Detection of MTAP Protein and Gene Expression in Non-small Cell Lung Cancer

Background and objective The abnormal expression of MTAP, a tumor suppressor gene, is found in a variety of tumor tissues. The aim of this study is to detect the expression of MTAP mRNA protein and the clinical significance for the therapy of non-small cell lung cancer tissue (NSCLC). Methods The expression of MTAP protein was detected by immunohistochemistry in 52 cases of NSCLC patients. The relative expression MTAP mRNA was detected by real-time quantitative PCR. Results The expression of MTAP protein in NSCLC tissue was significantly lower than that in paracarcinomous tissue and borderline lung tissue respectively (t=10.283, 10.940, P < 0.001). There was no significant difference among gender, age, smoking history, histology except differentiation (t=2.310, P=0.025). The MTAP mRNA relative expression in NSCLC tissue was significantly lower than that in paracarcinomous tissue (t=9.902, P < 0.001). Conclusion Downregulation of MTAP protein and gene expression is correlated to the oncogenesis and progression of NSCLC

Mineralogy and Geochemistry of Late Permian Coals within the Tongzi Coalfield in Guizhou Province, Southwest China

first_pagesettings Open AccessArticle Mineralogy and Geochemistry of Late Permian Coals within the Tongzi Coalfield in Guizhou Province, Southwest China by Baoqing Li 1,*,Xinguo Zhuang 1,Xavier Querol 1,2,Natalia Moreno 2OrcID,Linjian Yang 3,Yunfei Shangguan 1 andJing Li 1 1 Key Laboratory of Tectonics and Petroleum Resources (China University of Geosciences), Ministry of Education, Wuhan 430074, China 2 Institute of Environmental Assessment and Water Research, CSIC, C/Jordi Girona 18–26, 08034 Barcelona, Spain 3 No. 106 Geological Team of Guizhou Province Geology and Mineral Bureau, Zunyi 563000, China * Author to whom correspondence should be addressed. Minerals 2020, 10(1), 44; https://doi.org/10.3390/min10010044 Received: 18 December 2019 / Revised: 29 December 2019 / Accepted: 30 December 2019 / Published: 31 December 2019 (This article belongs to the Collection Minerals in Coal and Coal Combustion Products) Download PDF Browse Figures Abstract The lowermost Late Permian coal seam (C4 Coal) in the Tongzi Coalfield offers an opportunity to investigate the influence of terrigenous detrital materials from the Qianbei Upland on the mineralogical and geochemical patterns of the C4 Coal. The minerals are mainly dominated by pyrite and, to a lesser extent, tobelite, kaolinite, and calcite, along with traces of Al-oxyhydroxide minerals. The various degrees of marine influence may have resulted in the variation in the amount of Fe-sulfides (e.g., pyrite) and elements having Fe-sulfides affinity. Furthermore, the abundant Fe ions involved in the formation of Fe-sulfides were most likely derived from the claystone on the Qianbei Upland. The tobelite identified in the C4 Coal probably originated from the interaction between pre-existing kaolinite and NH4+ from NH3 released from the thermally affected organic matter at least shortly after the highly volatile bituminous stage under NH4+-rich and K+-poor conditions. The terrigenous detrital materials were derived from two possible sediment-region sources—the Qianbei Upland and Kangdian Upland—which is different from Late Permian coals in Western Guizhou Province. The claystone on the Qianbei Upland may have served as parent rock, as indicated by the presence of the Al-oxyhydroxide minerals as well as low SiO2/Al2O3 ratio (0.66 on average) and low quartz content. Meanwhile, the detrital materials from the Kangdian Upland most likely originated from the erosion of the felsic rocks at the uppermost part of the Kangdian Upland, as evidenced by the high Al2O3/TiO2 ratio (36.0 on average) and the strongly negative Eu anomaly (0.61 on average).The authors would like to give their sincere thanks to No. 106 Geological Team of Guizhou Province Geology for assistance during sampling and Institute of Environmental Assessment and Water Research, CSIC, Spain for assistance during the sample analysis. Also, many thanks are given to academic editor and two anonymous reviewers for their valuable comments on the manuscript.Peer reviewe

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole

Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis

Objective: This study aims to investigate the safety and efficacy of abrocitinib in treating moderate-to-severe AD in adolescents and adults.Methods: Pubmed, Cochrane, Embase, and Web of science data base were searched from inception to 9 August 2022. All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis.Results: This meta-analysis comprised 7 studies and found that 100 mg or 200 mg of abrocitinib significantly improved IGA {[RR = 2.44, 95% CI (1.93–3.08)] [RR = 3.16, 95% CI (2.52–3.96)]} and EASI-75{[RR = 2.18, 95%CI (1.78–2.67)] [RR = 3.04, 95%CI (2.22–4.16)]} responses compared to placebo. Following that, the population was divided into adolescent and adult groups. The abrocitinib improved IGA, EASI-75 responses, and it was still superior to placebo in both the adolescent and the adult groups. PP-NRS4 response index demonstrated that abrocitinib had a greater effect than placebo at 100 mg [RR = 2.22, 95% CI 1.80–2.72] and 200 mg [RR = 3.28, 95% CI 2.59–4.17]. Abrocitinib improved PSAAD, POEM, DLQI, CDLQI, and HADS more than a placebo.Conclusion: In conclusion, this meta-analysis preliminarily demonstrated that abrocitinib had higher efficacy and safety in the treatment of moderate-to-severe AD in adolescents and adults. In addition, abrocitinib could rapidly relieve itching, and effectively improve symptoms and signs, with a greater effect at the dosage of 200 mg than 100 mg

Clinical-dosimetric analysis of measures of dysphagia including gastrostomy-tube dependence among head and neck cancer patients treated definitively by intensity-modulated radiotherapy with concurrent chemotherapy

<p>Abstract</p> <p>Purpose</p> <p>To investigate the association between dose to various anatomical structures and dysphagia among patients with head and neck cancer treated by definitive intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy.</p> <p>Methods and materials</p> <p>Thirty-nine patients with squamous cancer of the head and neck were treated by definitive concurrent chemotherapy and IMRT to a median dose of 70 Gy (range, 68 to 72). In each patient, a gastrostomy tube (GT) was prophylacticly placed prior to starting treatment. Prolonged GT dependence was defined as exceeding the median GT duration of 192 days. Dysphagia was scored using standardized quality-of-life instruments. Dose-volume histogram (DVH) data incorporating the superior/middle pharyngeal constrictors (SMPC), inferior pharyngeal constrictor (IPC), cricoid pharyngeal inlet (CPI), and cervical esophagus (CE) were analyzed in relation to prolonged GT dependence, dysphagia, and weight loss.</p> <p>Results</p> <p>At 3 months and 6 months after treatment, 87% and 44% of patients, respectively, were GT dependent. Spearman's ρ analysis identified statistical correlations (p < 0.05) between prolonged GT dependence or high grade dysphagia with IPC V65, IPC V60, IPC Dmean, and CPI Dmax. Logistic regression model showed that IPC V65 > 30%, IPC V60 > 60%, IPC Dmean > 60 Gy, and CPI Dmax > 62 Gy predicted for greater than 50% probability of prolonged GT dependence.</p> <p>Conclusion</p> <p>Our analysis suggests that adhering to the following parameters may decrease the risk of prolonged GT dependence and dysphagia: IPC V65 < 15%, IPC V60 < 40%, IPC Dmean < 55 Gy, and CPI Dmax < 60 Gy.</p