The pandemic coronavirus SARS-CoV-2 in the world has caused a large infected population suffering from COVID-19. To curb the spreading of the virus, WHO urgently demanded an extension of screening and testing; thus, a rapid and simple diagnostic method is needed. We applied a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) to achieve the detection of SARS-CoV-2 in 30 min. We designed four sets of LAMP primers (6 primers in each set), targeting the viral RNA of SARS-CoV-2 in the regions of orf1ab, S gene and N gene. A colorimetric change was used to report the results, which enables the outcome of viral RNA amplification to be read by the naked eye without the need of expensive or dedicated instrument. The sensitivity can be 80 copies of viral RNA per ml in a sample. We validated the RT-LAMP method in a hospital in China, employing 16 clinic samples with 8 positives and 8 negatives. The testing results are consistent with the conventional RT-qPCR. In addition, we also show that one-step process without RNA extraction is feasible to achieve RNA amplification directly from a sample. This rapid, simple and sensitive RT-LAMP method paves a way for a large screening at public domain and hospitals, particularly regional hospitals and medical centres in rural areas.
Background Physical activity is effective for the prevention and treatment of chronic disease, yet insufficient evidence is available to make comparisons regarding adherence to aerobic physical activity interventions among chronic disease populations, or across different settings. The purpose of this review is to investigate and provide a quantitative summary of adherence rates to the aerobic physical activity guidelines among people with chronic conditions, as physical activity is an effective form of treatment and prevention of chronic disease. Methods Randomized controlled (RCTs) trials where aerobic physical activity was the primary intervention were selected from PsychInfo, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Clinical Key, and SCOPUS from 2000 to 2018. Studies were included if the program prescription aligned with the 2008 aerobic physical activity guidelines, were at least 12 weeks in length, and included adult participants living with one of three chronic diseases. The data was extracted by hand and the PRISMA (preferred reporting items for systematic review and meta-analysis) guidelines were used to evaluate risk-of-bias and quality of evidence. Data were pooled using random-effect models. The primary outcome measure was program adherence and the secondary outcome measures were dropout and setting (e.g. home vs. clinic-based). Pooled effect sizes and 95% CiIs (confidence intervals) were calculated using random-effect models. Results The literature search identified 1616 potentially eligible studies, of which 30 studies (published between 2000 and 2018, including 3,721 participants) met the inclusion criteria. Three clinical populations were targeted: cancer ( n = 14), cardiovascular disease ( n = 7), and diabetes ( n = 9). Although not statistically significant, adherence rates varied across samples (65, 90, and 80%, respectively) whereas dropout rates were relatively low and consistent across samples (5, 4, and 3%). The average adherence rate, regardless of condition, is 77% (95% CI = 0.68, 0.84) of their prescribed physical activity treatment. The pooled adherence rates for clinic-based and home-based programs did not differ (74% [95% CI, 0.65, 0.82] and 80% [95% CI, 0.65, 0.91], respectively). Conclusions The current evidence suggests that people with chronic conditions are capable of sustaining aerobic physical activity for 3+ months, as a form of treatment. Moreover, home-based programs may be just as feasible as supervised, clinic-based physical activity programs.
Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma (DLBCL). However, the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determined. The core set of genes relating to histone methylation (KMT2D, KMT2C, EZH2), histone acetylation (CREBBP, EP300), DNA methylation (TET2), and chromatin remodeling (ARID1A) were detected in the training cohort of 316 patients by whole-genome/exome sequencing (WGS/WES) and in the validation cohort of 303 patients with newly diagnosed DLBCL by targeted sequencing. Their correlation with peripheral blood immune cells and clinical outcomes were assessed. Underlying mechanisms on tumor microenvironment were investigated both in vitro and in vivo. Among all 619 DLBCL patients, somatic mutations in KMT2D (19.5%) were most frequently observed, followed by mutations in ARID1A (8.7%), CREBBP (8.4%), KMT2C (8.2%), TET2 (7.8%), EP300 (6.8%), and EZH2 (2.9%). Among them, CREBBP/EP300 mutations were significantly associated with decreased peripheral blood absolute lymphocyte-to-monocyte ratios, as well as inferior progression-free and overall survival. In B-lymphoma cells, the mutation or knockdown of CREBBP or EP300 inhibited H3K27 acetylation, downregulated FBXW7 expression, activated the NOTCH pathway, and downstream CCL2/CSF1 expression, resulting in tumor-associated macrophage polarization to M2 phenotype and tumor cell proliferation. In B-lymphoma murine models, xenografted tumors bearing CREBBP/EP300 mutation presented lower H3K27 acetylation, higher M2 macrophage recruitment, and more rapid tumor growth than those with CREBBP/EP300 wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis. Our work thus contributed to the understanding of aberrant histone acetylation regulation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.
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