Biological effects and toxicity mechanisms of polystyrene nanoplastics: A review / 环境与职业医学

Polystyrene nanoplastics (PS-NPs) are widely used in industry, pharmaceutical and consumer packaging materials, and medical products. The biological health impacts of PS-NPs are receiving increasing attention. Therefore, it is necessary to conduct a literature review of in vitro and in vivo experimental studies from a biological mechanism perspective. Based on the latest research results at home and abroad, this review introduced the characteristics and cell internalization of PS-NPs in cytotoxicity experiments, and summarized the effects of PS-NPs on cytotoxic targets such as mitochondria, lysosomes, proteins, and DNA. In addition, the influencing factors of the health effects of PS-NPs were analyzed from the aspects of physical and chemical properties and cell types. Finally, by discussing the current research hotspots of cytotoxicity mechanism and biological effects, it was anticipated to provide a reference for the health risk management and biological safety assessment of PS-NPs.

Comprehensive Evaluation of Health Status of Traditional Chinese Medicine Constitution based on Improved Radar Chart / 中医杂志

ObjectiveTo present the health status of traditional Chinese medicine （TCM） constitutions more intuitively and comprehensively based on improved radar chart. MethodsParticipants who completed a 26-week comprehensive intervention based on TCM constitution from February 2013 to January 2014 in Zhuhai branch of Guangdong Provincial Hospital of Chinese Medicine were included in the study. They were divided into groups according to gender and age， i.e. young， middle-aged， and elderly male and female groups. TCM constitution scale and health survey short form （SF-36） were used to evaluate the 9 basic TCM constitution types and quality of life at three time points， including pre-intervention （T1）， at 13-week intervention （T2）， and at 26-week intervention （T3）. The improved radar charts were drawn to visually present the comprehensive evaluation results on the health status of 9 TCM constitutions， and graphic features （area S value， perimeter L value） were extracted to construct a comprehensive health index for TCM constitutions （H value）. Spearman correlation analysis was used to analyze the correlation between H value and SF-36 total score. ResultsAmong the included 509 participants， there were 45 elderly male， 76 elderly female， 60 middle-aged male， 140 middle-aged female， 53 young male and 135 young female. The radar charts for comprehensive evaluation of TCM constitution health status showed that the total areas for all groups increased at T3 compared to T1， with the most significant increase in the young population. In the middle-aged population， the fan-shaped areas of certain constitutions decreased at T2 than T1. At T3， the radar chart shapes for females were more balanced than males in the same age group. By calculating the features of function graphs， it was found that the S， L， and H values for the elderly population were relatively higher than those for the middle-aged and young population with the same gender， and the young population increased by highest ratio. The values measured at T3 compared to T1 showed average increase of 26% for S value （11% for the middle-aged and 14% for the elderly）， 22% for L value （10% for the middle-aged and the elderly each）， and 22% for H value （10% for the middle-aged and 9% for the elderly）. The female had lower S and L values， as well as higher H value than the male of the same age group measured at T3. The correlation coefficient between the H value of all participants and the total SF-36 score was 0.662 （P＜0.01）. ConclusionThe comprehensive evaluation model for the health status of TCM constitution based on the improved radar chart constructed in this study can present the health status of TCM constitutions and intervention effectiveness more comprehensively and intuitively. It is suggested to regulate the constitution in pursuit of the dynamic balance of the constitution health status， as well as consider the parts from the whole， and put focus on the balance of nine TCM constitutions.

Global characterization of modifications to the charge isomers of IgG antibody / 药物分析学报

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quanti-tatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fraction-ated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor ac-counting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1 / 国际口腔科学杂志·英文版

Head and neck squamous cell carcinoma (HNSCC) still lacks effective targeted treatment. Therefore, exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC. Here, we reported that the expression levels of family with sequence similarity 64, member A (FAM64A) were significantly higher in HNSCC tissues and cell lines. In addition, FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC. Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells, and vice versa. Moreover, we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model. Mechanistically, a physical interaction was found between FAM64A and forkhead box protein M1 (FOXM1) in HNSCC cells. FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1, but also, more importantly, by modulating FOXM1 expression via the autoregulation loop. Furthermore, a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts. Taken together, our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC, and FAM64A might be a promising molecular therapeutic target for treating HNSCC.

The different effect of sleep quality on health-related quality of life among young and middle-aged people / 中华行为医学与脑科学杂志

Objective:To investigate the characteristics of the sleep quality and health-related quality of life (HRQoL), and analyze the different effects of sleep quality on HRQoL among young and middle-aged people.Methods:A cross-sectional study recruited 1 976 participants.All participants completed a self-designed questionnaire for the adults' general condition, the Pittsburgh sleep quality index (PSQI) and Short-Form health survey (SF-36). All participants were divided into 3 age groups: 18-29-year-old group( n=1 148), 30-44-year-old group( n=586) and 45-59-year-old group ( n=242). SPSS 23.0 software was used for statistical analysis.Chi-square test was used to analyze the general characteristics of the three age groups.Non-parametric test was used to analyze the scores of the three age groups in different dimensions of sleep quality. One-way ANOVA was used to analyze the mean scores of the three age groups in different dimensions of HRQoL. Stepwise regression analysis was used to analyze the effect of sleep quality on HRQoL among the three groups after control the confounding factors such as marital status, education, smoking, drinking and exercise habits and past medical history. Results:In terms of sleep quality, the total PSQI scores of 18-29-year-old, 30-44-year-old and 45-59-year-old groups(4(2, 6), 4(2, 6), 4(2, 6)) showed statistically significant differences ( Z=10.951, P=0.004). In terms of HRQoL, there were statistically significant differences in physical component summary scores (18-29-year-old: 82.51±12.62, 30-44-year-old: 80.72±13.63, 45-59-year-old: 82.04±13.07, F=3.667, P=0.026) and mental component summary scores(18-29-year-old: 76.09±15.46, 30-44-year-old: 77.20±16.14, 45-59-year-old: 81.82±14.14, F=13.649, P<0.001) among young and middle-aged people in different age groups.Regression analysis found that daytime dysfunction was an independent influencing factor for HRQoL in young and middle-aged population ( β=-0.308--0.425, all P<0.01). Sleep disorders significantly decreased Physical Component Summary of HRQoL in young-aged people ( β=-0.127--0.215, all P<0.01). The use of hypnotic drugs significantly reduced the scores in the physiological field in the young adults aged 30-44 ( β=-0.076, P<0.05). The duration of sleep significantly decreased the scores in the mental domain of young adults aged 30-44 ( β=-0.112, P<0.01). Subjective sleep quality was an independent factor that significantly decreased HRQoL in young adults aged 18-29 and 30-44 years ( β=-0.089--0.169, all P<0.01). Conclusion:Sleep quality and HRQoL of young and middle-aged people in different age groups show different characteristics.The effect of sleep quality on HRQoL is different among people in different ages.Taking targeted interventions for people of different ages to improve the sleep quality may be an effective way to improve their HRQoL.

Effect of ligustrazine on cardiac inflammation in rats with type 2 diabetes mellitus / 中国病理生理杂志

AIM: To study the effect of ligustrazine on the cardiacmyocyte lesion in rats with type 2 diabetes mellitus.METHODS: Male Wistar rats were injected with STZ via tail vein under high-glucose and high-fat feeding for 4 weeks to establish the animal model of type 2 diabetes mellitus.Ligustrazine at different doses was used to treat the diabetic rats.The body weight, blood glucose and the morphology of heart tissues were observed.The myocardial levels of IL-1β, IL-6 and TNF-α were detected by ELISA, and the protein expression of IKKβ and NF-κB in the myocardium was determined by Westeren blotting.RESULTS: Ligustrazine at high dose alleviated the body weight reduction and blood glucose elevation cause by diabetes, and reduced pro-inflammatory factors IL-1β, TNF-α and IL-6.Moreover, the protein expression of IKKβ and NF-κB was significant decreased by ligustrazine.CONCLUSION: Ligustrazine inhibits the myocardial inflammation caused by diabetes through anti-inflammatory pathway.

Effect of fluvastatin on expression of SGK1 and CTGF induced by aldosterone in rat mesangial cells / 中国病理生理杂志

AIM:To investigate the effect of fluvastatin on the expression of serum and glucocorticoid inducible kinase 1 ( SGK1) and connective tissue growth factor ( CTGF) induced by aldosterone ( Ald) in rat mesangial cells (GMCs). METHODS:GMCs were divided into (1) control group; (2) aldosterone group with different concentrations and times; (3) Ald (10 -7 mol/L) + spironolactone (10 -9 mol/L) group; (4) Ald (10 -7 mol/L) + LY294002 (20 ?mol/L) group; (5) Ald (10-7mol/L) +SB203580 (20 mmol/L) group; (6) the group of Ald (10-7mol/L) + fluvas-tatin at different concentrations (10-7,10-6,10-5 mol/L); (7) Ald (10 -7mol/L) + fluvastatin (10 -5mol/L) + mevalonate (10 -4 mol/L) group; (8) Ald (10 -7 mol/L) + fluvastatin (10 -5 mol/L) + FPP (farnesyl pyrophosphate,10-4 mol/L) group; (9) Ald (10 -7mol/L) + fluvastatin (10 -5 mol/L) + GGPP (geranylgerany pyrophosphate,10 -4 mol/L) group. The protein levels of SGK1 and CTGF were determined by Western blotting. The levels of fibronection (FN),monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) in the supernatants were determined by enzymelinked immunosorbant assay (ELISA). RESULTS:Aldosterone stimulated the protein expression of SGK1 and CTGF in cultured mesangial cells in a dose-dependent manner (P