Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes.

PURPOSE: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)-positive breast cancer patients under different genotypes. MATERIALS AND METHODS: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. RESULTS: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). CONCLUSION: Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Oil-based drilling cuttings pyrolysis residues at a typical shale gas drilling field in Chongqing: pollution characteristics and environmental risk assessment.

With the rapid development of unconventional natural gas such as shale gas, many oil-based drilling cuttings and their pyrolysis residues are produced, which are defined as hazardous wastes. In this paper, the pollution status of petroleum hydrocarbons and the leaching toxicity of eight heavy metals (Pb, Cr, Zn, Mn, Cu, Cd, Ni, and Hg) in the pyrolysis residues were studied. The ecological risk and human health risk were evaluated in the scenario where pyrolytic residues were used for paving as building materials. The results showed that the content of petroleum hydrocarbons in the pyrolysis residues was 7643.16 ± 169.67 mg/kg. Zn in the pyrolysis residues was extremely polluted, Pb was moderately polluted, Cr, Cu, As were slightly polluted, and the leaching toxicity was far below the standard value. In the ecological risk assessment, the comprehensive potential ecological risk of multiple heavy metals in the pyrolysis residues was low. On the other hand, the pyrolysis residues had no non-carcinogenic risk to adults under the condition of paving, but there was an obvious non-carcinogenic risk to children, and the carcinogenic risk of adults and children was within an acceptable range. In addition, aiming at reducing the health risk of the population, suggestions were put forward to reduce the exposure risk of the population and the content of heavy metals in the pyrolysis residue, which provided a scientific reference for the standardized management of the pyrolysis residue of oil-based drilling cuttings and the research on the corresponding treatment process.

Soil microbial ecological effect of shale gas oil-based drilling cuttings pyrolysis residue used as soil covering material.

The residue derived from oil-based drilling cutting pyrolysis could be used as paving materials. Some petroleum hydrocarbons remain in the residue after pyrolysis and cause severe environmental pollution. In this study, the soil column leaching experiments were carried out under different leaching amounts, and the vertical migration characteristics of petroleum hydrocarbons in soil and the dynamic response mechanism of microorganisms to petroleum hydrocarbons were analyzed. The result showed that the soil pH value and water content with different leaching amounts did not differ significantly, but the vertical migration ability of each petroleum hydrocarbon component was different. In petroleum hydrocarbon contaminated soil, the relative abundance of Proteobacteria maintained a high level (23.6%-60.7%). At the genus level, the relative abundance of Massilia decreased with the leaching amount increased. According to PICRUSt, Monooxygenase [EC: 1.14.13.-] played a significant role in petroleum hydrocarbon degradation. While Long-chain-fatty-acid-CoA ligase [EC: 6.2.1.3] had the highest relative abundance. By studying the influence of shale gas oil-based drilling cuttings pyrolysis residue on soil physical and chemical properties and soil microorganisms, this work provides scientific ecological assessment for the resource application of pyrolysis residue.

The dominant microbial metabolic pathway of the petroleum hydrocarbons in the soil of shale gas field: Carbon fixation instead of CO2 emissions.

In shale gas mining areas, indigenous microorganisms degrade organic pollutants such as petroleum hydrocarbons into carbon dioxide (CO2) and water (H2O) through aerobic metabolism. A large quantity of CO2 emissions will exacerbate the "Greenhouse effect". Based on the clean sieved soil and oil-based drilling fluid in the shale gas mining area, this experiment set three concentration gradients (3523 ± 159 mg/kg, 8715 ± 820 mg/kg and 22,031 ± 1533 mg/kg) to treat the soil, and each group was disposed for the same amount of time (63 days). By analyzing the dynamic changes of microbial diversity and the abundance of key functional genes for carbon fixation, the impact of petroleum hydrocarbons on carbon fixation potential was discovered, and the natural attenuation law of petroleum hydrocarbons in contaminated soil was explored. It provided the scientific research basis of ecology for the carbon cycle, carbon allocation, and carbon fixation in microbial remediation of petroleum hydrocarbon contaminated soil. The results obtained indicated the following: i) The removal rate of petroleum hydrocarbons under high-concentration pollution (45.33 ± 3.90%) was significantly lower than low and medium-concentration pollution. The TPH concentration removal rate of each group was the largest in the early stage of culture (1-5d), and there was no significant correlation between the TPH content and the community composition (R2 = 0.0736, P > 0.05). ii) Composition and function of Carbon Fixation associated microbiota were assessed by 16S rRNA sequencing and PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states) analysis. The main carbon fixation pathway in this study is the reductive citric acid cycle, because there was no shortage of enzymes that can affect subsequent reactions.

Vasodilatory effect and structural-activity relationship of a group of iridoid glucosides from Phlomis likiangensis.

As a folk medicine, Phlomis likiangensis is traditionally used in China to activate collaterals and protect cardiovascular system. We hypothesized that the beneficial effects of Phlomis likiangensis may be related to vasodilatation. In the present study, twelve known iridoid glucosides (1-12) were isolated from Phlomis likiangensis. The vasodilatory effects and the underlying mechanisms of the main components (iridoid glucosides) of Phlomis likiangensis on rat aortic rings were investigated. The result showed that iridoid glucosides significantly increased the vasodilatation in rat aortic rings, which was abolished by removing the endothelium of the vessels or by eliminating the generation of nitric oxide. Finally, the structure-activity relationship of compounds 1-12 was also speculated. Our findings provide the first evidence that the iridoid glucosides of Phlomis likiangensis may be the pharmacodynamic basis for its traditional efficacy.