The dual induction therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has resulted in a cure rate exceeding 90% for patients with acute promyelocytic leukemia (APL). However, relapse due to ATO resistance remains a pressing clinical challenge. This article reviews recent research progress of PML mutations, metabolic adaptation, ATO metabolism, miRNA, snoRNA, the pathogenic mechanisms of the PML::RARA fusion protein and resistance mechanisms of autophagy. Additionally, the paper also discusses the clinical application of new treatment strategies such as venetoclax and gemtuzumab ozogamicin based on the drug-resistance mechanisms.

Objective:To evaluate the role of myosin heavy chain 9(MYH9) in gut-vascular barrier damage in septic mice.Methods:Eighty SPF C57BL/6J male mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups( n=20 each) by the random number table method: sham operation group(Sham group), sham operation + MYH9 inhibitor blebbistatin group(Sham+ Ble group), cecal ligation and perforation(CLP) group, and CLP+ blebbistatin group(CLP+ Ble group). A mouse sepsis model was established using CLP in anesthetized animals. Blebbistatin solution 5 mg/kg was intraperitoneally injected at 1 h before CLP in Sham+ Ble and CLP+ Ble groups, while the equal volume of phosphate buffer was given instead in Sham and CLP groups. Fourteen mice were randomly selected from each group to observe the survival at 24 h after CLP. Blood samples were taken by apical puncture at 24 h after surgery in the remaining 6 mice in each group for determination of the plasma concentrations of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6)(using enzyme-linked immunosorbent assay), expression of plasma membrane vesicle-associated protein(PLVAP) in intestinal microvascular endothelial cells(using immunofluorescence), and expression of MYH9, PLVAP, vascular endothelial calreticulin(VE-cadherin) and β-catenin protein and mRNA(by Western bot or fluorescent quantitative real-time polymerase chain reaction) and for examination of the pathological changes of intestinal tissues. Intestinal damage was assessed and scored according to Chiu. Results:Compared with Sham group, the expression of MYH9 protein and mRNA was significantly down-regulated in Sham+ Ble group, and the survival rate was significantly decreased at 24 h after surgery, Chiu′s scores in intestinal tissues were increased, the plasma concentrations of TNF-α, IL-1β and IL-6 were increased, the expression of PLVAP in intestinal microvascular endothelial cells was up-regulated, the expression of MYH9 and PLVAP protein and mRNA in intestinal tissues was up-regulated, and the expression of VE-cadherin and β-catenin protein and mRNA was down-regulated in CLP group( P<0.05). Compared with CLP group, the survival rate was significantly increased at 24 h after surgery, Chiu′s scores in intestinal tissues were decreased, the plasma concentrations of TNF-α, IL-1β and IL-6 were decreased, the expression of PLVAP in intestinal microvascular endothelial cells was down-regulated, the expression of MYH9 and PLVAP protein and mRNA in intestinal tissues was down-regulated, and the expression of VE-cadherin and β-catenin protein and mRNA was up-regulated in CLP+ Ble group( P<0.05). Conclusions:MYH9 is involved in gut-vascular barrier damage in septic mice.

Objective:To evaluate the role of mitochondrial fusion protein 2 (Mfn2)-mediated mitochondrial homeostasis in hypoxia-reoxygenation injury in human colorectal adenocarcinoma cells.Methods:Human colorectal adenocarcinoma cell line Caco-2 was cultured in vitro and divided into 4 groups ( n=30 each) using a random number table method: control group (C group), hypoxia-reoxygenation group (HR group), transfection with negative control virus plus hypoxia-reoxygenation group (Vector+ HR group) and transfection with Mfn2 plus hypoxia-reoxygenation group (Mfn2+ HR group). Mfn2 was packaged by lentivirus and transfected into Caco-2 cells, and the hypoxia-reoxygenation model was established through exposing cells to hypoxia for 12 h followed by 2 h reoxygenation. The cell viability and levels of lactate dehydrogenase (LDH) were measured. The expression of Mfn2, Occludin, Claudin-1, E-cadherin and microtubule-associated protein 1 light chain 3 Ⅰ (LC3Ⅰ), LC3Ⅱ, P62, translocase of outer mitochondrial membrane (TOM20) and cytochrome c oxidase Ⅳ (COX Ⅳ) was detected by Western blot. The levels of ATP content and ROS were determined. Results:Compared with C group, the cell viability and ATP content were significantly decreased, the LDH activity and ROS level were increased, the expression of Mfn2, Occludin, Claudin-1 and E-cadherin was down-regulated, the expression of LC3Ⅱ was up-regulated, and the expression of P62, TOM20 and COX Ⅳ was down-regulated in HR group ( P<0.05). Compared with HR group, the cell viability and ATP content were significantly increased, the LDH activity and ROS level were decreased, the expression of Mfn2, Occludin, Claudin-1 and E-cadherin was up-regulated, the expression of LC3Ⅱ was down-regulated, and the expression of P62, TOM20 and COX Ⅳ was up-regulated in Mfn2+ HR group ( P<0.05), and no significant change was found in the aforementioned parameters in Vector+ HR group ( P>0.05). Conclusions:Mfn2 may alleviate hypoxia-reoxygenation injury in human colorectal adenocarcinoma cells by maintaining mitochondrial homeostasis.

Objective:To evaluate the role of myosin heavy chain 9(MYH9) in gut-vascular barrier damage in septic mice.Methods:Eighty SPF C57BL/6J male mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups( n=20 each) by the random number table method: sham operation group(Sham group), sham operation + MYH9 inhibitor blebbistatin group(Sham+ Ble group), cecal ligation and perforation(CLP) group, and CLP+ blebbistatin group(CLP+ Ble group). A mouse sepsis model was established using CLP in anesthetized animals. Blebbistatin solution 5 mg/kg was intraperitoneally injected at 1 h before CLP in Sham+ Ble and CLP+ Ble groups, while the equal volume of phosphate buffer was given instead in Sham and CLP groups. Fourteen mice were randomly selected from each group to observe the survival at 24 h after CLP. Blood samples were taken by apical puncture at 24 h after surgery in the remaining 6 mice in each group for determination of the plasma concentrations of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6)(using enzyme-linked immunosorbent assay), expression of plasma membrane vesicle-associated protein(PLVAP) in intestinal microvascular endothelial cells(using immunofluorescence), and expression of MYH9, PLVAP, vascular endothelial calreticulin(VE-cadherin) and β-catenin protein and mRNA(by Western bot or fluorescent quantitative real-time polymerase chain reaction) and for examination of the pathological changes of intestinal tissues. Intestinal damage was assessed and scored according to Chiu. Results:Compared with Sham group, the expression of MYH9 protein and mRNA was significantly down-regulated in Sham+ Ble group, and the survival rate was significantly decreased at 24 h after surgery, Chiu′s scores in intestinal tissues were increased, the plasma concentrations of TNF-α, IL-1β and IL-6 were increased, the expression of PLVAP in intestinal microvascular endothelial cells was up-regulated, the expression of MYH9 and PLVAP protein and mRNA in intestinal tissues was up-regulated, and the expression of VE-cadherin and β-catenin protein and mRNA was down-regulated in CLP group( P<0.05). Compared with CLP group, the survival rate was significantly increased at 24 h after surgery, Chiu′s scores in intestinal tissues were decreased, the plasma concentrations of TNF-α, IL-1β and IL-6 were decreased, the expression of PLVAP in intestinal microvascular endothelial cells was down-regulated, the expression of MYH9 and PLVAP protein and mRNA in intestinal tissues was down-regulated, and the expression of VE-cadherin and β-catenin protein and mRNA was up-regulated in CLP+ Ble group( P<0.05). Conclusions:MYH9 is involved in gut-vascular barrier damage in septic mice.

Objective:To evaluate the role of mitochondrial fusion protein 2 (Mfn2)-mediated mitochondrial homeostasis in hypoxia-reoxygenation injury in human colorectal adenocarcinoma cells.Methods:Human colorectal adenocarcinoma cell line Caco-2 was cultured in vitro and divided into 4 groups ( n=30 each) using a random number table method: control group (C group), hypoxia-reoxygenation group (HR group), transfection with negative control virus plus hypoxia-reoxygenation group (Vector+ HR group) and transfection with Mfn2 plus hypoxia-reoxygenation group (Mfn2+ HR group). Mfn2 was packaged by lentivirus and transfected into Caco-2 cells, and the hypoxia-reoxygenation model was established through exposing cells to hypoxia for 12 h followed by 2 h reoxygenation. The cell viability and levels of lactate dehydrogenase (LDH) were measured. The expression of Mfn2, Occludin, Claudin-1, E-cadherin and microtubule-associated protein 1 light chain 3 Ⅰ (LC3Ⅰ), LC3Ⅱ, P62, translocase of outer mitochondrial membrane (TOM20) and cytochrome c oxidase Ⅳ (COX Ⅳ) was detected by Western blot. The levels of ATP content and ROS were determined. Results:Compared with C group, the cell viability and ATP content were significantly decreased, the LDH activity and ROS level were increased, the expression of Mfn2, Occludin, Claudin-1 and E-cadherin was down-regulated, the expression of LC3Ⅱ was up-regulated, and the expression of P62, TOM20 and COX Ⅳ was down-regulated in HR group ( P<0.05). Compared with HR group, the cell viability and ATP content were significantly increased, the LDH activity and ROS level were decreased, the expression of Mfn2, Occludin, Claudin-1 and E-cadherin was up-regulated, the expression of LC3Ⅱ was down-regulated, and the expression of P62, TOM20 and COX Ⅳ was up-regulated in Mfn2+ HR group ( P<0.05), and no significant change was found in the aforementioned parameters in Vector+ HR group ( P>0.05). Conclusions:Mfn2 may alleviate hypoxia-reoxygenation injury in human colorectal adenocarcinoma cells by maintaining mitochondrial homeostasis.

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 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 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.