Investigation of the molecular mechanism of Danggui Buxue tang in treating lung cancer using network pharmacology and molecular docking techniques.

This study used network pharmacology and molecular docking techniques to investigate the molecular targets and pathways of Danggui Buxue Tang (DBT) in treating lung cancer. The compound-target network was constructed using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and a lung cancer-specific network was created using the GEO database and Cytoscape software. GO and KEGG pathway analyses were performed to understand the biological processes associated with DBT. The key compounds from Astragalus, kaempferol, and quercetin, and the potential targets are IL-6, IL-1ß, FOS, ICAM1, and CCL2. GO enrichment analysis revealed numerous biological process-related entries, while KEGG pathway analysis highlighted the TNF and IL-17 signalling pathways. Molecular docking confirmed the stable binding activity between the main active compounds of DBT and the target proteins. Overall, these findings shed light on the molecular mechanism of DBT in treating lung cancer, providing insights into targets, pathways, and biological processes involved.

Effects of Exogenous Application of Glycine Betaine Treatment on 'Huangguoggan' Fruit during Postharvest Storage.

Loss of quality in citrus fruit is a common occurrence during postharvest storage due to oxidative stress and energy consumption. In recent years, glycine betaine (GB) has been widely applied to postharvest horticulture fruit. This study aimed to investigate the effect of GB treatment (10 mM and 20 mM) on the quality and antioxidant activity of 'Huangguogan' fruit during postharvest storage at room temperature. Our results indicated that both 10 mM and 20 mM treatments effectively reduced weight and firmness losses and maintained total soluble solid (TSS), titratable acidity (TA), and ascorbic acid contents. Additionally, GB treatment significantly increased the activity of antioxidant enzymes, maintained higher levels of total phenols and total flavonoids, and led to slower accumulation of H2O2. A transcriptome analysis conducted at 28 days after treatment (DAT)identified 391 differentially expressed genes (DEGs) between 20 mM GB (GB-2) and the control (CK) group. These DEGs were enriched in various pathways, particularly related to oxygen oxidoreductase, peroxidase activity, and flavonoid biosynthesis. Overall, the application of GB proved beneficial in enhancing the storability and extending the shelf life of 'Huangguogan' fruit.

Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial.

PURPOSE: Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC. PATIENTS AND METHODS: This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients. RESULTS: Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months (P = .0570). The objective response rate was 4.6% v 2.7% (P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018). CONCLUSION: Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.

Prognostic analysis of Chinese patients with metastasis renal cell cancer receiving sorafenib: results from a multicenter long-term follow-up retrospective study.

The effects of sorafenib for Chinese patients with metastatic renal cell cancer (mRCC) were evaluated to figure out the relationship between clinical variables and prognosis. The data were analyzed retrospectively from six comprehensive cancer centers in Northeast China. All cases were diagnosed as mRCC histopathologically without exception. Patients were taken 400 mg sorafenib orally twice daily until progression of disease or intolerable toxic reaction occurred. Overall survival (OS), progression-free survival (PFS), and the influence of clinical variables on survival were appointed as main outcome measures. Clinical data were analyzed using SPSS statistical software. P<0.05 was considered as statistically significant. A total of 131 patients were available for survival analysis. The median follow-up periods were 16.9 months, and the median OS and PFS were 16.1 months and 10.5 months, respectively. Univariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), metastatic sites, and previous therapy were significantly associated with OS, whereas PFS was merely associated with ECOG PS and previous therapy. The multivariate analysis suggested that ECOG PS, metastatic sites, and previous therapy were the independent prognostic factors for OS, and ECOG PS and previous therapy as the independent prognostic factors for PFS. In the subgroup analysis for patients with visceral metastasis, the prognosis of patients with lung metastasis alone was better than those cases with liver metastasis alone or multiple organs metastasis. In our study, sorafenib shows a higher curative activity for patients with mRCC in Northeast China. ECOG PS, metastatic lesions, and previous therapy may be important parameters for OS and PFS prediction. Lung metastases alone may be a more sensitive indicator for sorafenib than other organ metastases.

[Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer].

OBJECTIVE: To investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer. METHODS: Forty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days. RESULTS: LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05). CONCLUSIONS: The use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.