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.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Currently,the ethical review model for organ donation and transplantation in domestic hospitals is generally characterized by suddenness,unpredictability,tight time,difficulty in convening meetings and training committee members,as well as generally low quality and efficiency of ethical review,which cannot meet clinical needs and cause the waste of some scarce resources.The team of the Clinical Application Center of Human Organ Transplantation and the Ethics Committee of the First People's Hospital of Kunming combine more than 10 years of review practice experience,as well as continuously explore and optimize the ethical review process and operating procedures for organ donation and transplantation.The special application has been approved and jointly developed with Soochow University and the Medical Ethics Committee of Fujian Province to build a full-process information software system management platform for organ ethical review of donation and transplantation,giving the full play the advantages of the review information system in improving work efficiency and review quality,facilitating full-process information management,and conducting online training and learning for committee members,with a view to providing a specialized practical model for addressing the difficulties and challenges related to ethical review of human organ donation and transplantation.

Objective To translate the Eating Behaviors Assessment for Obesity(EBA-O)and test its reliability and validity for providing an effective tool for brief and rapid clinical assessment of dietary behavior in obese patients.Methods The Chinese version of EBA-O was developed by Brislin's translation model for translation,back translation,cultural adaptation,and pilot investigation.Using convenience sampling method,200 obese patients who were admitted to the inpatient ward of the Weight Loss Center of a tertiary hospital in Beijing from April to June 2023 and planned to undergo weight loss metabolic surgery were selected as the research participants to test the reliability and validity of the Chinese version of EBA-O.Results The Chinese version of EBA-O includes 4 dimensions,with a total of 17 items.The Cronbach's α coefficient of the scale is 0.886;the Cronbach's αcoefficients of the dimensions are 0.770～0.866;the test-retest reliability of the scale is 0.881.The content validity index of the scale level is 0.980,and the content validity indexes of item level were 0.889～1.000.Totally 4 common factors were extracted through exploratory factor analysis,with a cumulative variance of 66.363％.Conclusion The Chinese version of EBA-O has good reliability and validity,and it can be used as a tool to evaluate the dietary behavior of obese patients undergoing weight loss metabolic surgery.

Objective:To comprehensively analyze the clinical characteristics,classification of causes,treatment methods,and outcomes of pediatric convulsions in the emergency department,providing a scientific basis for the diagnosis and treatment of pediatric convulsions and optimizing emergency management for these cases.Methods:The clinical data of 18 217 children with convulsions in the emergency department of Capital Institute of Pediatrics' Children's Hospital from January 1,2016 to December 31,2020 were retrospectively analyzed.Results:A total of 18 217 children were admitted to the emergency department due to convulsions,accounting for 2.3% of all visits.Among them,58.7% cases were male and 41.3% cases were female,with an average age of (2.00±0.03) years.The main age was 1 to 3 years old (54.2%).Generalized convulsions were the primary type (82.3%),with focal seizures accounting for 17.7%.Most convulsions lasted less than 5 minutes (82.4%),and approximately 55.2% of the patients could self-resolve.Febrile convulsions were the primary cause (69.2%),followed by benign convulsions with mild gastroenteritis (11.7%) and epilepsy (10.5%).Regarding treatment,54.0% of the children recovered without medication.In the triage system of "three zones and four levels," the usage rate of anticonvulsants in the red zone was 93.1%,with 21.6% requiring combined treatment.After treatment,48.2% of the children returned home,92.2% showed improvement or recovery,and the mortality rate was extremely low at only 0.03%.Conclusion:Febrile convulsions are the main cause of pediatric convulsions in the emergency department,and an efficient triage system play an important role in improving treatment response.Different treatment zones and outcomes vary,providing important reference for optimizing emergency management.

Objective To investigate the protective effect of curcumin (Cur) against arsenic-induced neuroimmune toxicity and the underlying molecular mechanisms in vivo. Methods Eighty SPF female C57BL/6 mice were randomly assigned to four groups: a control group, an arsenic-treated group, a Cur-treated group and an arsenic+Cur group, with 20 mice in each group. The control group received distilled water; the arsenic-treated group was given 50 mg/L NaAsO₂ in the drinking water; the Cur-treated group was gavaged with 200 mg/kg of curcumin for 45 days; and the arsenic+Cur group received distilled water and was gavaged with 200 mg/kg of curcumin. Y-maze and Morris water maze experiments were conducted to assess the learning and memory ability of the mice. Western blot analysis was used to detect protein levels of blood-brain barrier tight junction proteins zonula occludens protein 1(ZO-1) and claudin 5, T lymphocyte subpopulation CD4 and CD8, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules JAK2 and STAT3. Real-time PCR was used to assess the mRNA levels of CD4⁺ T lymphocyte subsets type 1 T helper (Th1), Th2, Th17 and regulatory T cells (Treg) transcription factors and cytokines in hippocampus. Results Compared with the control group, the arsenic-treated group showed a significantly decreased correct rate, increased latency to reach the platform on the third and fifth days, and reduced times of crossing the platform. The expression of ZO-1 and claudin 5 protein decreased significantly, and the protein levels of CD4 and CD8 were up-regulated. The mRNA levels of Th1, Th17, and Treg transcription factor T-box expressed in T cell(T-bet), retinoid-related orphan receptor gamma t(RORγt), and forkhead box protein 3(FOXP3) in the arsenic-treated group were decreased. Th1 and Th17 cytokines interferon γ(IFN-γ) and interleukin 17(IL-17) were markedly decreased. In contrast, the mRNA levels of the Th2 transcription factor GATA binding protein 3(GATA3) and cytokine IL-4 in arsenic-treated group were higher than those in the control group. Furthermore, the protein levels of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) increased. Compared with the arsenic-treated group, the arsenic+Cur group demonstrated a significantly increased correct rate, decreased latency to reach the platform on the third and fifth days, and increased times of crossing the platform. The protein expression levels of ZO-1 and claudin 5 increased significantly, and the protein levels of CD4 and CD8 were down-regulated. The mRNA levels of Th2 transcription factor GATA3 and cytokine IL-4 were decreased. The mRNA levels of Th17 transcription factor RORγt and cytokine IL-17 were markedly increased. Furthermore, the protein levels of p-JAK2 and p-STAT3 decreased. Conclusion Through inhibiting the JAK2/STAT3 signaling pathway, curcumin could improve arsenic-induced decline in learning and memory abilities in mice, reverse the destruction of blood-brain barrier permeability of innate immune system components in arsenic-exposed mice, and antagonize arsenic-induced increase in the number of renal CD4 and CD8 molecule as well as the imbalance of CD4⁺ T lymphocyte subsets (Th1, Th2, Th17 and Treg), ultimately counteracting arsenic-induced neurotoxicity.
Animals ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Female ; Curcumin/pharmacology* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Mice ; Arsenic/toxicity*

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

OBJECTIVE: To investigate the effects of combined exposure to di(2-ethylhexyl) phthalate(DEHP) and bisphenol A(BPA) on glucose metabolism in female rats during gestational and lactation periods, and its possible mechanism. METHODS: Twenty-four specific pathogen free pregnant SD rats were randomly divided into control group, DEHP group, BPA group, and combined exposure group, with 6 rats in each group. From the 5 th day of gestation to the 21 st day after birth of the offspring, the rats in the DEHP group were treated with DEHP 600 mg/kg body weight(bw); rats in BPA group were treated with 80 mg/kg bw BPA, and rats in combined exposure group were treated with 600 mg/kg bw DEHP and 80 mg/kg bw BPA by intragastric perfusion, while the rats in the control group were given the same amount of corn oil, once per day. After exposure, maternal rats were sacrificed immediately. The levels of glucose metabolism related indicators in liver tissues and serum were examined, and the mRNA and protein expression of phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(AKT) signaling pathway related factors in liver tissues were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot. RESULTS: Except for the activity of phosphoenolpyruvate carboxykinase(PEPCK) in BPA group, the levels of liver glycogen and serum high density lipoprotein cholesterol(HDL-C) in rats of the 3 exposure groups decreased(P<0.05), while the activity of serum PEPCK and the level of low density lipoprotein cholesterol(LDL-C) increased(P<0.05) compared with rats in the control group. The levels of liver glycogen and serum HDL-C in the combined exposure group were lower than that in the BPA group(P<0.05), while the level of serum LDL-C were lower than that in DEHP group and BPA group(P<0.05). The levels of serum glycosylated serum protein, total cholesterol and triglyceride in the 4 groups were not statistically different when compared with each other(P>0.05). Except for the PI3 K protein in DEHP group, the mRNA and protein expression of PI3 K, AKT, and glucose transporter 4 in liver tissues of rats in the 3 exposure groups decreased(P<0.05), and the mRNA expression of forkhead box protein 1(Foxo1) decreased(P<0.05), but the protein expression of FOXO1 increased(P<0.05) compared with the control group. CONCLUSION: Exposure to DEHP or BPA during pregnancy and lactation can cause glucose metabolism disorders in rats. The combined exposure of DEHP and BPA has certain synergistic effect. This process may be achieved through the PI3 K/AKT signaling pathway.

OBJECTIVE: To investigate the mechanism of calcium ion(Ca~(2+))/calcineurin(CaN) signaling pathway in bisphenol A(BPA)-induced interleukin-6(IL-6) secretion in macrophages. METHODS: Raw 264.7 cells in logarithmic growth phase were divided into control group, activator group, BPA low-, medium-and high-dose groups and inhibitor group. The cells in control group were treated with 0.10% dimethyl sulfoxide. The activator group was treated with lipopolysaccharide at mass concentration of 2 mg/L. The 3 BPA groups were treated with BPA at final concentrations of 1, 10, or 100 μmol/L. Two sets of verapamil or tacrolimus(FK506) groups were given verapamil at the final concentration of 10 or 30 μmol/L; or final concentration of FK506 at 250 or 500 nmol/L. Then the cells were treated with final concentration of 100 μmol/L BPA. The cells were collected at 4, 12, and 24 hours. The mRNA expression of IL-6 and CaN at 4 and 12 hours were detected by real-time fluorescence quantitative polymerase chain reaction. The relative expression of IL-6 and CaN protein was detected at 24 hours by enzyme-linked immunosorbent assay, and the intracellular Ca~(2+) level was detected at 4 hours using a single-tube multi-function detector. RESULTS: At 12 hours, the mRNA expression of IL-6 in the 100 μmol/L BPA group was higher than that in control group, activator group and the 1 and 10 μmol/L BPA groups(P<0.05), and higher than that in the 10 and 30 μmol/L verapamil groups, and in the 250 and 500 nmol/L FK506 groups(P<0.05). The mRNA expression of CaN in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05), and higher than in 10 and 30 μmol/L verapamil groups(P<0.05). The relative expression of IL-6 protein in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05). The relative expression of CaN protein in 100 μmol/L BPA group and 10 and 30 μmol/L verapamil groups were higher than that in control group and activator group(P<0.05). The relative expression of CaN protein in the 10 and 30 μmol/L verapamil groups were lower than that in the 100 μmol/L BPA group(P<0.05). The intracellular Ca~(2+) level in the 100 μmol/L BPA group was higher than that in control group and activator group(P<0.05). The intracellular Ca~(2+) level in the 10 μmol/L verapamil group was lower than that in the 100 μmol/L BPA group(P<0.05). CONCLUSION: BPA might promote the secretion of IL-6 through Ca~(2+)/CaN signaling pathway in macrophages.

OBJECTIVE: To observe the hepatic injury induced by combined exposure to diethylhexyl phthalate( DEHP) and bisphenol A( BPA) in rats and explore the mechanism of oxidative stress. METHODS: Thirty-two specific pathogen free healthy male SD rats were randomly divided into control group,DEHP(750 mg/kg body weight) group,BPA(100 mg/kg body weight) group and combined exposure group,with 8 rats in each group. The rats were gavaged once per day,7 days per week,for 6 weeks. The changes of liver organ coefficient and histopathology were observed. The activities of superoxide dismutase( SOD), glutathione peroxidase( GSH-Px) and the levels of hydrogen peroxide( H2 O2),malondialdehyde( MDA) were detected by spectrophotometry. The relative mRNA expression of antioxidant gene nuclear factor erythroid-2 related factor 2( Nrf2),heme oxygenase-1( HO-1),glutamate cysteine ligase catalytic subunit( Gclc),thioredoxin reductase( Txnrd),superoxide dismutase 3( Sod3) and glutathione peroxidase 1( Gpx1) in liver tissue were examined by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The body weight of DEHP exposure group was lower than that of control group from the beginning of the 2 nd week( P < 0. 05),and the body weight of combined exposure group was lower than control group from the beginning of the 3 rd week( P < 0. 05). The liver mass and organ coefficients in DEHP group and combined exposure group were significantly higher than that of control group( P <0. 05). The results of pathology examination showed that there was necrosis of liver cells in DEHP group,vacuolar degeneration in cytoplasm of BPA group,and severe inflammatory cell infiltration in combined exposure group. The activity of SOD and GSH-Px of each exposure group was reduced( P < 0. 05),the H2 O2 level of each exposure group was increased(P < 0. 05),meanwhile the MDA level in the liver tissue of the BPA group and the combined exposure group increased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1 and Gpx1 in each exposure group were decreased( P < 0. 05),the relative mRNA expression of Gclc,Txnrd and Sod3 in DEHP group and mixed exposure group were decreased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1,Gclc,Txnrd and Sod3 in combined exposure group were decreased compared with the BPA group( P < 0. 05).CONCLUSION: Under the conditions of this study,DEHP and BPA alone or in combination could cause hepatic injury. The combined effect was greater than single effect. The effect of DEHP was greater than that of BPA. The liver injury induced by DEHP and BPA was related to Nrf2 signaling pathway.