Network pharmacology analysis and experimental validation of Xiao-Qing-Long-Tang's therapeutic effects against neutrophilic asthma.

BACKGROUND: Xiao-Qing-Long-Tang (XQLT), a classical Chinese herbal medicine formula, has been extensively used for allergic asthma treatment. However, there is limited research on its anti-inflammatory effects and mechanisms specifically in neutrophilic asthma (NA). PURPOSE: This study aims to investigate the potential therapeutic effects of XQLT against NA using a combination of network pharmacology and experimental validation. STUDY DESIGN: By utilizing traditional Chinese medicine and disease databases, we constructed an XQLT-asthma network to identify potential targets of XQLT for NA. In the experimental phase, we utilized an ovalbumin (OVA)/lipopolysaccharide (LPS)-induced model for neutrophilic asthma and examined the therapeutic effects of XQLT. RESULTS: Our research identified 174 bioactive components within XQLT and obtained 140 target genes of XQLT against asthma. Functional enrichment analysis revealed that these target genes were primarily associated with inflammation and cytokines. In the experimental validation, mice induced with OVA-LPS showcased eosinophilic and neutrophilic cell infiltration in peri-bronchial areas, elevated levels of IL-4 and IL-17 in both serum and lung, increased percentages of Th2 and Th17 cells in the spleen, as well as elevated levels of CD11b+ and CD103+ dendritic cells (DCs) within the lung. Treatment with XQLT effectively reduced IL-4 and IL-17 levels, decreased the percentages of Th2, Th17, CD11b+, and CD103+ DCs, and improved inflammatory cell infiltrations in lung tissues. These findings serve as a foundation for the potential clinical application of XQLT in neutrophilic asthma.

An improved prognostic model for predicting the mortality of critically ill patients: a retrospective cohort study.

A simple prognostic model is needed for ICU patients. This study aimed to construct a modified prognostic model using easy-to-use indexes for prediction of the 28-day mortality of critically ill patients. Clinical information of ICU patients included in the Medical Information Mart for Intensive Care III (MIMIC-III) database were collected. After identifying independent risk factors for 28-day mortality, an improved mortality prediction model (mionl-MEWS) was constructed with multivariate logistic regression. We evaluated the predictive performance of mionl-MEWS using area under the receiver operating characteristic curve (AUROC), internal validation and fivefold cross validation. A nomogram was used for rapid calculation of predicted risks. A total of 51,121 patients were included with 34,081 patients in the development cohort and 17,040 patients in the validation cohort (17,040 patients). Six predictors, including Modified Early Warning Score, neutrophil-to-lymphocyte ratio, lactate, international normalized ratio, osmolarity level and metastatic cancer were integrated to construct the mionl-MEWS model with AUROC of 0.717 and 0.908 for the development and validation cohorts respectively. The mionl-MEWS model showed good validation capacities with clinical utility. The developed mionl-MEWS model yielded good predictive value for prediction of 28-day mortality in critically ill patients for assisting decision-making in ICU patients.

Profiling of Tumor Microenvironment Components Identifies Five Stroma-Related Genes with Prognostic Implications in Colorectal Cancer.

Background: Tumor microenvironment (TME) significantly affects colorectal cancer (CRC) progression and therapeutic efficacy, particularly the infiltrating stromal components. This study profiled the TME composition of tumor tissue and identify TME-related, especially stroma-related genes having prognosis value in CRC patients. Materials and Methods: We used the ESTIMATE algorithm to assess stromal/immune component and divided 524 CRC cases of public dataset into high- and low-score groups. We analyzed the effect of the score on prognosis and extracted the differential expression genes (DEGs) between groups, which were stromal- and/or immune-related genes, and performed a prognostic investigation of the DEGs. Results: Higher stromal score correlated with poor survival, whereas the immune score was the inverse. By comparing global gene expression of cases with high vs. low stromal/immune scores, we extracted 474 stroma-related genes, 76 immune-related genes, and 498 intersection genes, which were explored by function enrichment and survival analysis. We identified the expression of five stroma-related genes (including ITGA7, PTPN14, SCG2, TNS1, and GRP) significantly associated with poorer survival, which were validated in the other two independent CRC cohorts. Conclusion: These results presented a comprehensive understanding of TME components and identified five stroma-related genes that predict poor outcomes in CRC patients.

Upregulation of SNHG14 suppresses cell proliferation and metastasis of colorectal cancer by targeting miR-92b-3p.

Ample evidence have demonstrated that long noncoding RNAs small nucleolus RNA host gene 14 (SNHG14) serves as a master regulator in various cancers. However, the exact mechanism of SNHG14 in colorectal cancer (CRC) remains unknown. In the present study, we concentrate on the potential function of SNHG14 in the pathogenesis of CRC. From the quantitative reverse transcription-polymerase chain reaction results, SNHG14 was found to be downregulated in CRC tissues compared with the normal mucous samples, and its low expression was significantly correlated with poor clinical outcomes. Overexpression of SNHG14 inhibited cell growth, induced cell apoptosis, suppressed migration and invasion by inhibiting epithelial-mesenchymal transition process. Furthermore, mechanistic studies revealed that miR-92b-3p could rescue the CRC progress induced by SNHG14. Consequently, SNHG14 exhibited low expression in CRC tissues and involved in CRC progression and metastasis by competing for miR-92b-3p, and SNHG14 could be used as a valuable biomarker and therapeutic target for CRC.

Serum YKL-40 positively correlates with MMP-9 and CRP in patients with acute ST segment elevation myocardial infarction following emergency treatment.

OBJECTIVE: To investigate the role of YKL-40 in ST segment elevation myocardial infarction (STEMI) and its relationship to C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9). METHODS: This prospective study included 358 STEMI patients who were sent to the Emergency Department of our hospital from April 2014 to December 2017. Serum levels of YKL-40, CRP and MMP-9 were determined using commercially available Enzyme linked immunosorbent assay (ELISA) kits. Major adverse cardiovascular events (MACE) and overall survival time were analyzed. RESULTS: GRACE scores (P < .001) and the levels of YKL-40 (P < .001), MMP-9 (P < .001), and CRP (P < .001) were significantly higher in deceased patients compared to those that survived. The levels of CRP (P = .007) and MMP-9 (P = .022) were significantly higher in the high YKL-40 group. The GRACE scores were also significantly elevated (P = .011, 95% CI 2.1 (-9.7 to -1.3)). Cumulative MACE rates and cardiac death rates were significantly higher in the high YKL-40 group (P < .001, 95% CI 3.9 (1.9-8.2)). Overall survival times were significantly longer in patients with lower YKL-40 levels (P < .0001). CONCLUSION: Elevated YKL-40 levels positively correlate with CRP and MMP-9 levels and are associated with clinical outcomes including MACE and 6-month survival in STEMI patients.

[Differentiation of transplanted mouse c-Kit+lin- bone marrow cells into hepatocytes in vitro].

OBJECTIVE: To ascertain whether mouse c-Kit(+)Lin- bone marrow cells have the potential of hepatic stem cells. METHODS: c-Kit(+)lin- bone marrow cells were isolated and purified by magnetic-activated cell sorting (MACS) from BALB/C male donor mice, and immediately transplanted into age-matched BALB/C syngeneic female mice with 35-Gy total liver irradiation. The recipients were sacrificed 1 month after the transplantation for pathological observation of the liver morphology. The presence of Y-chromosome was examined in the liver cells of the recipient by in situ hybridization (ISH), and alpha-fetoprotein (AFP) and albumin in the cells were detected by immunohistochemistry. RESULTS: The hepatocytes positive for Sry gene on Y-chromosome were identified 1 month after transplantation, and immunohistochemistry for AFP and albumin confirmed that the donor mice-derived cells were hepatocytes. CONCLUSION: c-Kit(+)lin- bone marrow cells have the potential of hepatic stem cells, which can reside and differentiate into hepatocytes in the liver after transplantation. c-Kit(+)lin- bone marrow cells can be used as the source cells of cell transplantation for liver disease.

[Analysis of factors for bacterial infection following liver transplantation].

OBJECTIVE: To investigate the association of surgical skills, anhepatic time and preoperative hepatic function grading with bacteria infection after the liver transplantation and identify the common bacterial flora involved for effective prevention and treatment of the posttransplant bacterial infection. METHODS;The clinical records of 31 cases of liver transplantation from August 2004 to August 2005 were reviewed and the collected data were analyzed statistically. RESULTS; Among the 31 cases, posttransplant bacterial infection occurred in 16 cases accounting for a total incidence of 51.61%, with the incidence of multi-system (or multi-organ) infection of 22.58%. The earlier cases had longer average surgery time and anhepatic period than the later cases, with also higher incidence of infection. Among the 19 patients with hepatic function class A before surgery, 7 acquired bacterial infection involving one system or organ, 2 had infections compromising multiple system or organ. In the 8 patients of hepatic function class B before surgery, 2 had single-system or -organ infection and 1 multi-system or -organ infection. Four out of the 5 patients with hepatic function class C before surgery acquired posttransplant bacterial infections, all involving multiple systems or organs. Pseudomonas aeruginosa was the most common bacteria responsible for the infections in these cases. CONCLUSION: Improvement of surgical skills can obviously reduce the incidence of bacterial infection after liver transplantation. No evidences suggest the correlation between the incidence of infections (including severe ones) and hepatic function class A or B before the operation, whereas patients with preoperative hepatic function class C seems to be at higher risk for infection involving multiple systems or organs. The anhepatic time does not significantly impact on the incidence or severity of the posttransplant infections, and Pseudomonas aeruginosa is the most common bacteria causing the infections.