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ObjectiveTo detect the genotoxicity of Coreopsis tinctoria Nutt.（water extract） and provide research data for its safety evaluation.MethodsThe water extract of Coreopsis tinctoria Nutt. was used as the test substance in bacterial reverse mutation test， mouse lymphoma Assay （MLA） with and without metabolic activation S9； and the powder of Coreopsis tinctoria Nutt. was used in micronucleus test. Ames test based on the plate incorporation method was performed to detect his-/trp- revert mutation capabilities of S．typhimurium TA98， TA100， TA1535， TA1537 and E．coli WP2 uvrA induced under four doses of 1.25， 2.5， 5 and 10 mg/ plate； MLA based on the microporous method was performed to detect the increase of tk-+/- mutation frequency （MF） of L5178Y cells induced by 5 concentrations of 1.5， 2.0， 2.5， 3.0 and 3.5 mg/mL under the treatment condition of ±S9/3 h， and to evaluate the damage effects on the tested cells； for the mouse bone marrow micronucleus test： CD-1 mice were administrated with 900 mg/kg， 1 800 mg/kg and 3 600 mg/kg of the Coreopsis tinctoria Nutt. powder （200 mesh） intragastrically for three times at an interval of 24 h， and the samples were collected by 18-24 h after the last dose. The micronucleated cells in 2 000 polychromatic erythrocytes were counted， and the micronucleated cell rate were calculated.ResultsUnder both conditions absent and present S9， the numbers of the revertants in five strains induced by 1.25~10 mg/dish （equivalent to crude drug： 8.33~66.67 mg/plate） were not significantly increased compared with the negative （solvent） control of sterilized water for injection. The MF induced by 1.5~3.5 mg/mL （equivalent to crude drug： 10~23.33 mg/mL） were significantly increased with a concentration-response relationship， and most of the mutants were in the form of small colony. The T-MF and S-MF induced by 3.0 and 3.5 mg/mL +S9 groups were more than 3 times of the negative control group： the mean micronucleus rates in 900 mg/kg， 1 800 mg/kg and 3 600 mg/kg groups were 0.85±0.58， 1.10±0.97 and 1.45±1.12， respectively， with no significant difference compared with the deionized water negative control group.ConclusionThe water extract of Coreopsis tinctoria Nutt. could significantly increase the mutation frequency of tk+/- gene and led to chromosome damage in L5178Y cells， no matter with or without metabolic activation， suggesting its potential genotoxicity to human.

BackgroundVentricular septal rupture (VSR) is a type of cardiac rupture, usually complicated by acute myocardial infarction (AMI), with a high mortality rate and often poor prognosis. The aim of our study was to investigate the factors influencing the long-term prognosis of patients with VSR from different aspects, comparing the evaluation performance of the Gensini score, Sequential Organ Failure Assessment (SOFA) score and European Heart Surgery Risk Assessment System II (EuroSCORE II) score systems.MethodsThis study retrospectively enrolled 188 patients with VSR between Dec 9, 2011 and Nov 21, 2021at the First Affiliated Hospital of Zhengzhou University. All patients were followed up until Jan 27, 2022 for clinical data, angiographic characteristics, echocardiogram outcomes, intraoperative, postoperative characteristics and major adverse cardiac events (MACEs) (30-day mortality, cardiac readmission). Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality.ResultsThe median age of 188 VSR patients was 66.2 ± 9.1 years and 97 (51.6%) were males, and there were 103 (54.8%) patients in the medication group, 34 (18.1%) patients in the percutaneous transcatheter closure (TCC) group, and 51 (27.1%) patients in the surgical repair group. The average follow-up time was 857.4 days. The long-term mortality of the medically managed group, the percutaneous TCC group, and the surgical repair group was 94.2, 32.4, and 35.3%, respectively. Whether combined with cardiogenic shock (OR 0.023, 95% CI 0.001–0.054, P = 0.019), NT-pro BNP level (OR 0.027, 95% CI 0.002–0.34, P = 0.005), EuroSCORE II (OR 0.530, 95% CI 0.305–0.918, P = 0.024) and therapy group (OR 3.518, 95% CI 1.079–11.463, P = 0.037) were independently associated with long-term mortality in patients with VSR, and this seems to be independent of the therapy group. The mortality rate of surgical repair after 2 weeks of VSR was much lower than within 2 weeks (P = 0.025). The cut-off point of EuroSCORE II was determined to be 14, and there were statistically significant differences between the EuroSCORE II < 14 group and EuroSCORE II≥14 group (HR = 0.2596, 95%CI: 0.1800–0.3744, Logrank P < 0.001).ConclusionPatients with AMI combined with VSR have a poor prognosis if not treated surgically, surgical repair after 2 weeks of VSR is a better time. In addition, EuroSCORE II can be used as a scoring system to assess the prognosis of patients with VSR.

Background Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)–mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR -mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. Methods Inclusion criteria were biopsy-proven EGFR -mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. Results A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P  < .001), and the median OS was 17.4 months vs 25.5 months (P  < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. Conclusions As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR -mutated NSCLC. [ABSTRACT FROM AUTHOR]

The present study aimed to identify potential anticancer effects of Cucurbitacin I regulators on cell growth of human non-small cell lung cancer (NSCLC) and to explore their mechanism. The results indicated that the anticancer effects of Cucurbitacin I markedly attenuated cell proliferation, and induced apoptosis in NSCLC. Furthermore, Cucurbitacin I suppressed phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), phosphorylation (p)-AKT and p-p70S6K pathway in NSCLC. Then, (PI3K) inhibitor increased anticancer effects of Cucurbitacin I on NSCLC. In conclusion, the present results indicated that Cucurbitacin I inhibited cell growth of human NSCLC through PI3K/AKT/p70S6K signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual., Methods: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided., Results: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial., Conclusions: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC., (© The Author(s) 2022. Published by Oxford University Press.)