Objective To investigate the pollution status of algae and microcystin(MC)in Dianshan Lake,Shanghai City and Poyang Lake,Jiangxi Province.Methods Water samples were collected from different sites of the above lakes,as the pretreatment of intracellular and extracellular microcystins was finished,MC-LR concentration was detected by ELISA.Results The proportion of Cyanobacteria in Dianshan Lake was 38.8% and 68.2% respectively,the mean content of MC was 281.78 and 1 145.77 pg/ml respectively.In Poyang Lake,the proportion of Cyanobacteria was 48.9% and 73.7% respectively,the mean content of MC was 80.53 and 405.65 pg/ml respectively.In the same water-blooming lake,MC content was significantly lower in July than that in October(P

Objective To explore the regulatory effect of apigenin on the blood pressure of the spontaneous hypertension rat(SHR) rats and the possible mechanism.Methods The case groups of rats were fed with different dosage of apigenin(0.03,0.05,0.11 g/kg) by gavage for 4 consecutive weeks,while the control groups were treated with equal cubage of oil.The body weight,heart rate,blood pressure were measured every week.Results After 4 weeks of treatment with apigenin,the blood pressure of SHR in all doses groups decreased significantly;besides,apigenin could reduce the content of ET-1 and AngII,however,it didn't change NOS activity.Conclusion Apigenin has a regulatory effect on blood pressure,its lowest effective dose is 0.03 g/kg bw and it may decrease the blood pressure through reducing the content of ET-1 and AngII,not through the NO/NOS pathway.

OBJECTIVETo assess dietary exposure of diethylhexyl phthalate(DEHP) among Chinese population, including general population, children aged 2-6 years, adolescent aged 7-12, young people aged 13-17, adults aged 18-59 years old as well as older people aged 60 and above and its health risk.

METHODSA total of 6 650 food samples were collected during 2011 to 2013 from 140 local markets of 14 provinces in China, which covered major foods in China. Samples were detected by GC-MS and categorized into 22 food groups. Food consumption data were taken from China National Nutrition and Health Survey performed in 2002 including 68 959 subjects. Mean concentrations of DEHP in food were combined with individual food consumption data to estimate dietary exposure, and food contributors to dietary DEHP intake were also calculated. Then, the exposure was compared with the tolerable daily intake (TDI, 50 µg·kg(-1)-d(-1)) of DEHP.

RESULTSDEHP level in foods (n = 6 650) was in the range of not detected to 43.80 mg/kg. Mean dietary intakes of DEHP in general population was 2.07 (95% CI: 0.06-4.09) µg·kg(-1)·d(-1), accounting for 4.14 percent of TDI (50 µg·kg(-1)·d(-1)). Mean dietary intake for population aged 2-6, 7-12, 13-17, 18-59 as well as elderly aged 60 and above were 3.92 (95% CI: 0.83-7.01), 3.02 (95% CI: 0.69-5.36), 2.17 (95% CI: 0.54-3.81), 1.83 (95% CI: 0.46-3.21) and 1.66 (95% CI: 0.38-2.94) µg·kg(-1)·d(-1) respectively. The 97.5 percentile intakes in the general populations was 4.73 µg·kg(-1)·d(-1), accounting for 9.46% of TDI. Main food sources of DEHP were rice (28.4% (0.59/2.07)), melon solanaceous vegetables (14.7% (0.30/2.07)) and flour (13.2% (0.27/2.07)) for the general population.

CONCLUSIONThe results suggested that dietary exposure to DEHP among Chinese population was lower than tolerable daily intake of DEHP and there were no health concerns based on generally accepted exposure limits. Rice, melon solanaceous vegetables and flour were main food contributors of DEHP dietary intake for Chinese populations.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; China ; Diet ; Diet Surveys ; Diethylhexyl Phthalate ; Flour ; Food ; Food Contamination ; Gas Chromatography-Mass Spectrometry ; Humans ; Middle Aged ; Oryza ; Risk Assessment ; Vegetables

Objective:To study the incidences of vitamin K 1 and K 2 deficiency (VKD) in umbilical cord blood (UBC) of neonates and the dynamic changes and influencing factors of serum vitamin K 1 levels after preventive vitamin K 1 supplementation. Methods:From January 2021 to June 2022, neonates born in the Obstetrics Department of our hospital were prospectively enrolled and the levels of vitamin K 1 and K 2 in UBC and serum vitamin K 1 levels at 14 d and 28 d after vitamin K 1 supplementation were measured. The neonates were assigned into hospitalization group and healthy group and further assigned into early-preterm, late-preterm and full-term groups based on gestational age (GA). The incidences of VKD of different GA were studied. Dynamic changes of vitamin K 1 levels were calculated. Multivariate logistic regression was used to analyze the influencing factors of vitamin K 1 levels in hospitalization group at 28 d. Results:A total of 100 neonates were included. 80 neonates were hospitalized, including 25 early-preterm, 25 late-preterm and 30 full-term. 20 were healthy full-term neonates. No significant differences existed in the incidences of VKD of different GA ( P>0.05), however, the overall incidences were high (82.0% and 84.0%, respectively). After preventive vitamin K 1 supplementation, the levels of vitamin K 1 in full-term and preterm groups at 14 d were higher than at birth and 28 d. The levels of vitamin K 1 in hospitalized full-term neonates at 14 d and 28 d were higher than hospitalized preterm neonates. The levels of vitamin K 1 at 28 d in healthy group was significantly higher than hospitalization group ( P<0.05). Multivariate logistic regression analysis showed that maternal complications during pregnancy ( OR=5.889, 95% CI 1.621-21.399, P=0.007) and neonatal antibiotic use ( OR=5.615, 95% CI 1.833-17.221, P=0.003) were risk factors and formula feeding ( OR=0.389, 95% CI 0.193-0.786, P=0.008) was a protective factor for VKD. Conclusions:VKD is common in neonates. The serum vitamin K 1 level increases significantly after preventive vitamin K 1 supplementation. The vitamin K 1 levels of hospitalized full-term neonates at 14 d and 28 d are higher than hospitalized preterm neonates. The levels of vitamin K 1 at 28 d in hospitalized neonates are influenced by feeding methods, maternal complications during pregnancy and neonatal antibiotic use.

Food toxicology plays a crucial role in supporting scientific and technical aspects of food safety risk assessment.However,traditional methods relying on animal testing are becoming increas-ingly inadequate for identifying and evaluating emerging foods and unknown risks.There is a strong push worldwide towards the development of new approach methodologies(NAMs)based on non-animal testing methods.Policies and regulations related to NAMs are being standardized gradually in the European Union,the United States,and China.Some progress has also been made in applying these methodologies in food toxicology research in China.For instance,within the"Food Toxicology Program"at the National Center for Food Safety Risk Assessment,high-content and high-throughput in vitro hazard identification models employing model organisms like human macrophages,hepatocytes,adipocytes,embryonic stem cells,and zebrafish,as well as Toxicological Thresholds of Concern and quantitative in vitro to in vivo extrapolation based on physiologically-based toxicokinetic models have been estab-lished and applied.Nonetheless,new toxicological hazard identification technologies still face challenges such as inadequate elucidation of toxic mechanisms,insufficient collaborative research efforts,and inef-ficient translation of these findings into practical applications.

Objective: To explore the characteristics of adverse drug reactions (ADRs) in a grade three class A hospital to provide reference for rational drug use and reduction of ADRs. Methods: The new and serious ADRs reported during 2014 and 2016 were sta-tistically analyzed in terms of the report type, age, gender, administration route, drug variety and involving system. Results: The new and serious ADR reports reached to 400 cases, which accounted for 64. 52% of the total reports. Of the 400 ADR reports,there were 34. 25% distributed in the 60-74-year old. The proportion of male and female in the ADRs was basically equal, while that of male (50. 25% ) was slightly higher than that of female (49. 75% ). There were 57. 00% of ADRs caused by intravenous administration, and 31. 25% caused by anti-infective drugs, in which cephalosporins accounted for the most (32. 00% ). The most common manifesta-tion of ADR was damage to skin and its appendages, which accounted for 33. 00% , followed by the damage to gastrointestinal system (15. 50% ) and hepatorenal function (14. 00% ). Conclusion: Great attention should be paid to monitoring and reporting ADRs in our hospital, and drugs should be rationally used so as to reduce the occurrence of ADRs.

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

OBJECTIVE To explore the applicablity of 'BlueScreen HC'(BSHC),a high throughput genotoxicity screening system based on human growth arrest and DNA damage inducible 45α(GADD45α)gene,in detecting the genotoxicity of migrants mixtures from food contact materials(FCM).METHODS The 2000 bp sequence upstream of the open reading frame of human GADD45α gene was used as the promoter to construct the lentiviral plasmid pEZX-LvPG04,which was double labeled by purinamycin and Gausluciferase(Gluc),and the lentiviral plasmid was infected with human lymphoblastocyte TK6 to obtain a stable transmutation cell line TK6-Gluc.Methyl methylate(MMS)at concentrations of 0,1.56,3.13,6.25,12.5,25.0 and 50.0 mg·L-1 was selected as the genotoxin without liver S9,cyclophosphamide(CTX)0,0.78,1.56,3.13,6.25,12.5,25.0 mg·L-1 was selected as the pre-genotoxin with liver S9,and dimethyl sulfoxide(DMSO)0,0.35,0.69,1.38,2.75,5.5 and 11.0 g·L-1 was selected as the non-genotoxin.The constructed BSHC was verified with the above known genetic positive and negative substance respectively.Polybutyleneadipate-co-terephthalate(MS/PBAT)was tested using 4% (V/V)acetic acid,and 10%,20%,50% and 95% (V/V)ethanol as food simulants at 40℃for 24 hours to obtain 5 multi-component migrants of MS/PBAT that were obtained by using DMSO as a solvent.TK6-Gluc cells were treated with 5 multi-component migrants of MS/PBAT at concentrations of 0,0.38,0.76,1.53,3.05,6.10 and 12.20 g·L-1 with or without liver S9.Cells were treated without liver S9 for 48 h.Cells treated with liver S9-mix were incubated for 3 h at a final concen-tration of 1% (V/V)liver S9 before being washed and re-suspended in fresh recovery media for another 45 h.After exposure,the cell viability was detected using the CCK-8 cell activity kit,and the Gluc Lumi-nescence in the medium was detected with Secrete-PairTM Gaussia Luciferase Assay Kit.In addition,the mutagenicity on Salmonella typhimurium TA98 and TA100 was detected by micro-fluctuation Ames test with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1.The in vitro mammalian cell chromosome aberration test was performed on CHL cells with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1 to detect the chromosomal aberration.The results of genotoxicity were compared with those of BSHC.RESULTS The lowest effect centra-tion(LEC;<80% relative cell viability)and the coytotoxicity(<30% relative cell viability)was defined.A positive genotoxicity result threshold was determined at 1.8-fold relative induction.For the liver S9 protocol,the same process was followed,and the decision threshold derived was 1.5-fold relative Gluc induction.It is considered as genetic substance only when a positive genotoxicity result was reached and there was no cytotoxicity.Compared with the vehicle control group,no genotoxicity was observed at all concentration of DMSO by BSHC.MMS 12.5,25.0 and 50.0 mg·L-1 produced genotoxicity without liver S9 while CTX 6.25,12.5 and 25.0 mg·L-1 produced genotoxicity with liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1,and in 50% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1 without liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups,and no high expression of Gluc was observed.Therefore,none of the 5 multi-component migrants produced genotoxicity without liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1,and in 4% acetic acid migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1 with liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups.No high expression of Gluc was observed.There-fore,none of the 5 multi-component migrants produced genotoxicity with liver S9.In the micro fluctua-tion Ames test,when 5 multi-component migrants of MS/PBAT were treated with concentrations of 3.05 and 12.20 g·L-1 on TA98 and TA100 strains,there was no significant difference in the number of muta-genic positive wells compared with DMSO control group with or without liver S9,indicating that no mutagenic effect was produced.When CHL cells were treated with 5 multi-component migrants of MS/PBAT at concentration of 3.05 and 12.20 g·L-1,compared with DMSO control group,there was no signifi-cant difference in chromosome aberration rate of CHL cells with or without liver S9.CONCLUSION BSHC based on GADD45α gene has been established,which can be used for in vitro genotoxicity eval-uation of migrants mixtures of FCM,but further exploration of its minimum effective concentrations is still needed,and more types of mixtures need to be applied for further validation.

BACKGROUND: Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models. METHOD: In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs. RESULTS: From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models. CONCLUSION Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.
Animals ; Benzhydryl Compounds ; toxicity ; Diethylstilbestrol ; toxicity ; Dose-Response Relationship, Drug ; Drug Interactions ; Endocrine Disruptors ; toxicity ; Estrogens ; toxicity ; Models, Theoretical ; Phenols ; toxicity ; Rats ; Rats, Sprague-Dawley ; Risk Assessment