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Pharmaceutical Chemistry Journal - Cyclin-dependent kinases 4 and 6 (CDK4/6) are the core part of the cell cycle control machinery, which bind to cyclin D to regulate cell G1-S cycle conversion....  相似文献   
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Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.  相似文献   
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Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.  相似文献   
25.
Odontology - To investigate the characterization and function of a novel porous osteogenic material (PLLA / DDM) containing polylactic acid and demineralized dentin matrix. The surface morphology...  相似文献   
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Patient navigation is a strategy for overcoming barriers to reduce disparities and to improve access and outcomes. The aim of this umbrella review was to identify, critically appraise, synthesize, and present the best available evidence to inform policy and planning regarding patient navigation across the cancer continuum. Systematic reviews examining navigation in cancer care were identified in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Cumulative Index of Nursing and Allied Health (CINAHL), Epistemonikos, and Prospective Register of Systematic Reviews (PROSPERO) databases and in the gray literature from January 1, 2012, to April 19, 2022. Data were screened, extracted, and appraised independently by two authors. The JBI Critical Appraisal Checklist for Systematic Review and Research Syntheses was used for quality appraisal. Emerging literature up to May 25, 2022, was also explored to capture primary research published beyond the coverage of included systematic reviews. Of the 2062 unique records identified, 61 systematic reviews were included. Fifty-four reviews were quantitative or mixed-methods reviews, reporting on the effectiveness of cancer patient navigation, including 12 reviews reporting costs or cost-effectiveness outcomes. Seven qualitative reviews explored navigation needs, barriers, and experiences. In addition, 53 primary studies published since 2021 were included. Patient navigation is effective in improving participation in cancer screening and reducing the time from screening to diagnosis and from diagnosis to treatment initiation. Emerging evidence suggests that patient navigation improves quality of life and patient satisfaction with care in the survivorship phase and reduces hospital readmission in the active treatment and survivorship care phases. Palliative care data were extremely limited. Economic evaluations from the United States suggest the potential cost-effectiveness of navigation in screening programs.  相似文献   
27.
In this paper we present a coupled Finite Element Method – Boundary Element Method (FEM-BEM) approach for the solution of the free-boundary axi-symmetric plasma equilibrium problem. The proposed method, obtained from an improvement of the Hagenow-Lackner coupling method, allows to efficiently model the equilibrium problem in unbounded domains by discretizing only the plasma region; the external conductors can be modelled either as 2D or 3D models, according to the problem of interest. The paper explores different iterative methods for the solution of the nonlinear Grad-Shafranov equation, such as Picard, Newton-Raphson and Newton-Krylov, in order to provide a robust and reliable tool, able to handle large-scale problems (e.g. high resolution equilibria). This method has been implemented in the FRIDA code (FRee-boundary Integro-Differential Axisimmetric – https://github. om/matteobonotto/ FRIDA), together with a suitable Adaptive Integration Technique (AIT) for the computation of the source term. FRIDA has been successfully tested and validated against experimental data from RFX-mod device, and numerical equilibria of an ITER-like device.  相似文献   
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癫痫发作后状态(PIS)是指癫痫发作停止到恢复至发病前水平的异常状态,包括认知、运动、感觉、自主神经和精神行为等异常,症状多样,严重程度不一,持续数秒至数天不等,对患者的健康和生活质量产生很大影响。然而,目前国内外相关的研究较少,临床医生对此缺乏正确认识,容易误诊误治。本文将从PIS的定义、病理生理机制、临床表现、诊断和鉴别诊断、临床意义以及干预策略等进行综述,以提高临床医生的认识,并为今后临床研究提供参考。  相似文献   
30.
孙莉  赵毅 《现代肿瘤医学》2019,(13):2420-2424
三阴性乳腺癌(triple negative breast cancer,TNBC)是雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)及人类表皮生长因子受体(human epidermal growth factor-2,HER-2)均不表达的乳腺癌。按其功能特征可归纳为5类分子分型:以DNA修复缺陷或生长因子为途径的基底细胞样三阴性乳腺癌;以上皮-间充质转化和肿瘤干细胞为特征的间质样三阴性乳腺癌;免疫调节型三阴性乳腺癌;雄激素受体过表达的管腔/分泌型三阴性乳腺癌;HER-2富集型三阴性乳腺癌。三阴性乳腺癌恶性程度高且异型性较大,其治疗困难且预后较差,内分泌治疗及靶向治疗不敏感。目前很多学者对于三阴性乳腺癌的治疗各有研究,并有临床试验证实下述治疗有效。  相似文献   
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