24 research outputs found
Plasminogen Alleles Influence Susceptibility to Invasive Aspergillosis
Invasive aspergillosis (IA) is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855) correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser) where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn) was also identified in the human homolog (PLG; Gene ID 5340). An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT) recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection
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Transcriptomic analyses identify key differentially expressed genes and clinical outcomes between triple-negative and non-triple-negative breast cancer
There are significant differences in the biological behavior between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC). In the present study, we identify key differential genes and clinical outcomes between TNBC and non-TNBC.
Transcriptomic analyses used GEO datasets (GSE76275), gene ontology, KEGG pathway analysis and cBioPortal. Quantitative RT-PCR analysis (qRT-PCR) was used to validate the differentially expressed genes. We used the KM Plotter Online Tool and 240 patients with TNBC tissue microarray to assay the prognostic value of
.
The upregulated differentially expressed genes were enriched in transcription factor activity, sequence-specific DNA binding and nucleic acid binding transcription factor activity. Only 16 genes were upregulated when further screened for fold change >4-fold change.
and
exhibited high frequencies of change of greater than 10% (
was close to 20%). qRT-PCR results indicated that
and
mRNA levels were significantly upregulated in TNBC samples. In KM Plotter Online Tool, high
was associated with worse outcome. In our tissue microarray (including 240 TNBC tissues), IHC analysis revealed that 29.7% (55/240) of the tumor samples exhibited high
expression and 70.3% (185/240) of the tumor samples exhibited low
expression levels. Meanwhile, high
group has a bad prognosis.
The status of transcriptional activation is an important difference between TNBC and non-TNBC.
is a key differential gene associated with poor outcome in TNBC. Epigenetic therapy and agents targeting cancer/testis antigens might potentially help to customize therapies of TNBC
Efficacy of quadruple therapy with clarithromycin based on faecal molecular antimicrobial susceptibility tests as first-line treatment for Helicobacter pylori infection: a protocol of a single-centre, single-blind, randomised clinical trial in China
Introduction Helicobacter pylori is the most well-known risk factor for gastric cancer. Antibiotic resistance is the main reason for the failure of H. pylori eradication, and understanding the antibiotic resistance before treatment may be the main determinant of successful eradication of H. pylori. This study aims to evaluate the efficacy and safety of quadruple therapy based on faecal molecular antimicrobial susceptibility tests for the first-line eradication of H. pylori infection.Methods and analysis This is a single-centre, single-blind, randomised controlled trial, enrolling 855 patients with H. pylori infection. Patients are randomised to three groups for a 14-day treatment: group A: amoxicillin- and clarithromycin-based bismuth-containing quadruple therapy (BQT) (rabeprazole 10 mg, amoxicillin 1 g, clarithromycin 500 mg and colloidal bismuth 200 mg two times per day); group B: clarithromycin medication history-based BQT (rabeprazole 10 mg, amoxicillin 1 g, furazolidone 100 mg (with clarithromycin medication history)/clarithromycin 500 mg (without clarithromycin medication history) and colloidal bismuth 200 mg two times per day); group C: antimicrobial susceptibility test-based BQT (rabeprazole 10 mg, amoxicillin 1 g, clarithromycin 500 mg (clarithromycin-sensitive)/furazolidone 100 mg (clarithromycin resistant) and colloidal bismuth 200 mg two times per day). The primary end point is the eradication rate. The secondary end points are the incidence of adverse events and compliance.Ethics and dissemination This study was approved by the Ethics Committee of Second Affiliated Hospital, School of Medicine, Zhejiang University (Number 20230103). The results will be published in the appropriate peer-reviewed journal.Trial registration number NCT05718609