Genome-wide analysis of genomic signatures might reveal novel mechanisms for gastric cancer (GC) tumorigenesis. Here, we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as
CCND1, ERBB2
and
MYC
. Specifically, we nominate a novel hotspot involving the super-enhancer of
ZFP36L2
presents in approximately 10% GCs from different cohorts, the oncogenic role of which is further confirmed by experimental data. In addition, our data reveal a mutational signature, specifically occurring in noncoding region, significantly enriched in tumors with
cadherin 1
mutations, and associated with poor prognoses. Collectively, our data suggest that TDs might serve as an important mechanism for cancer gene activation and provide a novel signature for stratification.
BackgroundChinese herbal medicine (CHM) has been used in China and some other countries for the treatment of patients with functional dyspepsia (FD). However, controlled studies supporting the efficacy of such treatments in patients with FD are lacking. In this trial, we aimed to assess the efficacy and safety of modified LiuJunZi decoction in patients with FD of spleen-deficiency and qi-stagnation syndrome.MethodsWe performed a randomized, double-blind, placebo-controlled trial with patients from five centers. Patients with FD of spleen-deficiency and qi-stagnation syndrome (n = 160) were randomly assigned to groups given CHM modified LiuJunZi decoction or placebo in a 2:1 ratio. Herbal or placebo granules were dissolved in 300 ml of boiled water cooled to 70°C. Patients in both groups were administered 150 ml (50°C) twice daily. The trial included a 4-week treatment period and a 4-week follow-up period. The primary outcomes were dyspepsia symptom scores, measured by the total dyspepsia symptom scale and the single dyspepsia symptom scale at weeks 0, 1, 2, 3, 4 and 8. The secondary outcome was the change of radiopaque barium markers emptied from the stomach between week 0 and week 4 of treatment.ResultsCompared with patients in the placebo group, patients in the CHM group showed significant improvements according to the scores of total dyspepsia symptoms and single dyspepsia symptoms obtained from patients (P < 0.01) and investigators (P < 0.01). They also showed an improvement in the number of radiopaque barium markers emptied from the stomach (P < 0.05).ConclusionsCHM modified LiuJunZi decoction appears to offer symptomatic improvement in patients with FD of spleen-deficiency and qi-stagnation syndrome.Trial registrationChinese Clinical Trial Registry (ChiCTR): http://ChiCTR-TRC-10001074
Mango (Mangifera indica) is widely grown across southern China, especially in the provinces of Guangxi, Hainan, Yunnan, Sichuan, and Taiwan. Guangxi itself has over 86,667 ha of mango production. The purpose of this study was to identify Colletotrichum species associated with mango in different parts of Guangxi and examine their pathogenicity on leaves and fruits of mango in vitro. Diseased leaves were collected from 25 mango orchards in different areas of Guangxi province. Sixty-five isolates were obtained from mango leaves with anthracnose symptoms, and these were further characterized based on morphology and DNA sequencing. Twenty-nine isolates from different areas were selected for sequencing and analyses of the internal transcribed spacer region, glyceraldehyde-3-phosphate dehydrogenase, partial actin, β-tubulin, and chitin synthase genomic regions. The most common fungal isolates were these three species: Colletotrichum asianum, C. fructicola, and C. siamense. C. asianum was the most common and widely distributed in Guangxi (51.7%), followed by C. fructicola (37.9%) and C. siamense (10.2%), both found in Tiandong, Tianyang, and Wuming counties. There was no evidence of geographical specialization of the different species. Pathogenicity assays showed that all isolates were pathogenic to mango leaves and fruit (cultivar Tainong). No relationship was found between origin of isolates and their virulence. This is the first description of C. asianum, C. fructicola, and C. siamense as causal agents of mango leaf anthracnose from Guangxi province, China.
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