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1.
Environ Int ; 137: 105527, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32007690

RESUMO

BACKGROUND: Previous studies have observed that cadmium (Cd) exposure of pregnant women was associated with increased risk of gestational diabetes mellitus (GDM). However, the potential mechanism still remains unclear. In addition, various animal studies have suggested that Cd exposure could affect fatty acids (FAs) metabolism, but data on humans are scant. OBJECTIVES: We conducted a nested case-control study to investigate the associations of urinary Cd concentrations with levels of circulating FAs and risk of GDM in pregnant women, and further to examine the role of FAs in mediating the relationship between Cd exposure and risk of GDM. METHODS: A total of 305 GDM cases were matched to 305 controls on pregnant women's age (±2 years) and infant's gender from a birth cohort study conducted in Wuhan, China. Urinary Cd concentrations and levels of plasma FAs between 10 and 16 gestational weeks were measured using inductively coupled plasma mass spectrometry and gas chromatography-mass spectrometry, respectively. Conditional logistic regressions models were used to estimate the associations of Cd concentrations and levels of FAs with the risk of GDM. Multiple linear regression models were applied to estimate the associations between Cd concentrations and levels of FAs. Mediation analysis was used to assess the mediating role of FAs in the association of Cd with the risk of GDM. RESULTS: Urinary concentrations of Cd in cases (median: 0.69 µg/L) were significantly higher than controls (median: 0.59 µg/L, P < 0.05). Cd concentrations were positively associated with the risk of GDM (Ptrend = 0.003). Compared to the first tertile of Cd, the adjusted odds ratios (95% confidence intervals) of GDM risk were 2.08 (1.29, 3.36) for the second tertile and 2.09 (1.32, 3.33) for the third tertile. Cd concentrations were positively correlated with levels of eicosadienoic acid and arachidonic acid/eicosapentaenoic acid ratio, but negatively correlated with levels of stearic acid, eicosapentaenoic acid, total odd-chain saturated fatty acids, total n-3 polyunsaturated fatty acids (PUFAs), and n-3 PUFAs/n-6 PUFAs ratio. We did not observe evidence that the association of Cd exposure and risk of GDM was mediated through FAs. CONCLUSIONS: Our findings confirmed the association of higher Cd exposure with increased risk of GDM in pregnant women, and provided forceful epidemiological evidence for the relation of Cd concentrations and levels of FAs.

3.
Am J Clin Nutr ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31974579

RESUMO

BACKGROUND: Whether genetic susceptibility to type 2 diabetes is modified by a healthy lifestyle among Chinese remains unknown. OBJECTIVES: The aim of the study was to determine whether genetic risk and adherence to a healthy lifestyle contribute independently to the risk of developing type 2 diabetes. METHODS: We defined a lifestyle score using BMI, alcohol intake, smoking, physical activities, and diets in 461,030 participants from the China Kadoorie Biobank and 38,434 participants from the Singapore Chinese Health Study. A genetic risk score was constructed based on type 2 diabetes loci among 100,175 and 16,172 participants in each cohort, respectively. A Cox proportional-hazards model was used to estimate the interaction between genetic and lifestyle factors on the risk of type 2 diabetes. RESULTS: In 2 independent Asian cohorts, we consistently found a healthy lifestyle (the bottom quintile of lifestyle score) was associated with a substantially lower risk of type 2 diabetes than an unhealthy lifestyle (the top quintile of lifestyle score) regardless of genetic risk. In those at a high genetic risk, the risk of type 2 diabetes was 57% lower among participants with a healthy lifestyle than among those with an unhealthy lifestyle in the pooled cohorts. Among participants at high genetic risk, the standardized 10-y incidence of type 2 diabetes was 7.11% in those with an unhealthy lifestyle vs. 2.45% in those with a healthy lifestyle. CONCLUSIONS: In 2 independent cohorts involving 558,302 Chinese participants, we did not observe an interaction between genetics and lifestyle with type 2 diabetes risk, but our findings provide replicable evidence to show lifestyle factors and genetic factors were independently associated with the risk of type 2 diabetes. Within any genetic risk category, a healthy lifestyle was associated with a significantly lower risk of type 2 diabetes among the Chinese population.

4.
Eur J Med Chem ; 188: 112012, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31911293

RESUMO

Starting from a bipyridine-sulfonamide scaffold, medicinal chemistry optimization leads to the discovery of a novel Plasmodium falciparum PI4K kinase (PfPI4K) inhibitor compound 15g (CHMFL-PI4K-127, IC50: 0.9 nM), which exhibits potent activity against 3D7 Plasmodium falciparum (P. falciparum) (EC50: 25.1 nM). CHMFL-PI4K-127 displays high selectivity against PfPI4K over human lipid and protein kinase. In addition, it exhibits EC50 values of 23-47 nM against a panel of the drug-resistant strains of P. falciparum. In vivo, the inhibitor demonstrates the favorable pharmacokinetic properties in both rats and mice. Furthermore, oral administration of CHMFL-PI4K-127 exhibits the antimalaria efficacy in both blood stage (80 mg/kg) and liver stage (1 mg/kg) of Plasmodium in infected rodent model. The results suggest that CHMFL-PI4K-127 might be a new potential drug candidate for malaria.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31957946

RESUMO

Lead halide perovskites with mixed cations/anions often suffer from phase segregation, which is detrimental to device efficiency and their long-term stability. During perovskite film growth, the gel stage (in between liquid and crystalline) correlates to phase segregation, which has been rarely explored. Herein, cation diffusion kinetics are systematically investigated at the gel stage to develop a diffusion model obeying Fick's second law. Taking 2D layered perovskite as an example, theoretical and experimental results reveal the impact of diffusion coefficient, temperature, and gel duration on the film growth and phase formation. A homogenous 2D perovskite thin film was then fabricated without significant phase segregation. This in-depth understanding of gel stage and relevant cation diffusion kinetics would further guide the design and processing of halide perovskites with mixed composition to meet requirements for optoelectronic applications.

6.
J Hazard Mater ; 386: 121663, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31784133

RESUMO

Exposure to polycyclic aromatic hydrocarbons and phthalates are linked to lung function decline and altered relative telomere length (RTL) accompanying with oxidative stress and inflammatory events in human body. However, limited data are available about impacts of co-exposure of PAHs and phthalates on lung function and RTL. We conducted a pilot study with repeated measures during the winter of 2014 and summer of 2015 in Wuhan city, China. Participants took part in the measures of lung function, RTL, urinary monohydroxylated-PAHs (OH-PAHs) and phthalate metabolites over three consecutive days in each season. Linear mixed-effect (LME) models and Bayesian kernel machine regression (BKMR) were used to analyze the relations of OH-PAHs or phthalate metabolites with lung function or RTL. LME models showed the negative associations of 3-day average of hydroxyphenanthrene (2 + 3-, 4-OHPhe) or 1-hydroxypyrene with FEV1, 3-day average of 2 + 3-OHPhe with FVC. BKMR models revealed the negative relation of eight OH-PAHs with FEV1, FVC or RTL; nine phthalate metabolites may counteract an overall effect of eight OH-PAHs on FEV1, FVC or RTL. The findings indicated that urinary phthalate metabolites may counteract the negative association of urinary OH-PAHs on FEV1 or FVC, which may be partially linked to shorter RTL regarding biological aging.

7.
J Hazard Mater ; 385: 121618, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31791866

RESUMO

With increasing shortage of clean water, rainwater has been considered as a precious alternative drinking water source. The processes applied to rainwater treatment are responsible for the safety of drinking water. Therefore, we systematically compared different disinfection processes to evaluate the control of disinfection by-product (DBP) formation and integrated cyto- and genotoxicity of the treated rainwater for the first time. The evaluated disinfection processes included chlorination and chloramination, pre-oxidation by potassium permanganate (KMnO4) and potassium ferrate (K2FeO4), ultraviolet/hydrogen peroxide (UV/H2O2), and ultraviolet/persulfate (UV/PS) processes. The results revealed that chloramination was effective for controlling the formation of carbonaceous DBPs (C-DBPs), but not nitrogenous DBPs (N-DBPs). Compared to KMnO4 pre-oxidation, better reduction of almost all DBPs was observed during K2FeO4 pre-oxidation. According to the calculation of cytotoxicity index (CTI) and genotoxicity index (GTI), cyto- and genotoxicity of the samples decreased obviously at the dosage of ≥ 2.0 mg/L KMnO4 and K2FeO4. The control of the cyto- and genotoxicity of the formed DBPs from the two UV-related AOPs was more effective at the dosage of ≥ 1.0 mM PS and ≥ 5.0 mM H2O2. Moreover, UV/PS was much more powerful to alter the structure of DBP precursors in rainwater.

8.
Cell Stem Cell ; 26(1): 17-26.e6, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31761724

RESUMO

Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment.

9.
J Comput Biol ; 27(1): 55-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31424286

RESUMO

Adamantinomatous craniopharyngioma (ACP) is a congenital epithelial tumor in the sellar region with benign histological manifestation but invasive. Currently, surgery is the main treatment for it, but its recurrence rate is high. Therefore, it is of great importance to explore the mechanism of occurrence and development of ACP and to identify new molecules. One gene expression profile, GSE94349, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis was used to make enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we performed the construction and analysis of the protein-protein interaction (PPI) network and significant module. The analysis of the GSE94349 dataset identified 109 DEGs, consisting of 80 upregulated genes and 29 downregulated genes in ACP samples compared with normal brain tissues. Functional and pathway enrichment analysis of DEGs provided a comprehensive overview of some major pathophysiological mechanisms in ACP: RNA polymerase II promoter, glutamate receptor binding, and so on. A total of 10 hub genes of DEGs were obtained from the PPI network, which provided potential therapeutic targets for the ACP. In summary, there were DEGs between ACP tissues and normal brain tissues, which may be involved in the mechanisms of occurrence and development of ACP, especially via the regulation of RNA polymerase II promoter and glutamate receptor binding. Key genes in DEGs could serve as new research targets for the diagnosis and treatment of ACP.

10.
Int Urol Nephrol ; 52(1): 187-196, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31828476

RESUMO

BACKGROUND: Cisplatin could result in a wide range of kidney injuries. During the pathogenetic process, the excessive generation of reactive oxygen species (ROS) induced by cisplatin has been regarded as the initial and critical role, by which DNA damage and cell death could subsequently come up. Therefore the elimination of ROS has long been considered as effective mean to prevent cisplatin-induced kidney injury. Myricitrin is a newfound natural polyphenol hydroxy flavonoid glycoside compound, whose forceful anti-oxidative properties had been confirmed. Thus, we aim to investigate if myricitrin could protect against cisplatin-induced kidney injury. METHODS: A cisplatin-induced kidney injury model was established in mice by intraperitoneal injection of cisplatin. The protective effect of myricitrin on kidney injury was evaluated by serum BUN and Cre level. The Kidney pathology was observed with H&E and TUNEL staining. Then cell viability and apoptosis rate were measured using MMT assay and flow cytometry to assess if myricitrin could protect KH-2 cells against cisplatin-induced injury. The intracellular ROS was detected by ROS fluorogenic probe and quantitatively analyzed by flow cytometry. Finally, the expression of Bcl-2 and Bax was investigated by western blotting to indicate the influence in apoptosis pathway. RESULTS: Myricitrin could significantly remit kidney injury induced by cisplatin and inhibit apoptosis of KH-2 cells. In mechanism, myricitrin could eliminate ROS and subsequently block activation of apoptosis pathway. CONCLUSION: Myricitrin protects against cisplatin-induced kidney injury by eliminating excessive ROS.

11.
Sci Total Environ ; 702: 134942, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710848

RESUMO

This study compared the degradation of dissolved organic matter (DOM) by UV/chlorine advanced oxidation processes (AOPs) with emerging ultraviolet light-emitting diode (UV-LED, 275 nm) and traditional low pressure UV (LPUV, 254 nm) as UV sources. Excitation emission matrix-parallel factor (EEM-PARAFAC) analysis and two-dimensional (2D) correlation gel permeation chromatograph were applied to explore the evolutions of DOM during oxidation processes. The degradation behaviors of DOM indicated by UV absorbance at 254 nm (UV254), dissolved organic carbon (DOC), and fluorophores fitted the pseudo-first-order kinetics well. The removal efficiency of DOM was similar under UV-LED and LPUV irradiation alone. However, UV-LED exhibited much higher degradation rates (increased by 29-160%) than LPUV regardless of the tracking variables during UV/chlorine processes. For three PARAFAC components, humic-like fluorescences were preferentially degraded by UV/chlorine oxidation compared with protein-like fluorescence potentially due to the differences of electronic moieties and molecular weight (MW). The decline in UV254, DOC, and fluorophores increased with increasing chlorine dosage; linear correlations between those indicators were observed during the two AOPs. Moreover, UV-LED/chlorine could achieve greater extents of MW change. Our study demonstrated that UV-LED could be a superior alternative for the future selection of UV source in the UV/chlorine process.

12.
Chemosphere ; 240: 124761, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31546190

RESUMO

The formation and control of haloacetamides (HAcAms) in drinking water have raised high attention due to their high genotoxicity and cytotoxicity, especially the most cytotoxic one, diiodoacetamide (DIAcAm). In this study, the degradation of DIAcAm by UV/chlorination was investigated in terms of degradation kinetics, efficiency, influencing factors, oxidation products and toxicity evaluation. Results revealed that the degradation of DIAcAm by UV/chlorine process followed pseudo-first-order kinetics, and the rate constant between DIAcAm and OH radicals was determined as 2.8 × 109 M-1 s-1. The contribution of Cl to DIAcAm degradation by UV/chlorine oxidation was negligible. Increasing chlorine dosage and decreasing pH significantly promoted the DIAcAm degradation during UV/chlorine oxidation, but the presence of bicarbonate (HCO3-) and natural organic matter (NOM) inhibited it. The mass balance analysis of iodine species was also evaluated during UV/chlorine oxidation of DIAcAm. In this process, with DIAcAm decreasing from 16.0 to 0.8 µM-I in 20 min, IO3-, I- and HOI/I2 increased from 0 to 6.3, 6.1 and 0.5 µM-I, respectively. The increase of CHO cell viability during DIAcAm degradation indicated that the toxicity of DIAcAm could be decreased by chlorination, UV irradiation and UV/chlorine oxidation treatments, in which UV/chlorine oxidation was more effective on toxicity reduction than chlorination and UV irradiation alone.


Assuntos
Acetamidas/química , Poluentes Químicos da Água/química , Cloro/análise , Halogenação , Cinética , Oxirredução , Raios Ultravioleta , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Purificação da Água/métodos
13.
J Biomed Mater Res A ; 108(1): 127-135, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31515867

RESUMO

The foreign body reaction (FBR) is described as a local chronic inflammation after implantation of biomaterials in which macrophages involved intimately. At the stage of acute inflammation, mast cells release histamine, Interleukin-4 (IL-4) and Interleukin-13 (IL-13), enhancing recruitment, and fusion of macrophages in the following phase. As for chronic intensive inflammation, degradation of biomaterials would be promoted by macrophage-derived foreign body giant cells releasing degradative enzymes, acid and reactive oxygen intermediates. Nevertheless, it could be seen as a breakthrough point for regulating FBR, considering the dominant role of the macrophage in the immune response as exemplified by the decrease of IL-4 and IL-13, stabilizing an appropriate balance between two macrophage phenotypes, selectively suppressing some function of macrophages, and so on. Moreover, the relationship between macrophages polarization and the development of a fibrous capsule, which increase the possibility of implantation failure, will be illustrated later. This review aims at providing readers a comprehensive understanding of FBR and its correlative treatment strategy.

14.
Sci Total Environ ; 702: 135056, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31731128

RESUMO

Limited researches are available on seasonal variation of inhalation exposure of polycyclic aromatic hydrocarbons (PAHs) and its cancer risk assessment in China. We recruited 20 fresh postgraduates and measured outdoor and indoor (dormitories, offices and laboratories) daily PM2.5 concentrations in four seasons (seven consecutive days in every season) during 2014 -2015, calculated daily potential doses of personal exposure to total Benzo[a]pyrene equivalent concentration (BaPeq) in the microenvironments based on the total BaPeq and the time-activity patterns, and estimated incremental lifetime cancer risk (ILCR) using Monte Carlo method. Daily average concentrations of PM2.5-bound ∑PAHs on the campus ranked from high to low were winter, autumn, spring, summer in the dormitories and offices. Daily average concentration of PM2.5-bound ∑PAHs were higher in indoor environments than outdoor in the same season, except for that of PM2.5-bound ∑PAHs in laboratories in the winter. Median values of ILCR in both sexes from high to low were winter (men vs. women: 5.35e-9 vs. 4.96e-9), spring (3.71e-9 vs. 4.00e-9), autumn (2.92e-9 vs. 3.02e-9), summer (1.71e-9 vs. 1.87e-9). Indoor and outdoor PM2.5-bound PAHs concentrations showed seasonal and spatial variations. The ILCR value for PM2.5-bound PAHs was higher in women than in men.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Exposição por Inalação/estatística & dados numéricos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Adulto , China/epidemiologia , Humanos , Neoplasias/epidemiologia , Medição de Risco , Estações do Ano
15.
J Eval Clin Pract ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31849153

RESUMO

RATIONALE, AIMS, AND OBJECTIVES: Failure mode and effects analysis (FMEA) is a valuable reliability management tool that can preemptively identify the potential failures of a system and assess their causes and effects, thereby preventing them from occurring. The use of FMEA in the healthcare setting has become increasingly popular over the last decade, being applied to a multitude of different areas. The objective of this study is to review comprehensively the literature regarding the application of FMEA for healthcare risk analysis. METHODS: An extensive search was carried out in the scholarly databases of Scopus and PubMed, and we only chose the academic articles which used the FMEA technique to solve healthcare risk analysis problems. Furthermore, a bibliometric analysis was performed based on the number of citations, publication year, appeared journals, authors, and country of origin. RESULTS: A total of 158 journal papers published over the period of 1998 to 2018 were extracted and reviewed. These publications were classified into four categories (ie, healthcare process, hospital management, hospital informatization, and medical equipment and production) according to the healthcare issues to be solved, and analyzed regarding the application fields and the utilized FMEA methods. CONCLUSION: FMEA has high practicality for healthcare quality improvement and error reduction and has been prevalently employed to improve healthcare processes in hospitals. This research supports academics and practitioners in effectively adopting the FMEA tool to proactively reduce healthcare risks and increase patient safety, and provides an insight into its state-of-the-art.

16.
JAMA Netw Open ; 2(12): e1918070, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31851351

RESUMO

Importance: Treatment of locally advanced non-small cell lung cancer (NSCLC) remains challenging. The rationale of combining a cyclooxygenase 2 (COX-2) inhibitor with concurrent chemoradiation (CCRT) was based on results of preclinical research and prospective clinical studies; however, no randomized clinical trial has provided evidence of a direct comparison with CCRT alone. Objective: To determine the effect of combined selective COX-2 inhibition with standard CCRT on survival among patients with unresectable stage III NSCLC. Design, Setting, and Participants: A single-center, open-label, randomized phase 2 clinical trial was performed among 96 patients who had histologically and cytologically confirmed unresectable stage III NSCLC. Participants were enrolled from November 2011 to August 2015. Data were analyzed from February to October 2018. Intervention: Patients were randomized to receive thoracic radiation, 60 Gy, for 6 weeks concurrent with etoposide and cisplatin or the same regimen of CCRT combined with 200 mg of celecoxib, taken twice daily. Main Outcomes and Measures: The primary end point was overall survival. The secondary end points were the proportion of patients with treatment-related toxic effects, progression-free survival, and overall survival in subgroups with and without the COX-2 genotype. Results: A total of 100 patients were randomized. Following the exclusion of 4 outliers, 96 participants (96.0%) were analyzed (51 randomized to CCRT alone and 45 randomized to CCRT with celecoxib; mean [SD] age, 60.0 [8.3] years; 73.0 [76.0%] male). The median overall survival time was 32.8 (95% CI, 17.0-48.5) months in the group that received CCRT with celecoxib and 35.5 (95% CI, 25.8-45.2) months in the group that received CCRT alone (P = .88). Celecoxib with CCRT was well tolerated; the incidence of symptomatic radiation pneumonitis was 6.6% (95% CI, 1.4%-18.0%) in the group that received CCRT with celecoxib and 11.8% (95% CI, 4.4%-23.9%) in the group that received CCRT alone (P = .49). Among patients with the high-risk genotype, celecoxib plus CCRT was not associated with higher progression-free survival (hazard ratio, 0.36; 95% CI, 0.13-1.04; P = .05) or overall survival (hazard ratio, 0.50; 95% CI, 0.15-1.72; P = .26) compared with CCRT alone. Conclusions and Relevance: In unresectable stage III NSCLC, adding celecoxib to concurrent chemoradiation did not improve survival. A smaller, not statistically significant proportion of patients in the CCRT with celecoxib group compared with the CCRT alone group developed symptomatic radiation pneumonitis. Among patients with the high-risk genotype, adding celecoxib to CCRT did not improve overall or progression-free survival. Trial Registration: ClinicalTrials.gov identifier: NCT01503385.

17.
Invest New Drugs ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31872348

RESUMO

Acute myeloid leukemia (AML) is reported to be vulnerable to transcription disruption due to transcriptional addiction. Cyclin-dependent kinase 9 (CDK9), which regulates transcriptional elongation, has attracted extensive attention as a drug target. Although several inhibitors, such as alvocidib and dinaciclib, have shown potent therapeutic effects in clinical trials on AML, the lack of high selectivity for CDK9 and other CDKs has limited their optimal clinical efficacy. Therefore, developing highly selective CDK9 inhibitors is still imperative for the efficacy and safety profile in treating AML. Here, we report a novel highly selective CDK9 inhibitor, JSH-009, which exhibited high potency against CDK9 and displayed great selectivity over 468 kinases/mutants. It also demonstrates impressive in vitro and in vivo antileukemic efficacy in preclinical models of AML, which makes JSH-009 a useful pharmacological tool for elucidating CDK9-mediated transcription and a novel therapeutic candidate for AML.

18.
J Clin Oncol ; : JCO1901162, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841363

RESUMO

PURPOSE: RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non-small-cell lung cancer (NSCLC). METHODS: The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS). RESULTS: Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively (P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months (P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% (P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms. CONCLUSION: A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.

20.
Adv Healthc Mater ; 8(24): e1901301, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31763779

RESUMO

Due to their excellent size, designability, and outstanding targeted antibacterial effects, nanoparticles have become a potential option for controlling oral biofilm-related infections. However, the formation of an oral biofilm is a dynamic process, and factors affecting the performance of antibiofilm treatments are complex. As such, when examining the existing literature on the antibiofilm effects of nanoparticles, attention should be paid to the specific mechanisms of action at different stages of oral biofilm formation, as well as relevant influencing factors, in order to achieve an objective and comprehensive evaluation. This review is intended to detail the antibacterial mechanisms of nanoparticles during the four stages of the formation of oral biofilms: 1) acquired film formation; 2) bacterial adhesion; 3) early biofilm development; and 4) biofilm maturation. In addition, factors influencing the antibiofilm properties of nanoparticles are summarized from the aspects of nanoparticles themselves, biofilm models, and host factors. The limitations of current research and possible trends for future research are also discussed. In summary, nanoparticles are a promising antioral biofilm strategy. It is hoped that this review can serve as a reference and inspire ideas for further research on the application of nanoparticles for effectively targeting and treating oral biofilms.

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