Integrating network pharmacology and experimental verification to explore the mechanism of puerarin against oliguria in acute alcoholism.

Purpose: This study was designed to evaluate the pharmacological mechanisms of puerarin against oliguria in acute alcoholism via network pharmacology analysis combined with experimental verification. Methods: First, this study established an acute alcoholism rat model, compared the changes in urine volume in each group, and observed the therapeutic effect of puerarin by H&E staining, biochemical, RT-qPCR, and immunohistochemical analyses. Second, puerarin-related targets were searched in TCMS, PubChem, CNKI, Wanfang, PubMed, and GeenMedical Academic databases. Also, potential disease targets were obtained from the GeneCards, MalaCards, and NCBI-gene databases and genes with puerarin target gene intersections were screened out. The interaction network for co-predicted targets was obtained using the STRING database, and the core targets were imported into Cytoscape for visualization using DAVID Bioinformatics Resources 6.8. The essential genes were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses to predict related biological processes and significant signaling pathways. Finally, molecular docking was used to examine the interaction of puerarin with key targets, and the core targets were validated further by RT-qPCR and Western blotting. Results: Compared to the model group, the urine volume of the rats was significantly increased after puerarin treatment, and the levels of anti-diuretic hormone (ADH) and aquaporin 2 (AQP2) expression were decreased. Searching the intersection of puerarin and acute alcoholism targets yielded 214 potential targets, 837 biological processes, and 185 signaling pathways involved. The molecular docking results indicated a good affinity between puerarin and key targets (cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding protein (CREB), and c-Fos). RT-qPCR and Western blotting further verified that puerarin could down-regulate the expression of cAMP/PKA/CREB/c-Fos. Conclusion: This study identified the potential targets of puerarin against oliguria in rats with acute alcoholism using network pharmacology and animal experiments. The mechanism may be closely related to the cAMP signaling pathway.

[Source Analysis and Composition Characteristics of Water-soluble Ions During Spring Festival in Ningbo].

Water-soluble ions and some trace gases during the Spring Festival in Ningbo were observed using an ion online gas composition and aerosol monitoring system. Combined with meteorological elements data, the source analysis and composition characteristics of water-soluble ions and trace gases were analyzed. The average concentration of ρ(PM2.5) during the observation period was 33.1 µg·m-3, and there was light pollution. The order of concentration of water-soluble ions was NO3->SO42->NH4+>K+>Cl->Na+>Ca2+>Mg2+. The secondary inorganic ions ρ(NO3-), ρ(SO42-), and ρ(NH4+) were the most water-soluble ions, which were 12.5, 10.5, and 7.2 µg·m-3, respectively. According to the PMF source analysis, firecracker combustion, secondary generation (background, industrial source), and dust sources were the major sources of fine particles during the observation period, and their contribution rates of PM2.5 were 21.9%, 64.5%, and 13.6%, respectively. When the secondary generation was the main pollution, NH4+ accounted for 92.2% of the cations. When firecracker combustion was the main pollution from New Year's Eve to the second day, the proportion of K+ions significantly increased. Dust sources were affected by regional transport from the northwest direction. When the dust source was the main pollution, the proportion of K++Ca2+and Na++Mg2+ increased.

Detection of Gegen Adulteration Using Multiple Fingerprints Coupled With Chemometric Strategy.

BACKGROUND: The root of Pueraria montana var. lobata (gegen) is a well-known traditional Chinese medical herb, which is prone to be accidentally contaminated with Pueraria montana var. thomsonii, Pueraria wallichii, and Pueraria peduncularis due to the morphological character similarity. These adulterations might cause quality confusion and safety issues. OBJECTIVE: In this study, the screening technique to detect adulteration in gegen was developed using multiple fingerprints and chemometrics. METHOD: A range of gegen samples and possible known adulterants including Pueraria montana var. thomsonii, Pueraria wallichii, and Pueraria peduncularis were collected. FT-IR and HPLC coupled with different chemometric techniques, including similarity analysis (SA), hierarchical clustering analysis (HCA), principal component analysis (PCA), and orthogonal partial least-squares discriminant analysis (OPLS-DA), provide the qualitative chemometric models for gegen adulteration detection. RESULTS: FT-IR and HPLC combined with OPLS-DA successfully differentiated authentic gegen from adulterants. Both FT-IR and HPLC units can be used as alternative methods to traditional methods. The HPLC showed better performance in identifying samples than FT-IR. CONCLUSIONS: The use of FT-IR and HPLC coupled with chemometrics could potentially be the proper selection method for the early quality evaluation of gegen. This method can be used to combat fraud in the herbal industry in the future. HIGHLIGHTS: FT-IR and HPLC combined with chemometrics analysis were developed to discriminate between Pueraria lobata (gegen) and adulterants. The multiple fingerprints combined with multivariate methods were successfully applied to the study of the gegen and its adulterants. The chemometrics analysis using SA and OPLS-DA indicate significant differentiation in the chemical composition of these species. This research provides important chemotaxonomic references in species identification.

A Dynamic Nomogram for 3-Month Prognosis for Acute Ischemic Stroke Patients After Endovascular Therapy: A Pooled Analysis in Southern China.

Cerebral edema (CDE) is a common complication in patients with acute ischemic stroke (AIS) and can reduce the benefit of endovascular therapy (EVT). To determine whether certain risk factors are associated with a poor prognosis mediated by CDE after EVT. The 759 patients with anterior circulation stroke treated by EVT at three comprehensive stroke centers in China from January 2014 to October 2020 were analyzed. Patients underwent follow-up for 3 months after inclusion. The primary endpoint was a measure of a poor prognosis (modified Rankin Scale score ≥ 3) at 3 months assessed in all patients receiving EVT. Least absolute shrinkage and selection operator and multivariate logistic regression were used to select variables for the prognostic nomogram. Based on these variables, the nomogram was established and validated. In addition, structural equation modeling was used to explore the pathways linking CDE and a poor prognosis. Seven predictors were identified, namely, diabetes, age, baseline Alberta Stroke Program Early CT score, modified Thrombolysis in Cerebral Infarction score, early angiogenic CDE, National Institutes of Health Stroke Scale score, and collateral circulation. The nomogram consisting of these variables showed the best performance, with a large area under the curve in both the internal validation set (0.850; sensitivity, 0.737; specificity, 0.887) and external validation set (0.875; sensitivity, 0.752; specificity, 0.878). In addition, CDE (total path coefficient = 0.24, P < 0.001) served as a significant moderator. A nomogram for predicting a poor prognosis after EVT in AIS patients was established and validated with CDE as a moderator.

[Plasma homocysteine levels in ischemic stroke patients with obstructive sleep apnea].

OBJECTIVE: To investigate the association of plasma homocysteine and OSA (obstructive sleep apnea) syndrome in ischemic stroke (IS). METHODS: A total of 92 male IS patients were classified by apnea hypopnea index (AHI) into 2 groups: non-OSA group (AHI < 5/h) and OSA group (AHI > or = 5). All patients were tested for plasma homocysteine when polysomnography was finished at (14 +/- 2) d after the onset of IS. RESULTS: The mean level of homocysteine was significantly higher in the OSA group than that in the non-OSA group (17 +/- 5 vs 11 +/- 3 micromol/L, P < 0.01). Pearson correlation analysis revealed a positive correlation between the homocysteine level and the severity of AHI (r = 0.482, P < 0.01). Further multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine level (R2 = 0.553, P < 0.01, beta for AHI = 0.671, beta for folate = -0.256). CONCLUSION: The severity of OSA is significantly associated with an elevated level of homocysteine in IS patients. And this association is independent of other causative factors of an elevated level of homocysteine.

[A comparative study on early toxicity of conditioning regimen with or without antithymocyte globulin].

OBJECTIVE: To evaluate the toxicity of conditioning regimens of modified Bu/Cy +/- antithymocyte (ATG) in early stage after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A hundred patients with hematological malignancies undergoing allo-HSCT were assessed. Forty-two patients (group A) were conditioned with modified Bu/Cy regimen, 58 (group B) with modified Bu/Cy+ATG regimen. The occurrence of toxicity during the early stage after transplantation was evaluated and compared, including non-infectious fever, diarrhea, hepatotoxicity, mucositis and hematological toxicity. RESULTS: In group A and B, the incidence of non-infectious fever was 4.8% vs 81.0%, transaminase elevation 59.5% vs 65.5%, bilirubin elevation 16.7% vs 48.3%, diarrhea 59.5% vs 79.3% and mucositis 45.2% vs 37.9%, respectively, white blood cells reached zero occurred at a median of +3 d and -3 d, the rate of red cell and platelet transfusion-dependence, within 10 days before transplantation was 11.9% vs 32.8 and 16.7% vs 82.8%, respectively. CONCLUSIONS: Significant higher incidence of non-infectious fever, diarrhea, hepatotoxicity, leukopenia, and transfusion dependence is found and considered to be related to the administration of ATG in the conditioning regimen.