Explicating the property and action of traditional Chinese medicine (TCM) in the perspectives of modern science deepens the insight into the property of TCM, and provides the basis for new drug discovery and clinical therapy. In this study, we investigated the relationship between transient receptor potential melastatin 8 (TRPM8) and pungent flavor using three-dimensional pharmacophores based on virtual screening methods. Firstly, an inhouse database was established to identify the related pharmacological action according to the traditional Chinese herbs expressing an action of promoting blood circulation. Then, several therapeutic targets, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), cholesteryl ester transfer protein (CETP), Niemann-Pick C1-Like 1 (NPC1L1) and platelet-activating factor receptor (PAFR), were selected to screen traditional Chinese herbs, and the common virtual screening hits with various hit scores providing data to reveal the correlation among TRPM8 and therapeutic targets. According to the screening results, TRPM8 agonists were able to identify the effective components of pungent herbs and TRPM8, which shares the common virtual screening hits with the therapeutic targets, was considered to be related to the action of pungent taste. The novel ideas and methods in this study are beneficial to unveil the scientific relationship between a TCM property and its action.
Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in the process of renal ischemia-reperfusion (IR) injury and myocardial IR injury. However, its mechanism in liver IR injury is not clear. IR and hypoxia/reoxygenation (H/R) model were built on C57BL/6 mice. Blood samples were obtained from the inferior vena cava of the model mice. MALAT1 expression was detected in IR model and H/R model. Supported by experimental results, the impacts of MALAT1 on viability, apoptosis, and inflammation of H/R model cells were detected. The correlation between MALAT1 and downstream genes was analyzed by mechanism assays. MALAT1 was detected to be upregulated in IR model and H/R model. MALAT1 knockdown had inhibitory effects on apoptosis and inflammatory reaction while promoting liver cell viability in H/R condition. Meanwhile, MALAT1 targeted miR-150-5p to regulate antizyme inhibitor 1 (AZIN1) in liver cells. Finally, MALAT1 regulated viability, apoptosis, and inflammatory reaction of liver cells by targeting miR-150-5p and AZIN1. To conclude, MALAT1 targeted miR-150-5p/AZIN1 to accelerate liver IR injury, suggesting that MALAT1 might be a novel target for liver IR injury.
Objective
To investigate the prognostic value of PSI, APACHEⅡ and SOFA scores in patients with hospital-acquired pneumonia and the effect of age on the efficacy of SOFA score.
Methods
The data of 80 patients with hospital-acquired pneumonia admitted in our hospital from January 2016 to December 2017 were retrospectively analyzed. Among them, 40 had non-perioperative hospital-acquired pneumonia and 40 had perioperative hospital-acquired pneumonia. Each group was evaluated by the PSI, APACHEⅡand SOFA scores with the worst physiological parameters within 24 hours after confirmed diagnosis of hospital-acquired pneumonia. Using the survival rate after 30 days as a prognostic index, the operating characteristic curves (ROCs) of the receivers were drawn to compare the difference of the three scores. On the basis of APACHEⅡ age scores, SOFA scores were re-graded to compare the effect of SOFA scores before and after age-weighting.
Results
ROC analysis showed that the three scores could predict the 30-day mortality of hospital-acquired pneumonia. For the 40 cases of non-perioperative hospital-acquired pneumonia, the areas under the curve (AUCs) of ROC in PSI, APACHEⅡ and SOFA were 0.75, 0.69 and 0.66, respectively. And for the 40 cases of perioperative hospital-acquired pneumonia, the AUCs in PSI, APACHEⅡ and SOFA were 0.87, 0.64 and 0.70, respectively. And for the 80 cases of hospital-acquired pneumonia, the AUCs in PSI, APACHEⅡ and SOFA were 0.80, 0.73 and 0.66, respectively. After age-weighting of the SOFA scores, the AUC of the 40 cases of non-perioperative hospital-acquired pneumonia was 0.75, the AUC of the 40 cases of perioperative hospital-acquired pneumonia was 0.75, and the AUC of the 80 cases of hospital-acquired pneumonia was 0.72.
Conclusion
The efficacy of PSI is better than that of APACHEⅡ and SOFA regardless of whether the patient is in surgery, and the efficacy of SOFA score is increased after age-weighting.
Key words:
PSI; APACHEⅡ; SOFA; Hospital-acquired pneumonia
Abstract Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy. Here we performed a comprehensive proteogenomic analysis of 198 samples from Chinese AMPAC patients and duodenum patients. Genomic data illustrate that 4q loss causes fatty acid accumulation and cell proliferation. Proteomic analysis has revealed three distinct clusters (C-FAM, C-AD, C-CC), among which the most aggressive cluster, C-AD, is associated with the poorest prognosis and is characterized by focal adhesion. Immune clustering identifies three immune clusters and reveals that immune cluster M1 (macrophage infiltration cluster) and M3 (DC cell infiltration cluster), which exhibit a higher immune score compared to cluster M2 (CD4 + T-cell infiltration cluster), are associated with a poor prognosis due to the potential secretion of IL-6 by tumor cells and its consequential influence. This study provides a comprehensive proteogenomic analysis for seeking for better understanding and potential treatment of AMPAC.