Objective:To explore the mechanisms of oxaliplatin resistance mediated by TET2 methylation in the treatment of acute lymphoblastic leukemia (ALL) using bioinformatics methods.Methods:The data on drug-resistant and sensitive cell lines related to oxaliplatin treatment for ALL were download using the Genomics of Drug Sensitivity in Cancer (GDSC) database (updated in December 2023); the drug-resistant cell lines were screened based on half maximal inhibitory concentration ( IC50) > 10 μmol/L, and the difference in IC50 between drug-resistant and sensitive cell lines were analyzed using Mann-Whitney U test. The cancer driver mutation genes in drug-resistant cell lines were retrieved using the Cancer Cell Line Encyclopedia (CCLE) database (updated in December 2023). Using the protein-protein interaction (PPI) network functional enrichment analysis (STRING) database (updated in June 2024), PPI network analysis was performed on cancer driver mutation genes with biological functions. A confidence threshold of ≥ 0.7 (high confidence) and an average network node degree above 4 (high average) were selected to screen for cancer driver mutation genes with significant biological functions. Using the microRNA Data Integration Portal (mirDIP) database (updated in June 2024), the coexpression data of microRNA (miRNA) and mutant target genes were queried, miRNA-target gene pairs were screened according to the highest score threshold of 1% miRNA and interaction score > 0.9, and the regulatory effect of miRNA on mutant genes was analyzed. DNA methylation data were download from the Methylation in Human Cancer (MethHC) database (updated in June 2024) and the methylSig R software package was used to analyze the differentially methylated regions (DMR) of DNA methylation between drug-resistant and sensitive cell lines; genes with P < 0.05 and absolute difference > 0.2 were selected, and they were divided into high methylation gene group and low methylation gene group. Spearman correlation analysis and Spearman rank test were performed for the degree of methylation and gene expression, and the key genes with P < 0.01 were screened to reveal the relationship between methylation degree and gene expression. Results:As a result of searching the GDSC database, there were a total of 9 drug-resistant cell lines and 17 sensitive cell lines related to oxaliplatin treatment for ALL; after Z-score normalization of IC50 data between drug-resistant and sensitive cell lines, the average rank of drug-resistant cell lines was 21, and the average rank of sensitive cell lines was 8.5, with a statistically significant difference ( Z = -4.08, P < 0.01). Eight cancer driver mutation genes with significant biological functions that lead to drug resistance of the cell lines were screened using the CCLE database and STRING database. According to the mirDIP database, there were a total of 12 pairs of miRNA-target gene pairs with miRNA-target gene interaction scores >0.9. miRNA had strong regulatory effects on the expressions of NRAS and MAP2K1 target genes. In the MethHC database, the β values (numerical value of increased methylation level) of DMR for genes such as TP53, RXRG and SGIP in drug-resistant cell lines were 0.151, 0.165 and 0.149, respectively, compared to those in sensitive cell lines, the differences were statistically significant (all P < 0.01). The degree of methylation of SGIP gene was negatively correlated with the relative expression level of SGIP mRNA ( r = -0.71, P < 0.01), and SGIP gene underwent high methylation at promoter site 143886940. The cg08321569 locus in the TET2 gene domain of drug-resistant cell lines exhibited persistent high methylation, with a methylation level of β = 0.89. This locus was located 1.2 kb downstream of the transcription start point of exon 4, and the degree of TET2 methylation was negatively correlated with the relative expression level of TET2b mRNA ( r = -0.81, P < 0.01). Conclusions:TET2 methylation may be an important factor for oxaliplatin resistance in the treatment of ALL.

Objective To investigate mitochondrial function mediated by phospholipase D1(PLD1)in the lungs of mice with bronchopulmonary dysplasia.Methods Wild-type(WT)and PLD1 knockout(PLD1-KO)newborn mice were assigned to four groups:normoxic+WT,normoxic+PLD1-KO,hyperoxic+WT,and hyperoxic+PLD1-KO,with nine mice in each group.Mice in the hyperoxia groups were exposed to hyperoxia(85％ O2)for 14 days.Mice in the normoxic groups were exposed to normoxic conditions(21％ O2)for 14 days.On the 14th day,the levels of oxidative stress,apoptosis,and fibrosis in lungs were evaluated using commercial kits for malondialdehyde(MDA)and superoxide dismutase(SOD),Western blot for BAX,BCL-2,and Cleaved Caspase-3,and immunohistochemistry for α-SMA and AIF.The following MLE-12 cell groups were prepared,normoxic+si-NC,hyperoxic+si-NC,normoxic+si-PLD1,and hyperoxic+si-PLD1.After transient transfection,the cells were exposed to normoxia or hyperoxia for 24 h.Mitochondrial reactive oxygen species(mtROS)and function were measured using MitoSOX Red and the hippocampus mitochondrial stress test.Results The levels of α-SMA and AIF staining,MDA,Cleaved Caspase 3,and BAX in lung tissue were significantly increased in the hyperoxic groups compared with the normoxic groups(P＜0.05),while SOD activity and BCL-2 levels were significantly decreased(P＜0.05).α-SMA and AIF staining,and the abundance of Cleaved Caspase-3 and BAX in lung tissue were lower in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05),while SOD activity and BCL-2 abundance were higher in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic groups was significantly lower than that in the normoxic groups(P＜0.05);however,the level of AIF was increased significantly in the cytoplasm of the hyperoxic groups compared with the normoxic groups(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic+si-PLD1 group was significantly increased compared with that in the hyperoxic+si-NC group(P＜0.05).The abundance of mtROS in hyperoxia MLE-12 cell groups was higher than that in the normoxia groups(P＜0.05),and the abundance of mtROS in the hyperoxia+si-PLD1 group was lower than that in the hyperoxia+si-NC group(P＜0.05).Compared with the normoxic+si-NC group,basic respiration,ATP production,maximum respiration,and spare respiratory capacity was significantly decreased in the hyperoxic+si-NC group(P＜0.05).Compared with the hyperoxic+si-NC group,the hyperoxic+si-PLD1 group had significantly increased basic respiration,ATP production,maximum respiration,and spare respiratory capacity(P＜0.05).Conclusions PLD1 is involved in hyperoxia-induced injury of mouse BPD and MLE-12 cells.Deletion of the PLD1 gene may alleviate hyperoxia-induced lung injury by inhibiting mitochondrial-dependent apoptosis.

Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Objective:To explore the mechanisms of oxaliplatin resistance mediated by TET2 methylation in the treatment of acute lymphoblastic leukemia (ALL) using bioinformatics methods.Methods:The data on drug-resistant and sensitive cell lines related to oxaliplatin treatment for ALL were download using the Genomics of Drug Sensitivity in Cancer (GDSC) database (updated in December 2023); the drug-resistant cell lines were screened based on half maximal inhibitory concentration ( IC50) > 10 μmol/L, and the difference in IC50 between drug-resistant and sensitive cell lines were analyzed using Mann-Whitney U test. The cancer driver mutation genes in drug-resistant cell lines were retrieved using the Cancer Cell Line Encyclopedia (CCLE) database (updated in December 2023). Using the protein-protein interaction (PPI) network functional enrichment analysis (STRING) database (updated in June 2024), PPI network analysis was performed on cancer driver mutation genes with biological functions. A confidence threshold of ≥ 0.7 (high confidence) and an average network node degree above 4 (high average) were selected to screen for cancer driver mutation genes with significant biological functions. Using the microRNA Data Integration Portal (mirDIP) database (updated in June 2024), the coexpression data of microRNA (miRNA) and mutant target genes were queried, miRNA-target gene pairs were screened according to the highest score threshold of 1% miRNA and interaction score > 0.9, and the regulatory effect of miRNA on mutant genes was analyzed. DNA methylation data were download from the Methylation in Human Cancer (MethHC) database (updated in June 2024) and the methylSig R software package was used to analyze the differentially methylated regions (DMR) of DNA methylation between drug-resistant and sensitive cell lines; genes with P < 0.05 and absolute difference > 0.2 were selected, and they were divided into high methylation gene group and low methylation gene group. Spearman correlation analysis and Spearman rank test were performed for the degree of methylation and gene expression, and the key genes with P < 0.01 were screened to reveal the relationship between methylation degree and gene expression. Results:As a result of searching the GDSC database, there were a total of 9 drug-resistant cell lines and 17 sensitive cell lines related to oxaliplatin treatment for ALL; after Z-score normalization of IC50 data between drug-resistant and sensitive cell lines, the average rank of drug-resistant cell lines was 21, and the average rank of sensitive cell lines was 8.5, with a statistically significant difference ( Z = -4.08, P < 0.01). Eight cancer driver mutation genes with significant biological functions that lead to drug resistance of the cell lines were screened using the CCLE database and STRING database. According to the mirDIP database, there were a total of 12 pairs of miRNA-target gene pairs with miRNA-target gene interaction scores >0.9. miRNA had strong regulatory effects on the expressions of NRAS and MAP2K1 target genes. In the MethHC database, the β values (numerical value of increased methylation level) of DMR for genes such as TP53, RXRG and SGIP in drug-resistant cell lines were 0.151, 0.165 and 0.149, respectively, compared to those in sensitive cell lines, the differences were statistically significant (all P < 0.01). The degree of methylation of SGIP gene was negatively correlated with the relative expression level of SGIP mRNA ( r = -0.71, P < 0.01), and SGIP gene underwent high methylation at promoter site 143886940. The cg08321569 locus in the TET2 gene domain of drug-resistant cell lines exhibited persistent high methylation, with a methylation level of β = 0.89. This locus was located 1.2 kb downstream of the transcription start point of exon 4, and the degree of TET2 methylation was negatively correlated with the relative expression level of TET2b mRNA ( r = -0.81, P < 0.01). Conclusions:TET2 methylation may be an important factor for oxaliplatin resistance in the treatment of ALL.

ObjectiveTo assess the level of health literacy and its influencing factors among middle school students aged 12‒18 years in Jing’an District, Shanghai, so as to provide a solid scientific foundation for further developing more targeted intervention measures. MethodsA stratified cluster random sampling method was used to randomly select 4 middle schools in Jing’an District, Shanghai from November to December 2023, and conducted a health literacy questionnaire survey on non-graduating middle and high school students, respectively. The2023 Survey on the Status of Health Literacy among Middle School Students in Jing’an District, Shanghai was adopted, which consisted of two parts: health literacy and basic information. Health literacy was divided into three dimensions: health knowledge and concept literacy, healthy lifestyle and behavior literacy, and health skill literacy. Three dimensions could be categorized into six types of health literacy issue: scientific health literacy, infectious disease prevention and control literacy, chronic disease prevention and control literacy, safety and first aid literacy, basic health literacy, and health information literacy. ResultsA total of 1 161 middle school students were enrolled into this study, including 571 males and 570 females. The overall health literacy level of middle school students was 33.51%, with 34.81% among middle school students and 31.69% among high school students, respectively. Results of logistic regression analysis showed that health knowledge acquisition and awareness, as well as application frequency of health knowledge, were the influencing factors for the overall health literacy level among middle school students (P<0.05). The degree of family attention to health maintenance, health knowledge acquisition and awareness, and application frequency of health knowledge were the main influencing factors for the three dimensions and literacy of six types of health issues among middle school students (P<0.05). ConclusionThe levels of different types of health literacy among middle school students in Jing’an District are uneven, with the highest being safety and first aid literacy and the lowest being basic health literacy. It is recommended to take targeted measures to comprehensively improve the health literacy level of middle school students.

Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Objective To investigate mitochondrial function mediated by phospholipase D1(PLD1)in the lungs of mice with bronchopulmonary dysplasia.Methods Wild-type(WT)and PLD1 knockout(PLD1-KO)newborn mice were assigned to four groups:normoxic+WT,normoxic+PLD1-KO,hyperoxic+WT,and hyperoxic+PLD1-KO,with nine mice in each group.Mice in the hyperoxia groups were exposed to hyperoxia(85％ O2)for 14 days.Mice in the normoxic groups were exposed to normoxic conditions(21％ O2)for 14 days.On the 14th day,the levels of oxidative stress,apoptosis,and fibrosis in lungs were evaluated using commercial kits for malondialdehyde(MDA)and superoxide dismutase(SOD),Western blot for BAX,BCL-2,and Cleaved Caspase-3,and immunohistochemistry for α-SMA and AIF.The following MLE-12 cell groups were prepared,normoxic+si-NC,hyperoxic+si-NC,normoxic+si-PLD1,and hyperoxic+si-PLD1.After transient transfection,the cells were exposed to normoxia or hyperoxia for 24 h.Mitochondrial reactive oxygen species(mtROS)and function were measured using MitoSOX Red and the hippocampus mitochondrial stress test.Results The levels of α-SMA and AIF staining,MDA,Cleaved Caspase 3,and BAX in lung tissue were significantly increased in the hyperoxic groups compared with the normoxic groups(P＜0.05),while SOD activity and BCL-2 levels were significantly decreased(P＜0.05).α-SMA and AIF staining,and the abundance of Cleaved Caspase-3 and BAX in lung tissue were lower in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05),while SOD activity and BCL-2 abundance were higher in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic groups was significantly lower than that in the normoxic groups(P＜0.05);however,the level of AIF was increased significantly in the cytoplasm of the hyperoxic groups compared with the normoxic groups(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic+si-PLD1 group was significantly increased compared with that in the hyperoxic+si-NC group(P＜0.05).The abundance of mtROS in hyperoxia MLE-12 cell groups was higher than that in the normoxia groups(P＜0.05),and the abundance of mtROS in the hyperoxia+si-PLD1 group was lower than that in the hyperoxia+si-NC group(P＜0.05).Compared with the normoxic+si-NC group,basic respiration,ATP production,maximum respiration,and spare respiratory capacity was significantly decreased in the hyperoxic+si-NC group(P＜0.05).Compared with the hyperoxic+si-NC group,the hyperoxic+si-PLD1 group had significantly increased basic respiration,ATP production,maximum respiration,and spare respiratory capacity(P＜0.05).Conclusions PLD1 is involved in hyperoxia-induced injury of mouse BPD and MLE-12 cells.Deletion of the PLD1 gene may alleviate hyperoxia-induced lung injury by inhibiting mitochondrial-dependent apoptosis.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Purpose/Significance The internet consultation user portrait is constructed to explore the consultation topic,improve the consultation service quality,reduce the communication barriers between doctors and patients,and provide targeted treatment in an online and offline manner.Method/Process Python crawler is used to obtain the autism diagnosis data of a medical platform,and the combined model of LDA and TF-TFIDF is used to divide the data,and the user group classification is realized after dimensionality reduction clus-tering.Finally,the characteristic sets of different user groups are calculated and output by logistic regression model to construct the por-trait.Result/Conclusion The consultation content of users mainly focuses on 11 topics.The platform can optimize the consultation filling template based on the typical characteristics of the subject content to improve the accuracy of the disease description,consultation effi-ciency and satisfaction of patients.

Antineoplastic drugs refer to the drugs that act at the cellular and molecular levels to inhibit tumor growth or eliminate tumors through pathways such as cell killing,immune regulation,and endocrine regulation.Antineoplastic drugs generally including chemotherapeutic drugs,molecular targeted therapeutic drugs,immunotherapeutic drugs,and endocrine therapeutic drugs.The management and rational application of antineoplastic drugs in medical institutions are related to the safety of patient treatment.The standard for management of antineoplastic drugs use in clinical is compiled by the Pharmaceutical Affairs Committee of China Hospital Association,which specification requirements 18 key elements in the organizational management and system,medication management,drug monitoring and evaluation of antineoplastic drug management in healthcare institutions.This standard is applicable to all levels and types of healthcare institutions carrying out oncology diagnosis and treatment.This paper describes the methodology and basic content of the standard,hoping to providing a reference for medical institutions to carry out relevant work.