hua pill. The most commonly used herbs in the Chinese patent medicines were Glycyrrhizae radix et rhizome, Platycodonis radix, Pinelliae rhizome, Armeniacae semen amarum, Ephedrae herba, and Citri reticulatae pericarpium. Conclusion: almost 40% of participants with acute cough used CHMs. The proportion of participants who subsequently used antibiotics after CHMs was lower than other treatments. CHMs have a potential role for symptom relief thus reducing antibiotic use.</p

Use of Chinese herbal medicines with acute cough in China: an online survey

Introduction: anti-microbial resistance is a complex and evolving global public health threat. Promoting effective alternative treatments is an important way to reduce the unnecessary use of antibiotics. This study aimed to identify the use of treatments for acute cough in China, including Chinese herbal medicines (CHMs) and their association with avoidance of antibiotics and participants’ reported clinical recovery.Methods: an online retrospective treatment outcome survey was conducted. Retrospective clinical information was collected on participants who either were experiencing acute cough, or had experienced acute cough in the last 3 months. Participants were recruited through WeChat (a QR code or a link to the online survey), using snowball sampling. We analysed the usage of different CHMs, changes in symptoms as measured by Likert scales and subsequent use of antibiotics.Results: a total of 25,583 participants completed the online questionnaire, covering all 34 province-level administrative units in China. Respondents had a median age of 25 years (73.5%, aged 18–39). Most respondents reported sputum (65.8%). Nearly half of the participants (45.3%) reported using antibiotics, 39.4% using CHMs, 27.1% and 20.9% using non-antibiotic Western medications and home remedies respectively. Fewer participants took antibiotics after taking CHMs (14.4%), compared to those who started with home remedies (17.6%), or non-antibiotic Western medications (24.5%). The recommendation of doctors (62.4%) and pharmacies (32.1%) were the most common reason for choosing CHMs. Participant-reported clinical recovery was similar (same median of 4 on a 1–5 Likert self-rating scale) regardless of type of CHM. The five CHMs associated with the lowest proportions of subsequent antibiotic use were individualised Chinese herbal formulae, Xiao Qing Long granule, Xian Zhu Li liquid, Chuan Bei Pi Pa Gao and Shi Wu Wei Long Dan Hua pill. The most commonly used herbs in the Chinese patent medicines were Glycyrrhizae radix et rhizome, Platycodonis radix, Pinelliae rhizome, Armeniacae semen amarum, Ephedrae herba, and Citri reticulatae pericarpium.Conclusion: almost 40% of participants with acute cough used CHMs. The proportion of participants who subsequently used antibiotics after CHMs was lower than other treatments. CHMs have a potential role for symptom relief thus reducing antibiotic use

Engineered magnetosomes fused to functional molecule (protein A) provide a highly effective alternative to commercial immunomagnetic beads

Abstract Background Magnetosomes (also called bacterial magnetic nanoparticles; BMPs) are biomembrane-coated nanoparticles synthesized by magnetotactic bacteria (MTB). Engineered BMPs fused to protein A (termed ∆F-BMP-FA) bind antibodies (Abs) automatically, and thus provide a series of potential advantages. However, no report so far has systematically evaluated functional applicability of genetically engineered BMPs. Results We evaluated properties of ∆F-BMP-FA, and developed/optimized culture methods for host strain Magnetospirillum gryphiswaldense ΔF-FA, ∆F-BMP-FA extraction conditions, conditions for Ab conjugation to ∆F-BMP-FA surface, and procedures for antigen detection using ∆F-BMP-FA/Ab complexes (termed BMP-A-Ab). Fed-batch culture for 36 h in a 42-L fermentor resulted in yields (dry weight) of 2.26 g/L for strain ΔF-FA and 62 mg/L for ∆F-BMP-FA. Optimal wash cycle number for ∆F-BMP-FA purification was seven, with magnetic separation following each ultrasonication step. Fusion of protein A to BMPs resulted in ordered arrangement of Abs on BMP surface. Linkage rate 962 μg Ab per mg ∆F-BMP-FA was achieved. BMP-A-Ab were tested for detection of pathogen (Vibrio parahaemolyticus; Vp) surface antigen and hapten (gentamicin sulfate). Maximal Vp capture rate for BMP-A-Ab was 90% (higher than rate for commercial immunomagnetic beads), and detection sensitivity was 5 CFU/mL. ∆F-BMP-FA also bound Abs from crude mouse ascites to form complex. Lowest gentamicin sulfate detection line for BMP-A-Ab was 0.01 ng/mL, 400-fold lower than that for double Ab sandwich ELISA, and gentamicin sulfate recovery rate for BMP-A-Ab was 93.2%. Conclusion Our findings indicate that engineered BMPs such as ∆F-BMP-FA are inexpensive, eco-friendly alternatives to commercial immunomagnetic beads for detection or diagnostic immunoassays, and have high Ab-conjugation and antigen-adsorption capacity

Evidence base of randomized controlled trials and guideline recommendations of patent Traditional Chinese Medicines for uncomplicated acute lower respiratory tract infections in adults

OBJECTIVE: To compare clinical practice guideline recommendations on the use of oral patent Traditional Chinese Medicines (PTCMs) for uncomplicated acute lower respiratory tract infections (ALRTIs) in adults with the existing evidence using results of a systematic review of randomized controlled trials (RCTs). METHODS: A systematic review on RCTs and a systematic review of current guidelines on orally taken PTCMs for uncomplicated ALRTIs were performed. PubMed, Cochrane Library, EMBASE and four Chinese databases were searched from inception to September 2016 for RCTs testing orally taken PTCMs for uncomplicated ALRTIs (excluding pneumonia). Two reviewers independently screened each study, extracted study data, and assessed risk of bias. Disagreements were resolved through discussion or by consultation with a third reviewer. Clinical practice guidelines for uncomplicated ALRTIs containing PTCM recommendations were identified and quality appraised. The quality of pooled evidence of the RCTs and the guidelines was assessed with GRADE and AGREE � respectively. The consistency of the evidence base in RCTs and the guideline recommendations were then compared. RESULTS: For the systematic review of RCTs, 4810 papers were identified, among which 29 RCTs (5093 patients) were included in the review. PTCMs compared to placebo increased the effective treatment rate of cough (3 trials, 949 patients, risk ratio (RR) 2.50, 1.16 to 5.43; low certainty); improved assessment of global health (3 trials, 948 patients, RR 1.70, 1.44 to 2.01; low certainty); and increased the effective rate of specific symptom relief (1 trial, 478 patients, RR 4.01, 2.76 to 5.81; moderate certainty). 21 trials (3432 patients) compared effects of different PTCMs. For the guideline evaluation, 29 PTCMs were recommended for the use of uncomplicated ALRTIs, of which27 had no supportive evidence from RCTs. CONCLUSION: The evidence base of PTCMs for uncomplicated ALRTIs is weak and the guideline recommendations were based on almost no clinical trial evidence. Rigorous clinical research is urgently needed to inform the clinical use of these herbal medicines. Further training in evidence-based medicine methods for Traditional Chinese Medicine guideline developers is essential.</p

Shufeng Jiedu capsules for treating acute exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis

Background: Chinese herbal medicine is widely used in combination with usual care for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in China. Shufeng Jiedu capsule (SFJD) is a Chinese patent medicine. The effectiveness and safety of SFJD for AECOPD remains uncertain.Methods: A systematic review of randomized control trials was performed. We included trials in patients diagnosed with AECOPD, who received SFJD as a single intervention or in combination with usual treatment. PubMed, Cochrane Library, EMBASE, CINAHL and four Chinese databases were searched from inception to April 2019. Two reviewers independently screened studies, extracted study data and assessed risk of bias. Meta-analysis was performed using RevMan 5.3 software. We performed subgroup analyses and sensitivity analyses according to the predefined protocol. Quality of evidence was assessed using GRADE.Results: 13 RCTs (1,036 patients, of which 936 were inpatients) were included. The mean age ranged from 52 to 67 and approximately 60% of patients were male. These RCTs had a high risk of bias due to lack of blinding and other factors. SFJD combined with usual care (including antimicrobials) compared to usual care alone was associated with a significant reduction in treatment failure, from 20.1% to 8.3% (11 trials; 815 patients; relative risk 0.43, 95% confidence interval [CI] 0.30 to 0.62) and duration of hospital admission (2 trials; 79 patients; mean difference -4.35 days, 95% CI -5.28 to -3.43 days; low certainty ). Low or very low certainty evidence suggested benefit from SFJD compared to controls in terms of PaCO2, PaO2, FEV1/FVC ratio, clinical symptoms, white cell counts, inflammatory markers and health related quality of life. No significant difference in adverse events was found in a pooled analysis. Conclusion: For hospitalized adults with AECOPD, SFJD may reduce treatment failure, shorten hospital stay, and improve symptoms and signs. However, the quality of the evidence is very low to low due to the potential risk of bias and inconsistency among included trials. Further large, high quality RCTs are needed

Acupuncture techniques for COPD: a systematic review

Background This is the second part of a large spectrum systematic review which aims to identify and assess the evidence for the efficacy of non-pharmacological acupuncture techniques in the treatment of chronic obstructive pulmonary disease (COPD). The results of all techniques except for filiform needle are described in this publication. Methods Eleven different databases were screened for randomised controlled trials up to June 2019. Authors in pairs extracted the data and assessed the risk of bias independently. RevMan 5.3 software was used for the meta-analysis. Results Thirty-three trials met the inclusion criteria, which involved the follow techniques: AcuTENS (7 trials), moxibustion (11 trials), acupressure (7 trials), ear acupuncture (6 trials), acupressure and ear acupuncture combined (1 trial) and cupping (1 trial). Due to the great heterogeneity, only 7 meta-analysis could be performed (AcuTENS vs sham on quality of life and exercise capacity, acupressure vs no acupressure on quality of life and anxiety and ear acupuncture vs sham on FEV1 and FEV1/FVC) with only acupressure showing statistical differences for quality of life (SMD: -0.63 95%CI: − 0.88, − 0.39 I2 = 0%) and anxiety (HAM-A scale MD:-4.83 95%CI: − 5.71, − 3.94 I2 = 0%). Conclusions Overall, strong evidence in favour of any technique was not found. Acupressure could be beneficial for dyspnoea, quality of life and anxiety, but this is based on low quality trials. Further large well-designed randomised control trials are needed to elucidate the possible role of acupuncture techniques in the treatment of COPD

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs

Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation