Food additives are a kind of chemical substances added to food to enhance the taste,color and shelf life of food,and have become an indispensable part of the modern food industry.However,growing researches showed that synthetic chemicals used as food additives can be potentially harmful to health.Some food additives may be closely related to asthma,attention deficit hyperactivity disorder,heart disease,cancer,obesity and other health problems.In addition,some food additives may also interfere with hormone secretion,affect growth and development,and affect the healthy growth of children.This study reviews the damage effects of various food additives,such as preservatives,antioxidants,and colorants on body,and proposes the need to improve the safety evaluation of food additives from the perspective of the combined action of chemicals,in order to provide a scientific basis for food safety supervision and consumer health protection.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.

Objective To establish an ultra-high performance liquid chromatography(UPLC)fingerprint and multi-index content determination method of Siraitiae fructus standard decoction.Methods 15 batches of Siraitiae fructus from different producing areas were collected,Siraitiae fructus standard decoction was prepared according to Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules,and the extract rate was calculated.UPLC was used to establish the fingerprint of 15 batches of Siraitiae fructus standard decoction and determine the contents of 11-O-mogroside V,kaempferitrin and mogroside V,which were the main effective components.The chemometrics analysis was used to evaluate the quality of Siraitiae fructus standard decoction and find possible quality markers.Results The extraction rate of 15 batches Siraitiae fructus standard decoction ranged from 24.79％to 34.95％.There were 16 common peaks in the fingerprint,and 4 components were identified.The Siraitiae fructus standard decoction was divided into 2 categories by chemometrics analysis,among which samples from Liuzhou,Guangxi were in one category and samples from Guilin,Guangxi were in another category.Seven differential markers were screened out under the condition of variable importance projection value,and the order was as follows:peak 8＞peak 7＞peak 5＞peak 12(kaempferitrin)＞peak 1＞peak 13＞peak 4.The contents of kaempferitrin,11-O-mogroside V and mogroside V in samples from Guilin,Guangxi were slightly higher than those in samples from Liuzhou,Guangxi.Conclusion The UPLC fingerprint and content determination method established in this study are feasible,which can provide a basis for the quality evaluation of Siraitiae fructus.The results of principal component analysis show that kaempferol is likely to become a quality marker of Siraitiae fructus.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

Objective:To establish UPLC fingerprint method of Buddlejae Flos standard decoction and determination method of acteoside and linarin.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddlejae Flos standard decoction. Similarity evaluation and clustering analysis were carried out on the fingerprints of Buddlejae Flos standard decoction; the chromatographic peaks of standard decoction were identified by mass spectrometry and compared with the reference materials; the contents of acteoside and linarin in Buddlejae Flos standard decoction were determined by HPLC.Results:There were 11 common peaks in the fingerprint of Buddlejae Flos standard decoction and 6 of them were identified. The similarity of the 17 batch samples was between 0.972 and 0.999. Clustering analysis classified 17 batches of Buddlejae Flos standard decoction into two categories; edgeworthia chrysantha standard decoction was identified by the method of fingerprint as counterfeit; the content determination results showed that the contents of acteoside and linarin in the standard decoction prepared from Buddlejae Flos of in Hubei and Sichuan Provinces were higher than others and were more stable.Conclusion:The method can be used to comprehensively evaluate the quality of Buddlejae Flos standard decoction and provide reference for establishing the quality standard of Buddlejae Flos dispensing granules.

Objective:To establish the fingerprints of Microctis Folium by ultra high performance liquid chromatography (UPLC); To determine the contents of three flavonoids in the Microctis Folium; To evaluate the quality difference of Microctis Folium from different producing areas. Methods:The fingerprints were performed on Agilent ZORBAX SB C18 column (2.1 mm×150 mm,1.8 μm). The mobile phase was acetonitrile - 0.1 % acetic acid solution with gradient elution at a flow rate of 0.30 ml/min. The column temperature was 30 ℃ and the detection wavelength was 315 nm. The common fingerprint peaks were identified by UPLC-mass spectrometry, and the identification results were confirmed by comparison of reference materials. Waters Cortecs T3 C18 chromatographic column (2.1 mm × 100 mm,1.6 μm) was used for content determination. The mobile phase was methanol-0.1 % formic acid solution with gradient elution at a flow rate of 0.35 ml/min. The column temperature was 30 ℃ and the detection wavelength was 339 nm. The contents of vitexin, isovitexin and narcissoside in 15 batches of Microctis Folium from different habitats were determine. Results:There were 11 common peaks in the fingerprint of Microctis Folium. Identified by mass spectrometry and confirmed by reference substance,10 chemical components were identified, including caffeic acid, p-hydroxycinnamic acid, ferulic acid, vitexin, isovitexin, kaempferol-3-O-rutoside, astragaloside, narcissoside, isorhamnetin-3-O-glucoside and linden glycoside. The similarity between the fingerprints of 15 batches of Microctis Folium and the control fingerprint was greater than 0.95, indicating that the overall similarity of the fingerprints of Microctis Folium from different producing areas was high. The total contents of three active components were 3.23-5.64 mg/g in Yangjiang City, Guangdong, 3.60-5.78 mg/g in Zhanjiang City, Guangdong, 4.68-5.73 mg/g in Yulin City, Guangxi and 3.87-5.21 mg/g in Wuzhishan City, Hainan . There was no significant difference in the content of three active components in different producing areas. Conclusion:The fingerprints and the determination method established in the study are stable and feasible, which can be used for the quality evaluation of Microctis Folium.

【Objective】 To investigate the predictive value of high preoperative neutrophile-lymphocyte ratio (NLR) for the prognosis of nonurothelial carcinoma of the bladder (NUBC) after radical cystectomy (RC). 【Methods】 Clinical and follow-up data of NUBC patients undergoing RC during Jan.2005 and Dec.2020 were collected. The optimal cut-off value of NLR was determined with the receiver operating characteristic (ROC) curve. The survival curve was drawn with Kaplan-Meier method to compare the differences in cancer specific survival (CSS) and overall survival (OS) between the high-NLR and low-NLR groups. The independent risk factors of CSS and OS were screened with Cox proportional hazard regression model. 【Results】 Of the 62 eligible cases,34 (54.8%) were diagnosed with adenocarcinoma,17 (27.4%) with squamous cell carcinoma, 6 (9.7%) with small cell carcinoma and 5 (8.1%) with sarcoma. Kaplan-Meier analysis results showed high NLR was associated with poor CSS (P=0.001) and OS (P<0.001). Cox regression results indicated that high NLR (HR=2.42, 95%CI: 1.12-5.23, P=0.025) and advanced pathologic tumor stage (HR=3.21, 95%CI:1.53-6.74,P=0.002) were independent risk factors of unfavorable CSS. Similarly, high NLR (HR=2.75, 95%CI: 1.35-5.56, P=0.005) and advanced pathologic tumor stage (HR=2.81, 95%CI:1.43-5.57, P=0.003) were independent risk factors of unfavorable OS. 【Conclusion】 As an independent risk factor of unfavorable CSS and OS in NUBC patients undergoing RC, high preoperative NLR is of great value in the prediction of long-term prognosis and may help to optimize individualized treatment.

Objective To investigate the clinical efficacy of low-dose plasma exchange (PE) combined with artificial liver in the treatment of acute-on-chronic liver failure (ACLF) and its effect on mortality rate after stratification. Methods A total of 272 ACLF patients who were admitted to Department of Infection and Hepatology, The First Affiliated Hospital of Kunming Medical University, from January 2018 to December 2020 were enrolled and divided into low-dose PE+double plasma molecular absorption system (DPMAS)/hemoperfusion (HP) group ( n =190) and medical treatment group( n =82). Laboratory markers were collected before and after treatment, and clinical outcome was compared between the two groups; stratified analysis (early stage, early-middle stage, late stage or types A, B, C) was performed for the two groups according to Diagnostic and treatment guidelines for liver failure (2018 edition), and all patients were followed up to observe general status and death at 12 weeks (short-term) and 48 weeks (long-term) after discharge. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the paired samples t -test was used for comparison before and after treatment; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Wilcoxon test was used for comparison before and after treatment; the chi-square test was used for comparison of categorical data between groups. Results Both low-dose PE combined with DPMAS/HP and medical treatment alone could reduce the levels of alanine aminotransferase (ALT), aspartate aminotransferase, total bilirubin (TBil), and blood ammonia and increase the level of albumin (Alb), and both groups had significant changes in these indices after treatment (all P < 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP better reduced ALT, TBil, and blood ammonia and improved Alb, with significant changes in these indices after treatment (all P < 0.05). Low-dose PE combined with DPMAS/HP could significantly reduce bile acid, international normalized ratio, neutrophil-lymphocyte ratio, and MELD score and increase platelet-to-white blood cell ratio (all P < 0.05), while medical treatment alone could not improve the above indices (all P > 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP could reduce the short-term mortality rate of ACLF patients, especially the short-term mortality rate of ACLF patients with early-stage, early-middle-stage or type A ACLF, and there were significant differences between the two groups (all P < 0.05). In the low-dose PE+DPMAS/HP group, the patients with early-stage ACLF had significantly lower short- and long-term mortality rates than those with late-stage ACLF, and the patients with type A ACLF had significantly lower short- and long-term mortality rates than those with type C ACLF (all P < 0.05). Conclusion Low-dose PE combined with DPMAS/HP has good clinical efficacy and can effectively reduce the short-term mortality rate of ACLF, especially the short-term mortality rate of patients with early-stage, early-middle-stage, or type A ACLF.

Objective:To establish the quality evaluation method of Perillae caulis formula granules based on the three kind of quality indexes of standard decoction. Methods:Eighteen batches of Perillae caulis were collected from different habitats according to different technical requirements, eighteen batches of standard decoction and three batches of formula granules were prepared and the paste-forming rates were calculated. The content of Caffeic acid and Rosmarinic acid were determined and calculated by Ultra High Performance Liquid Chromatography (UPLC). Then the fingerprints of standard decoction of and formula granules of Perillae caulis were established by UPLC . The similarity values of fingerprints between formula granules and standard decoction were calculated. Results:The average paste-forming rate of standard decoction was (7.16±1.97)%. The paste-forming rates of three batches of formula granules were 5.52%, 5.25% and 5.34%, respectively. The average content of Caffeic acid and Rosmarinic acid in standard decoction was (12.06±3.37)mg/g. The contents of three batches of formula granules were 5.52, 5.82, 5.77 mg/g, respectively. Seven common fingerprint peaks were identified in the fingerprints of standard decoction and formula granules, three of which were identified as Caffeic acid, N-Feruloyl Octopus amine and Rosmarinic acid by comparison of reference substance. The fingerprints similarity of Perillae caulis dispensing granules and standard decoction were 1.000, 0.995 and 0.997, respectively. Conclusions:The quality indexes of three batches of formulation granules are consistent with standard decoction. This method can provide basis for the establishment of quality standard of Perillae caulis dispensing granules.