Discussion on the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation technology.

To explore the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation. The active ingredients and potential targets were screened by the Systematic Pharmacological Analysis Platform of Traditional Chinese Medicine (TCMSP). Hypertension-related targets were obtained from OMIM and GeneCards databases. Common targets between drug and hypertension were screened in the Venny platform. A protein-protein interaction (PPI) network was constructed in the STRING database using intersection targets. Key targets in PPI network were analyzed by Cytoscape. R language program was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding abilities of the main active ingredients to critical targets were verified by molecular simulation. Naringenin, quercetin, kaempferol, and ß-sitosterol in Lingguizhugan Decoction, and potential targets such as STAT3, AKT1, TNF, IL6, JUN, PTGS2, MMP9, CASP3, TP53, and MAPK3, were screened out. KEGG Enrichment analysis revealed that the common targets of Lingguizhugan Decoction and hypertension are mainly involved in the lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and IL17 signaling pathway. The molecular simulation results showed that naringenin-MAPK3, quercetin-MMP9, quercetin-PTGS2, and quercetin-TP53 were the top four in the docking scores. Naringenin-MAPK3 and quercetin-MMP9 were stable, with binding free energies of -27.97 ± 1.41 kcal/mol and -21.15 ± 3.17 kcal/mol, respectively. The possible mechanism of Lingguizhugan Decoction in treating hypertension is characterized of multi-component, multi-target, and multi-pathway.Communicated by Ramaswamy H. Sarma.

A Clinical Study on Microwave Ablation in Combination with Chemotherapy in Treating Peripheral IIIB-IV Non-Small Cell Lung Cancer.

Background: This study investigated the efficacy and complications of microwave ablation in combination with chemotherapy in treating peripheral IIIB-IV non-small cell lung cancer (NSCLC). Materials and Methods: A total of 100 patients with peripheral IIIB-IV NSCLC were randomly divided into two groups: combination group (n = 52) and chemotherapy group (n = 48). Patients in the combination group were treated with microwave ablation, radiotherapy, and chemotherapy, whereas the patients in the chemotherapy group were treated with pemetrexed disodium or gemcitabine hydrochloride, cisplatin chemotherapy, and conventional radiotherapy. Results: The effectiveness and disease control rates were significantly higher in the combination group than in the chemotherapy group (p < 0.05). The second- and third-year survival rates were significantly higher in the combination group than in the chemotherapy group (p < 0.05). However, patients in the combination group had no serious complications, and there were no intraoperative and perioperative deaths. Conclusions: Microwave ablation is safe and effective. Combination chemotherapy is superior to chemotherapy in treating peripheral IIIB-IV NSCLC in terms of effectiveness rate, disease control rate, and extended patient survival time.

Effect of Pseudomonas aeruginosa on the expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the airway of bronchiectasis patients.

OBJECTIVE: To study the expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the airway of bronchiectasis (BE) patients, and evaluate the effect of pseudomonas aeruginosa (PAE) on the expression of TIMP-1 and MMP-9. METHODS: In this case-control study, subjects were divided into BE group and control group, and the BE group was further divided into PAE group and other bacteria group based on the culture results of bronchoalveolar lavage fluid (BALF). BALF was obtained by bronchoscopy, the expressions of MMP-9 and TIMP-1 were determined by ELISA, then the ratio of TIMP-1/MMP-9 was calculated. Furthermore, the tissue of bronchic endomembrane was obtained by transbronchial biopsy and the expressions of MMP-9 and TIMP-1 were determined using immunohistochemical method. RESULTS: The levels of MMP-9 in the BALF of PAE group and other bacteria group were significantly higher than that in control group (P=0.0000 both), and the expressions of MMP-9 in bronchic endomembrane of PAE group and other bacteria group were also significantly higher (P=0.0421 and 0.0003, respectively). The level of TIMP-1 in BALF of PAE group was significantly lower than that in other bacteria group (P=0.0324). The ratio of TIMP-1/MMP-9 in BALF of BE group was significantly lower than that in control group(P=0.0000), and this ratio of PAE group was significantly lower than those in both other bacteria group and control group (P=0.0026 and 0.0000, respectively). CONCLUSION: PAE infection in BE patients can suppress the expression of TIMP-1 and stimulate the expression of MMP-9, and thus make the disease even worse.