Stress is an important contributing factor in the outbreak of infectious fish diseases. To comprehensively understand the impact of catecholamine stress hormone norepinephrine (NE) on the pathogenicity of Aeromonas hydrophila, we assessed variations in bacterial growth, virulence-related genes expression and virulence factors activity after NE addition in serum-SAPI medium. Further, we assessed the effects of NE on A. hydrophila virulence in vivo by challenging fish with pathogenic strain AH196 and following with or without NE injection. The NE-associated stimulation of A. hydrophila strain growth was not linear-dose-dependent, and only 100 μM, or higher concentrations, could stimulate growth. Real-time PCR analyses revealed that NE notably changed 13 out of the 16 virulence-associated genes (e.g. ompW, ahp, aha, ela, ahyR, ompA, and fur) expression, which were all significantly upregulated in A. hydrophila AH196 (p < 0.01). NE could enhance the protease activity, but not affect the lipase activity, hemolysis, and motility. Further, the mortality of crucian carp challenged with A. hydrophila AH196 was significantly higher in the group treated with NE (p < 0.01). Collectively, our results showed that NE enhanced the growth and virulence of pathogenic bacterium A. hydrophila.
Background Real world evidence is important for informing healthcare practice and developing medical products and has gained broad interest in healthcare. Compound Kushen Injection (CKI) has been widely applied into treatment of colon carcinoma (CC) in China. Postapproval drug assessment related retrospective studies using electrical medical record (EMR) collected from hospital information system (HIS) is one of the most important categories of real-world study (RWS). Based on HIS EMR, interrelationships of combined medication of CKI in treating CC can be validated in real world settings. Methods This study was conducted based on a large-scale integrated database of EMR derived from HIS. EMR of 3328 patients initially diagnosed with CC among 49,597 patients treated with CKI were included in the study. Descriptive statistical analyses and apriori algorithm based association rule analyses were performed, respectively, to validate frequency distribution and interrelationships of combined medication of CKI in treating CC. Results The pharmacological mechanisms of TCMs that have been commonly used in conjunction with CKI include heat-clearing and detoxifying, qi-reinforcing, blood circulation-promoting and stasis-removing, blood-stanching, and qi-regulating. For modern medicines, antibiotics, antineoplastic chemotherapeutic drugs, immunomodulator, 5-HT receptor antagonist drugs, and corticosteroids are most often combined with CKI. The association rules of medication combinations of CKI in treating CC in real world manifest certain laws for both TCMs and modern medicines. They are generally in line with CC treatment guidelines. Conclusions It is a common practice for CKI to be integrated with both modern medicines and TCMs when treating CC in China. The associations of medication combinations of CKI in treating CC manifest certain laws for both TCMs and modern medicines. The RWS for validating interrelationships of combined medication may provide evidence for rational use of CKI. Further explorations are needed to verify and expand the conclusions.
IntroductionThe transition from chronic non-atrophic gastritis (CNAG) to chronic atrophic gastritis (CAG) and gastric carcinoma (GC) is regarded as a representative disease model of gastric mucosa malignant transformation led by uncontrolled inflammation. Traditional Chinese medicine (TCM) syndrome-targeted therapies have been applied in treating chronic gastritis (CG) malignant transformation in China with satisfying efficacy. This study aims to validate TCM syndrome features in each stage of CG malignant transformation. The findings may shed light on the TCM hypothesis of CG malignant transformation, and thus optimise syndrome-targeted treatment strategies of CNAG, CAG and GC, respectively.Methods and analysisThe present study is a cross-sectional study conducted in China. A total of 2000 eligible patients, including 500 CNAG cases, 1000 CAG cases and 500 GC cases, will be recruited from four TCM hospitals. Primary outcome measures include the prevalence of TCM syndrome patterns in varied stages of CG malignant transformation. Secondary outcome measures include prevalence and severity of all the presenting signs and symptoms collected by using TCM four diagnostic methods. Descriptive analysis, comparative analysis and correlation analysis of all the measurement data will be performed by biostatisticians. Unsupervised data mining analyses, including exploratory factor analysis, association rule analysis, hierarchical clustering analysis, complex system entropy clustering analysis, and so on, will also be performed by data scientists respectively for in-depth analyses of TCM syndrome-related indicators.Ethics and disseminationThe protocol has been approved by the Ethical Review Board of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine (No ECPJ-BDY-2014-02). All the study outcomes will be disseminated through national conference reports and in the meantime published on peer-reviewed journals.Trial registration numberNCT03314038; Pre-results.
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