Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced ...Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.展开更多
To advance the knowledge of the environmental fate of sulfamethoxazole （SMX）, we systematically investigated the effects of natural water constituents and synthetic substances （i.e., TiO2 nanoparticles （nTiO2） an...To advance the knowledge of the environmental fate of sulfamethoxazole （SMX）, we systematically investigated the effects of natural water constituents and synthetic substances （i.e., TiO2 nanoparticles （nTiO2） and Ti-doped ^-Bi203 （NTB）） on the photodegradation kinetics of SMX under xenon lamp irradiation. The photolysis of SMX in aqueous solution followed first-order kinetics. Our results showed that higher concentrations of SMX, fulvic acid, suspended sediments, NTB and higher pH value decreased the photodegradation rates of SMX, whereas H202 improved the SMX photodegradation. TiO2 nanoparticles had a dual effect on pbotodegradation due to their photocatalytic activity and photoabsorption of photons. No intermediates more toxic toward Vibrio fischeri than SMX were produced after direct photolysis and photocatalytic degradation for 3 hr. The photolysis of SMX involved three pathways： hydroxylation, cleavage of the sulfonamide bond, and fragmentation of the isoxazole ring. This study lays the groundwork for a better understanding of the environmental fate of SMX.展开更多
Domestic coal stove is widely used in China, especially for countryside during heating period of winter, and polycyclic aromatic hydrocarbons （PAHs） are important in flue gas of the stove. By using dilution tunnel s...Domestic coal stove is widely used in China, especially for countryside during heating period of winter, and polycyclic aromatic hydrocarbons （PAHs） are important in flue gas of the stove. By using dilution tunnel system, samples of both gaseous and particulate phases from domestic coal combustion were collected and 18 PAH species were analyzed by GC-MS. The average emission factors of total 18 PAH species was 171.73 mg/kg, ranging from 140.75 to 229.11 mg/kg for bituminous coals, while was 93.98 mg/kg, ranging from 58.48 to 129.47 mg/kg for anthracite coals. PAHs in gaseous phases occupied 95% of the total of PAHs emission of coal combustion. In particulate phase, 3-ring and 4- ring PAHs were the main components, accounting for 80% of the total particulate PAHs. The total toxicity potency evaluated by benzo[a]pyrene-equivalent carcinogenic power, sum of 7 carcinogenic PAH components and 2,3,7,8-tetrachlorodibenzodioxin had a similar tendency. And as a result, the toxic potential of bituminous coal was higher than that of anthracite coal. Efficient emission control should be conducted to reduce PAH emissions in order to protect ecosystem and human health.展开更多
It is imperative to derive an appropriate cadmium (Cd) health risk toxicity threshold for paddy soils to ensure the Cd con-centration of rice grains meet the food safety standard. In this study, 20 rice cultivars from...It is imperative to derive an appropriate cadmium (Cd) health risk toxicity threshold for paddy soils to ensure the Cd con-centration of rice grains meet the food safety standard. In this study, 20 rice cultivars from the main rice producing areas in China were selected, and a pot-experiment was conducted to investigate transformation of Cd in paddy soil-rice system with 0 (CK), 0.3 mg kg–1 (T1) and 0.6 mg kg–1 (T2) Cd treatments in greenhouse. The results showed that Cd concentrations of rice grains existed signiifcant difference (P<0.05) in 20 rice cultivars under the same Cd level in soil. The Cd concentrations of rice grains of the CK, T1 and T2 treatments were in the range of 0.143–0.202, 0.128–0.458 and 0.332–0.806 mg kg–1, respectively. Marked differences of the ratios of Cd concentration for soil to rice grain (BCFs) and transfer factors (TFs, root to grain and straw to grain) among the tested cultivars were observed in this study. The bioconcentration factors (BCFgrain) and TFs of the 20 rice cultivars were 0.300–1.112 and 0.342–0.817, respectively. The TFs of Cd from straw to grain ranged from 0.366 to 1.71, with signiifcant differences among these 20 rice cultivars. The bioconcentration factors (BCFgrain) and TFs among the 20 rice cultivars ranged from 0.300–1.112 and 0.342–0.817, respectively. The species-sensitivity distribu-tion (SSD) of Cd sensitivity of the rice species could be iftted wel with Burr-III (R2=0.987) based on the data of BCFs. The toxicity threshold of Cd derived from SSD for the paddy soil was 0.507 mg kg–1 in the present study.展开更多
AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VAR...AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.展开更多
To investigate the environmental quality of the urban surface soil in Yinchuan City, the capital of Ningxia Hui Autonomous Region （Ningxia）, China, we sampled surface soil and measured the concentrations of 8 toxic ...To investigate the environmental quality of the urban surface soil in Yinchuan City, the capital of Ningxia Hui Autonomous Region （Ningxia）, China, we sampled surface soil and measured the concentrations of 8 toxic metals （Pb, Cr, Cu, Zn, Co, Bi, Ni and V） using X-ray fluorescence spectrometry. The enrichment characteristics and sources of these toxic metals in the soil were analyzed by the enrichment factor （EF） and multivariate statistical analysis. The results showed that the mean concentrations of these toxic metals in the soil samples were 25.0, 109.1, 16.8, 26.0, 37.2, 2.7, 25.3 and 59.9 mg/kg for Pb, Cr, Cu, Zn, Co, Bi, Ni and V, respectively, which were 1.2, 1.8, 0.8, 0.4, 3.2, 8.7, 0.7 and 0.8 times of the corresponding background values of Ningxia soil, respectively. The variations of Pb, Zn, Co, Bi and Ni concentrations in the surface soil of Yinchuan were larger than those of the other metals. Our results also showed that the toxic metals investigated in the soil had different enrichment levels. Both Co and Bi were significantly enriched, whereas Cr was only moderately enriched in the soil. There was a deficiency or minimal enrichment of the other toxic metals in the soil. Source analysis results based on the concentration, enrichment characteristics and multivariate statistical analysis indicated that Cr, V and Ni originated from a combination of fossil fuel combustion, traffic pollution and natural occurrence. Pb, Cu and Zn were predominantly derived from natural and traffic sources, while Co and Bi primarily originated from construction sources.展开更多
Hydroxylated multi-walled carbon nanotubes(h-MWCNTs) and carboxylated MWCNTs(c-MWCNTs)have potential applications in biomedicine, but their toxicity to human endothelial cells under stressed conditions associated with...Hydroxylated multi-walled carbon nanotubes(h-MWCNTs) and carboxylated MWCNTs(c-MWCNTs)have potential applications in biomedicine, but their toxicity to human endothelial cells under stressed conditions associated with chronic diseases was less studied in vitro. This study stressed human umbilical vein endothelial cells(HUVECs) with ER stress inducer thapsigargin(TG), and investigated the toxicity of h-MWCNTs and c-MWCNTs to normal and stressed HUVECs. h-MWCNTs and c-MWCNTs modestly reduced cellular viability, significantly promoted soluble ICAM-1(sICAM-1),soluble VCAM-1(sVCAM-1) as well as intracellular ROS, and decreased the expression of transcription factor KLF2 and KLF4. Pre-treatment with TG significantly reduced cellular viability, promoted IL-6 and THP-1 monocyte adhesion, and increased the expression of a panel of ER stress genes. ANOVA indicated no interaction between MWCNTs and TG pre-treatment on most of the endpoints. It was concluded that the toxicity of h-MWCNTs and c-MWCNTs to HUVECs might not be exacerbated by ER stress展开更多
Human health risks assessment were estimated by determining the nature and probability of adverse health effects in the North region’s populations who are now exposed to arsenic from drinking water or will be exposed...Human health risks assessment were estimated by determining the nature and probability of adverse health effects in the North region’s populations who are now exposed to arsenic from drinking water or will be exposed in the future. Several questions were addressed in this study: what types of health problems may be caused by arsenic from drinking water? What is the chance that people will experience health problems when exposed to different levels of arsenic? What arsenic level are people exposed to and for how long? To answers these questions we have first identified the hazard by evaluating arsenic concentration in thirty-four (34) bore-hole water points among the region based on the assumption of clinical cases related to drinking water. Arsenic concentration ranged from 0 up to 87.8 micrograms per liter. Next we assessed the dose-response of exposure to arsenic. Dose-response relationship describes how the likelihood and severity of adverse health effects are related to the amount and condition of exposure to arsenic. This required us to choose toxicity reference values (TRVs) above which adverse effects may occur for noncarcinogenic and for carcinogenic effects. Exposure factors have been calculated in two scenarios: people from 0 to 14 years old and people from 15 to 70 years. Exposure has been estimated indirectly through consideration of measured concentrations of arsenic in drinking water. This study show that people in the Yatenga, Zondoma and Passore provinces are at very high risk for developing several pathologies such as hyper pigmentation, keratosis, cancer, etc. due by chronic exposure to arsenic in drinking water.展开更多
文摘Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.
基金supported by the National Basic Research Program (973) of China (No. 2010CB429003)the National Natural Science Foundation of China (No.21077010)the Fok Ying-Tong Education Foundation,China (No. 121077)
文摘To advance the knowledge of the environmental fate of sulfamethoxazole （SMX）, we systematically investigated the effects of natural water constituents and synthetic substances （i.e., TiO2 nanoparticles （nTiO2） and Ti-doped ^-Bi203 （NTB）） on the photodegradation kinetics of SMX under xenon lamp irradiation. The photolysis of SMX in aqueous solution followed first-order kinetics. Our results showed that higher concentrations of SMX, fulvic acid, suspended sediments, NTB and higher pH value decreased the photodegradation rates of SMX, whereas H202 improved the SMX photodegradation. TiO2 nanoparticles had a dual effect on pbotodegradation due to their photocatalytic activity and photoabsorption of photons. No intermediates more toxic toward Vibrio fischeri than SMX were produced after direct photolysis and photocatalytic degradation for 3 hr. The photolysis of SMX involved three pathways： hydroxylation, cleavage of the sulfonamide bond, and fragmentation of the isoxazole ring. This study lays the groundwork for a better understanding of the environmental fate of SMX.
基金supported by the Natural Science Foundation of China(No.41275135,41105090)the National High Technology Research and Development Program(863)of China(No.2012AA063506)the Open Foundation of Environmental Simulation and Pollution Control State Key Laboratories(Peking University)
文摘Domestic coal stove is widely used in China, especially for countryside during heating period of winter, and polycyclic aromatic hydrocarbons （PAHs） are important in flue gas of the stove. By using dilution tunnel system, samples of both gaseous and particulate phases from domestic coal combustion were collected and 18 PAH species were analyzed by GC-MS. The average emission factors of total 18 PAH species was 171.73 mg/kg, ranging from 140.75 to 229.11 mg/kg for bituminous coals, while was 93.98 mg/kg, ranging from 58.48 to 129.47 mg/kg for anthracite coals. PAHs in gaseous phases occupied 95% of the total of PAHs emission of coal combustion. In particulate phase, 3-ring and 4- ring PAHs were the main components, accounting for 80% of the total particulate PAHs. The total toxicity potency evaluated by benzo[a]pyrene-equivalent carcinogenic power, sum of 7 carcinogenic PAH components and 2,3,7,8-tetrachlorodibenzodioxin had a similar tendency. And as a result, the toxic potential of bituminous coal was higher than that of anthracite coal. Efficient emission control should be conducted to reduce PAH emissions in order to protect ecosystem and human health.
基金support of the National Natural Science Foundation of China (41271490, 21077131)
文摘It is imperative to derive an appropriate cadmium (Cd) health risk toxicity threshold for paddy soils to ensure the Cd con-centration of rice grains meet the food safety standard. In this study, 20 rice cultivars from the main rice producing areas in China were selected, and a pot-experiment was conducted to investigate transformation of Cd in paddy soil-rice system with 0 (CK), 0.3 mg kg–1 (T1) and 0.6 mg kg–1 (T2) Cd treatments in greenhouse. The results showed that Cd concentrations of rice grains existed signiifcant difference (P<0.05) in 20 rice cultivars under the same Cd level in soil. The Cd concentrations of rice grains of the CK, T1 and T2 treatments were in the range of 0.143–0.202, 0.128–0.458 and 0.332–0.806 mg kg–1, respectively. Marked differences of the ratios of Cd concentration for soil to rice grain (BCFs) and transfer factors (TFs, root to grain and straw to grain) among the tested cultivars were observed in this study. The bioconcentration factors (BCFgrain) and TFs of the 20 rice cultivars were 0.300–1.112 and 0.342–0.817, respectively. The TFs of Cd from straw to grain ranged from 0.366 to 1.71, with signiifcant differences among these 20 rice cultivars. The bioconcentration factors (BCFgrain) and TFs among the 20 rice cultivars ranged from 0.300–1.112 and 0.342–0.817, respectively. The species-sensitivity distribu-tion (SSD) of Cd sensitivity of the rice species could be iftted wel with Burr-III (R2=0.987) based on the data of BCFs. The toxicity threshold of Cd derived from SSD for the paddy soil was 0.507 mg kg–1 in the present study.
基金Supported by VA HSR&D MERIT Award IIR,No.14-048-3 for Dr Caplansupported by a VA GME Enhancement Award
文摘AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.
基金supported by the National Natural Science Foundation of China (41271510, 41461098)the Fundamental Research Funds for the Central Universities of China (GK201601009, 2017TS027)
文摘To investigate the environmental quality of the urban surface soil in Yinchuan City, the capital of Ningxia Hui Autonomous Region （Ningxia）, China, we sampled surface soil and measured the concentrations of 8 toxic metals （Pb, Cr, Cu, Zn, Co, Bi, Ni and V） using X-ray fluorescence spectrometry. The enrichment characteristics and sources of these toxic metals in the soil were analyzed by the enrichment factor （EF） and multivariate statistical analysis. The results showed that the mean concentrations of these toxic metals in the soil samples were 25.0, 109.1, 16.8, 26.0, 37.2, 2.7, 25.3 and 59.9 mg/kg for Pb, Cr, Cu, Zn, Co, Bi, Ni and V, respectively, which were 1.2, 1.8, 0.8, 0.4, 3.2, 8.7, 0.7 and 0.8 times of the corresponding background values of Ningxia soil, respectively. The variations of Pb, Zn, Co, Bi and Ni concentrations in the surface soil of Yinchuan were larger than those of the other metals. Our results also showed that the toxic metals investigated in the soil had different enrichment levels. Both Co and Bi were significantly enriched, whereas Cr was only moderately enriched in the soil. There was a deficiency or minimal enrichment of the other toxic metals in the soil. Source analysis results based on the concentration, enrichment characteristics and multivariate statistical analysis indicated that Cr, V and Ni originated from a combination of fossil fuel combustion, traffic pollution and natural occurrence. Pb, Cu and Zn were predominantly derived from natural and traffic sources, while Co and Bi primarily originated from construction sources.
基金financially supported by College Outstanding Young and Middle-aged Innovative Research Team Project of HubeiProvince (No. T201717)the Health and Family Planning Commission Scientific Research Project of Hubei Province (No. WJ2017Z027)
文摘Hydroxylated multi-walled carbon nanotubes(h-MWCNTs) and carboxylated MWCNTs(c-MWCNTs)have potential applications in biomedicine, but their toxicity to human endothelial cells under stressed conditions associated with chronic diseases was less studied in vitro. This study stressed human umbilical vein endothelial cells(HUVECs) with ER stress inducer thapsigargin(TG), and investigated the toxicity of h-MWCNTs and c-MWCNTs to normal and stressed HUVECs. h-MWCNTs and c-MWCNTs modestly reduced cellular viability, significantly promoted soluble ICAM-1(sICAM-1),soluble VCAM-1(sVCAM-1) as well as intracellular ROS, and decreased the expression of transcription factor KLF2 and KLF4. Pre-treatment with TG significantly reduced cellular viability, promoted IL-6 and THP-1 monocyte adhesion, and increased the expression of a panel of ER stress genes. ANOVA indicated no interaction between MWCNTs and TG pre-treatment on most of the endpoints. It was concluded that the toxicity of h-MWCNTs and c-MWCNTs to HUVECs might not be exacerbated by ER stress
文摘Human health risks assessment were estimated by determining the nature and probability of adverse health effects in the North region’s populations who are now exposed to arsenic from drinking water or will be exposed in the future. Several questions were addressed in this study: what types of health problems may be caused by arsenic from drinking water? What is the chance that people will experience health problems when exposed to different levels of arsenic? What arsenic level are people exposed to and for how long? To answers these questions we have first identified the hazard by evaluating arsenic concentration in thirty-four (34) bore-hole water points among the region based on the assumption of clinical cases related to drinking water. Arsenic concentration ranged from 0 up to 87.8 micrograms per liter. Next we assessed the dose-response of exposure to arsenic. Dose-response relationship describes how the likelihood and severity of adverse health effects are related to the amount and condition of exposure to arsenic. This required us to choose toxicity reference values (TRVs) above which adverse effects may occur for noncarcinogenic and for carcinogenic effects. Exposure factors have been calculated in two scenarios: people from 0 to 14 years old and people from 15 to 70 years. Exposure has been estimated indirectly through consideration of measured concentrations of arsenic in drinking water. This study show that people in the Yatenga, Zondoma and Passore provinces are at very high risk for developing several pathologies such as hyper pigmentation, keratosis, cancer, etc. due by chronic exposure to arsenic in drinking water.
