The health effects associated with environmental pollutants remain one of the major public health issues at present. The research method focusing on the population as the research subjects is limited by reliable cohorts, and the research method targeting individual molecules cannot fully reflect the biological health effects under environmental pollutant stress. Using high-throughput multi-omics, machine learning, and epigenetic detection to conduct targeted research and joint analysis on cells, organoids, organs, animals, and humans in different biological dimensions will help provide data support for the study of potential targets and biological effects of environmental pollutants, providing a theoretical basis for the risk assessment and safety evaluation of environmental pollutants.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

Objective To study the protective effect and related mechanism of pterostilbene(PTE)on renal ischemia-reperfusion injury(IRI)in mice.Methods Twenty-four C57 mice were randomly divided into 4 groups(n=6),including the sham operation group(S group),the renal ischemia reperfusion group(IR group),the renal ischemia reperfusion+5 mg/kg PTE group(IR+PTE1 group)and the renal ischemia reper-fusion+10 mg/kg PTE group(IR+PTE2 group).Hematoxylin-eosin(HE)and TUNEL staining were used to evaluate renal tissue injury.Creatinine(Cr),blood urea nitrogen(BUN),malondialdehyde(MDA)in renal tissue,inflammatory cytokines tumor necrosis factor(TNF-α),interleukin(IL)-1β and IL-6 levels in serum were detected with relevant kits.The expression of Bcl-2 interacting protein 3(BNIP3)and microtubule-asso-ciated protein light chain(LC)-3 Ⅱ in kidney tissue was detected by Western blot.Results Compared with the S group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR group were increased,renal tu-bule injury score and apoptosis index were increased,and expressions of BNIP3 and LC-3 Ⅱ were down-regula-ted,with statistical significance(P＜0.05).Compared with the IR group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR+PTE1 group were decreased,renal tubule injury score and apoptosis index were decreased,and expressions of BNIP3 and LC-3 Ⅱ were up-regulated,with statistical significance(P＜0.05).Compared with the IR+PTE1 group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR+PTE2 group were decreased,renal tubule injury score and apoptosis index were decreased,and expres-sions of BNIP3 and LC-3 Ⅱ were up-regulated,with statistical significance(P＜0.05).Conclusion PTE has protective effect on renal IRI in mice.

Objective:To construct a novel cuproptosis-related gene signature (CRGS) for prediction of prognosis, immunotherapy response and drug sensitivity in patients with hepatocellular carcinoma (HCC).Methods:Data materials for this study were obtained from the international cancer genome consortium (ICGC), the cancer genome atlas (TCGA) database and Migort210 database, and protein expression profiles were obtained from the human protein atlas image classification database. Based on the TCGA cohort, the least absolute shrinkage and selection operator algorithm was applied to construct the CRGS and calculate the risk score for each HCC patient. HCC patients were grouped according to the median risk score: HCC patients in the TCGA cohort were divided into a high-risk group TCGA and a low-risk group TCGA with 184 cases in each group; HCC patients in the ICGC cohort were divided into a high-risk group ICGC and a low-risk group ICGC with 116 cases in each group. Patients in the Migort210 cohort were divided into a responder group ( n=68) and a non-responder group ( n=230) based on their response to immunotherapy. We assessed the value of CRGS in predicting the prognosis of HCC patients in the TCGA cohort and validated whether CRGS could be used to predict the prognosis of HCC patients in the ICGC dataset. To explore the role of CRGS in predicting immunotherapy response and drug sensitivity in HCC patients based on data from the TCGA cohort, and to apply the Migort210 immunotherapy cohort to validate the clinical value of CRGS in predicting immunotherapy in malignant tumors. Results:CRGS consists of four copper death-related genes: GLS, CDKN2A, LIPT1, and DLAT. Patients in the high-risk group TCGA had lower overall survival (OS), disease-specifical survival, and progression-free interval than those in the low-risk group TCGA (all P<0.01). OS of patients in the high-risk group ICGC was lower than that in the low-risk group ICGC ( P=0.022). Multivariate Cox regression analysis showed that CRGS was an independent risk factor for poor prognosis in HCC patients (TCGA: HR=2.991, 95% CI: 1.781-5.049, P<0.001; ICGC: HR=4.621, 95% CI: 1.685-12.674, P=0.033). Risk scores were positively correlated with the expression levels of CTLA4, PDCD1, CD80 and HLLA2 (all P<0.001). Patients in the high-risk group TCGA had lower tumor immune dysfunction and rejection scores than those in the low-risk group TCGA [-0.04(-0.07, -0.02) vs. -0.02(-0.04, 0) points], and the difference was statistically significant ( P<0.001). Patients in the responder group had a higher risk score than the non-responder group [1.70 (1.56, 1.90) vs. 1.63 (1.52, 1.80)], with a statistically significant difference ( P<0.05). The half-inhibitory concentrations (IC 50) for sunitinib, rapamycin and etanercept were higher in the high-risk group TCGA than that in the low-risk group TCGA, while the IC 50 for erlotinib was lower than that in the low-risk group TCGA, and the differences were all statistically significant (all P<0.001). Conclusion:The CRGS might be served as a potential biomarker to predict the prognoses, immunotherapy response, and drug sensitivity of patients with HCC.

Objective:To evaluate the relationship between mitochondrial calcium uniporter protein (MCU)-mediated mitochondrial dynamics and intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four wild-type adult male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (IIR group), sham operation+ MCU inhibitor Ru360 group (S+ Ru360 group) and intestinal I/R + Ru360 group (IIR+ Ru360 group). The mouse model of intestinal I/R injury was prepared by clamping the root of the superior mesenteric artery for 45 min followed by 2 h of reperfusion in anesthetized animals. Small intestinal tissues were obtained at the end of reperfusion for examination of the intestinal mucosal injury which was scored according to Chiu and for determination of the content of malondialdehyde (MDA) (TBA method), activity of superoxide dismutase (SOD) (WST-8 method), content of lactic dehydrogenase (LDH) (colorimetric method), and expression of MCU, dynamin-related protein 1 (Drp1), recombinant human mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1) and Mfn2 (by Western blot). Results:Compared with S and S+ Ru360 groups, the Chiu′s score and contents of MDA and LDH were significantly increased, the activity of SOD was decreased, the expression of MCU, Drp1 and Fis1 was up-regulated, and the expression of Mfn1 and Mfn2 was down-regulated in IIR and IIR+ Ru360 groups ( P<0.05). Compared with IIR group, the Chiu′s score and contents of MDA and LDH were significantly decreased, the activity of SOD was increased, the expression of MCU, Drp1 and Fis1 was down-regulated, and the expression of Mfn1 and Mfn2 was up-regulated in IIR+ Ru360 group ( P<0.05). Conclusions:The mechanism underlying intestinal I/R injury may be related to MCU-induced promotion of mitochondrial fission, reduction of mitochondrial fusion and mediation of imbalance in mitochondrial dynamics in mice.

Objective:To investigate the application effect of scenario infiltration combined with interactive teaching in the teaching of nursing interns in the department of infectious diseases.Methods:A total of 120 nursing students who received training in Department of Infectious Diseases, Beijing Luhe Hospital Affiliated to Capital Medical University, were selected as subjects; 58 nursing students who received routine teaching were enrolled as conventional teaching group, and 62 nursing students who received scenario infiltration combined with interactive teaching were enrolled as combined teaching group. The two groups were compared in terms of self-evaluation teaching effect, nurse-patient communication ability, assessment scores, awareness of protection, and teaching satisfaction. SPSS 22.0 was used for the t-test and the chi-square test. Results:After the end of internship, compared with the conventional teaching group, the combined teaching group had significantly higher self-evaluation scores of learning interest, thinking ability, operational skills, teamwork awareness, and problem-solving ability ( P<0.05), significantly higher scores of planning and preparing, initiating communication, collecting and providing information, obtaining and understanding patient perspectives, and ending communication ( P<0.05), and significantly higher assessment scores of theoretical knowledge, nursing operational skills, and emergency and rescue abilities ( P<0.05). Compared with the conventional teaching group, the combined teaching group had a significantly higher proportion of nursing students who correctly disposed medical waste (96.77% vs. 79.31%) and a significantly lower proportion of nursing students with insufficient self-protection ability (4.84% vs. 22.41%). Compared with the conventional teaching group, the combined teaching group had significantly higher satisfaction scores of teaching content, course design, and teaching effect ( P<0.05). Conclusion:The application of scenario infiltration combined with interactive teaching can better meet the teaching needs of nursing interns in the department of infectious diseases and effectively improve their communication skills, comprehensive abilities, and awareness of protection, and therefore, it holds promise for further application.

Objective:To evaluate the role of autophagy in ischemia postconditioning (IPO)-induced attenuation of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 9-12 weeks, weighing 25-29 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (group S), intestinal I/R group (group IIR), group IPO and IPO plus 3-methyladenine (3-MA) group (group IPO+ 3-MA). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.The mice underwent 3 cycles of 30-s reperfusion followed by 30-s ischemia before restoration of reperfusion in group IPO.Blood samples from the femoral artery were collected at 2 h of reperfusion for determination of concentrations of serum diamine oxidase (DAO), D-lactate (D-LA) and intestinal fatty acid binding protein (I-FABP). The animals were then sacrificed and intestinal tissues were removed for microscopic examination of the pathologic changes which were scored according to Chiu and for determination of the expression of autophagy-related proteins Beclin-1 and p62 (by Western blot). The water content of intestinal tissues was calculated. Results:Compared with group S, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly increased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in IIR, IPO and IPO+ 3-MA groups ( P<0.05). Compared with group IIR, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly decreased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in group IPO ( P<0.05). Compared with group IPO, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, and water content of intestinal tissues were significantly increased, LC3Ⅱ/LC3Ⅰratio was decreased, Beclin-1 expression was down-regulated, and p62 expression was up-regulated in group IPO+ 3-MA ( P<0.05). Conclusion:Autophagy is involved in ischemia postconditioning-induced attenuation of intestinal I/R injury in mice.

Objective To evaluate the effect of anti-myosin monoclonal antibodies-nuclear factor kappa B (NF-κB) decoy oligodeoxynucleotides-lipofectamine compound (mAb2G4-ODN-lip) on myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty clean-grade healthy adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 240-260 g,were divided into 4 groups (n=10 each) using a random number table:sham operation group (group S),myocardial I/R group (group I/R),ODN-lip group (group ODN) and mAb2G4-ODN-lip group (group mAb2G4).Myocardial I/R was induced by occlusion of the left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion.In ODN and mAb2G4 groups,ODN-lip (100 μg ODN) and mAb2G4-ODN-lip (100 μg ODN) compounds were injected via the femoral vein,respectively,immediately after onset of ischemia.The left anterior descending branch of coronary artery was only occluded but not ligated in group S.The animals were sacrificed at 120 min of reperfusion and myocardial specimens of the left ventricle on the ischemic side were obtained for examination of the pathological changes (using haematoxylin and eosin staining) and for determination of the expression of NF-κB (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay).Results Compared with group S,the expression of NF-κB was significantly up-regulated,and the contents of TNF-α and IL-6 were increased in I/R,ODN and mAb2G4 groups (P＜ 0.05).Compared with group I/R,the expression of NF-κB was significantly down-regulated,and the contents of TNF-α and IL-6 were decreased in ODN and mAb2G4 groups (P＜0.05).Compared with group ODN,the expression of NF-κB was significantly down-regulated,and the contents of TNF-α and IL-6 were decreased in group mAb2G4 (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group I/R,group ODN and group mAb2G4 in turn.Conclusion mAb2G4-ODN-lip can mitigate myocardial I/R injury in rats.

Objective To evaluate the effect of oxycodone preconditioning on mitochondrion-dependent apoptosis in liver ceils during intestinal ischemia-reperfusion (I/R) in rats.Methods Fifty-four healthy male Sprague-Dawley rats,weighing 200-300 g,were divided into 9 groups (n=6 each) using a random number table:sham operation group (group S),I/R group,oxycodone preconditioning group (group OP),μ receptor blocker CTOP group (group CTOP),δ receptor blocker naltrindole (NTD) group (group NTD),κ receptor blocker nor-binaltorphimne (BNI) group (group BNI),CTOP plus oxycodone preconditioning group (group CTOP+OP),NTD plus oxycodone preconditioning group (group NTD+ OP),and BN1 plus oxycodone preconditioning group (group BNI+OP).The model of intestinal I/R was established by occluding the superior mesenteric artery for 45 min followed by 2 h reperfusion.Oxycodone 0.5 mg/kg was injected intravenously at 10 min prior to ischemia in OP,COTP+OP,NTD+OP and BNI+ OP groups.COTP 1 mg/kg and NTD 5 mg/kg were injected intravenously at 20 min prior to ischemia in COTP+OP and NTD+OP groups,respectively.BNI 5 mg/kg was injected intravenously at 25 min prior to ischemia in group BNI+OP.CTOP 1 mg/kg and NTD 5 mg/kg were injected intravenously at 10 min prior to ischemia in CTOP and NTD groups,respectively.BNI 5 mg/kg was injected intravenously at 15 min prior to ischemia in group BNI.The superior mesenteric artery was only exposed but not occluded in group S.The rats were sacrificed at 2 h of reperfusion,and livers were removed for determination of apoptosis in liver cells (using TUNEL) and expression of Bcl-2 and caspase-3 in liver tissues (by immunohistochemistry).The apoptosis index (AI) was calculated.Results Compared with group S,AI was significantly increased,the expression of Bcl-2 was down-regulated and the expression of caspase-3 was up-regulated in the other eight groups (P＜0.05).Compared with group I/R,AI was significantly decreased,the expression of Bcl-2 was up-regulated,and the expression of caspase-3 was down-regulated in group OP (P＜0.05).Compared with group OP,AI was significantly increased,Bcl-2 expression was down-regulated,and caspase-3 expression was up-regulated in COTP+OP,NTD+OP and BNI+OP groups (P＜0.05).Conclusion The mechanism by which oxycodone preconditioning activates μ,δ and κ receptors and reduces intestinal I/R injury may be related to inhibiting mitochondrion-dependent apoptosis in rats.