Objective To establish an oxidative stress mouse model of atopic dermatitis (AD) by applying 2,4-dinitrofluorobenzene (DNFB) to the back and post-auricular skin of KM mice, and to evaluate the regulatory role of the RAGE-NLRP3 axis (receptor for advanced glycation end products-NOD-like receptor family, pyrin domain containing 3 axis) in AD-related oxidative stress, thereby providing a potential therapeutic target for AD treatment. Methods Twenty SPF-grade female KM mice were randomly divided into a control group (Control group) and an experimental group (DNFB group), with 10 mice in each group. Mice in the Control group were treated with an acetone-olive oil vehicle (acetone: olive oil = 3:1) on their back and post-auricular skin. Mice in the DNFB group were treated with 0.5% DNFB (prepared by adding 0.5 g DNFB per 100 mL of acetone-olive oil vehicle) on the same areas, once daily for 14 consecutive days. The severity of skin lesions was scored on days 2, 4, 6, 9, 12, and 14 of treatment. On day 14, scratching behavior and ear thickness were evaluated. Ear swelling was evaluated on the final day by measuring bilateral ear thickness three times with a vernier caliper; the three measurements were averaged. HE staining was used to observe morphological and structural changes of cells in the back skin tissues. The mRNA and protein expression levels of RAGE (receptor for advanced glycation end products) in skin tissues were detected by quantitative real-time PCR, Western blot, and immunohistochemical staining. The mRNA expression levels of oxidative stress-related molecules, including NLRP3 (NOD-like receptor family, pyrin domain containing 3), caspase-1 (cysteine-dependent aspartate-specific protease 1), and IL-1β (Interleukin-1β), were detected by quantitative real-time PCR. Results On day 14, the back skin lesion scores of the Control group and DNFB group were (0.20±0.42) and (9.93±1.30) (P<0.000 1), respectively. Scratching behavior scores were (5.00±2.05) and (49.26±8.49) episodes, respectively (P<0.000 1), and ear thicknesses were (213.00±11.87) μm and (765.93±140.47) μm (P<0.000 1), respectively. The DNFB group exhibited marked skin dryness, desquamation, and thickening. HE staining results showed that skin inflammation was obvious in the DNFB group, consistent with the pathological features of AD. Quantitative real-time PCR and Western blot results showed that compared with the Control group, the mRNA expression level of RAGE in skin tissues of the DNFB group was significantly increased (P<0.05), and the protein expression level of RAGE was also significantly increased (P<0.01). Immunohistochemical staining results showed that compared with the Control group, skin tissue sections of the DNFB group exhibited thickened stratum corneum and fibrotic proliferation of fibroblasts in the interstitium under microscopic observation, with a significant increase in RAGE protein expression in the skin tissues (P<0.01). Quantitative real-time PCR results showed that the mRNA expression levels of NLRP3, caspase-1, and IL-1β in skin tissues of the DNFB group were all significantly increased (P<0.01). Conclusion The AD mouse oxidative stress model has been successfully established by topical DNFB application. RAGE may promote the development of AD by regulating the NLRP3 inflammasome and IL-1β release, forming an oxidative-inflammatory cascade, suggesting that it could be a potential therapeutic target for AD.

Objective:To explore the effectiveness of interprofessional cooperative simulation in teaching emergency care for shock patients among intensive care unit (ICU) undergraduate nursing students.Methods:An interprofessional cooperative simulation-based teaching faculty team was established for ICU undergraduate nursing students, and a shock case library was developed. Using convenience sampling, 32 ICU undergraduate nursing students in 2022 were selected as the control group and received conventional simulation-based teaching, with students rotating through roles as nurses, standardized patients, doctors, and family members. In the experimental group, 34 ICU undergraduate nursing students in 2023 and 24 ICU clinical medicine interns were recruited to act as doctors for interprofessional cooperative simulation-based teaching. Each group was divided into subgroups, with each subgroup consisting of 4-5 nursing students. One group completed simulation-based training per month for a total of 8 sessions, with each session lasting 3 hours. The teaching adopted the on-site "tidal ward" in situ simulation, and the scenarios included patient history collection and health assessment, shock emergency care, nursing evaluation, and health education. The differences between the two groups of nursing students were compared in terms of ICU exit theoretical assessment score, objective structured clinical examination skill assessment score, and satisfaction with simulation-based teaching. SPSS 22.0 was used for independent samples t test and Mann-Whitney U test. Results:The experimental group achieved significantly higher scores in theoretical assessment (84.65±8.06), total score of satisfaction with simulation-based teaching (101.00±5.13), and clinical learning and multiprofessional team dimensions (47.32±3.35) compared to the control group ( P<0.001). The experimental group achieved higher scores in objective structured clinical examination skill assessment (81.40±7.22), guiding feedback and reflection (37.50±3.04), and judgmental thinking and clinical reasoning (16.00±2.03) compared to the control group, though the differences were not significant ( P=0.977, 0.668, and 0.636). Conclusions:Interprofessional cooperative simulation enhances the shock patient emergency care abilities and satisfaction with simulation-based teaching for undergraduate nursing students.

Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

Objective:To explore the effectiveness of interprofessional cooperative simulation in teaching emergency care for shock patients among intensive care unit (ICU) undergraduate nursing students.Methods:An interprofessional cooperative simulation-based teaching faculty team was established for ICU undergraduate nursing students, and a shock case library was developed. Using convenience sampling, 32 ICU undergraduate nursing students in 2022 were selected as the control group and received conventional simulation-based teaching, with students rotating through roles as nurses, standardized patients, doctors, and family members. In the experimental group, 34 ICU undergraduate nursing students in 2023 and 24 ICU clinical medicine interns were recruited to act as doctors for interprofessional cooperative simulation-based teaching. Each group was divided into subgroups, with each subgroup consisting of 4-5 nursing students. One group completed simulation-based training per month for a total of 8 sessions, with each session lasting 3 hours. The teaching adopted the on-site "tidal ward" in situ simulation, and the scenarios included patient history collection and health assessment, shock emergency care, nursing evaluation, and health education. The differences between the two groups of nursing students were compared in terms of ICU exit theoretical assessment score, objective structured clinical examination skill assessment score, and satisfaction with simulation-based teaching. SPSS 22.0 was used for independent samples t test and Mann-Whitney U test. Results:The experimental group achieved significantly higher scores in theoretical assessment (84.65±8.06), total score of satisfaction with simulation-based teaching (101.00±5.13), and clinical learning and multiprofessional team dimensions (47.32±3.35) compared to the control group ( P<0.001). The experimental group achieved higher scores in objective structured clinical examination skill assessment (81.40±7.22), guiding feedback and reflection (37.50±3.04), and judgmental thinking and clinical reasoning (16.00±2.03) compared to the control group, though the differences were not significant ( P=0.977, 0.668, and 0.636). Conclusions:Interprofessional cooperative simulation enhances the shock patient emergency care abilities and satisfaction with simulation-based teaching for undergraduate nursing students.

Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.

Objective:To conduct a thorough analysis of the clinical characteristics in patients with trisomy 8 syndrome and autoimmune diseases, and to provide a new perspective on the diagnosis and management of the fever of unknown origin (FUO).Methods:Patients who were admitted to Huashan Hospital, Fudan University between July 1st, 2021 and May 1st, 2024 for FUO and subsequently diagnosed with trisomy 8 syndrome with autoimmune diseases were included. In this retrospective cohort study, patients were divided into infection and non-infection group according to the etiological evidence, and the clinical characteristics and treatments were collected and compared between the two groups. Statistical analysis was performed using the Mann-Whitney U test. Results:Among the nine enrolled patients, one case was associated with Behet syndrome (BD) without myelodysplastic syndrome (MDS) and without co-occurring infection, eight cases were associated with MDS, among which six cases had both BD and MDS, one case had allergic pneumonia, and one case had rheumatoid arthritis. Six MDS cases had infections. The C-reactive protein (CRP) level in the infection group was significantly higher than that in the non-infection group(72.39(14.62, 132.70) mg/L vs 3.68(2.30, 10.09) mg/L; Z=1.00, P=0.048). There were no statistically significant differences in other inflammatory markers (such as white blood cell count, platelet count, erythrocyte sedimentation rate, ferritin, and neutrophil CD64 index) between the infection and non-infection groups (all P>0.05). In the infection group, one had bacterial infection, five had fungal infections, including two cases of disseminated aspergillosis, one case of mixed bacterial, fungal, and viral infections, one case of mucormycosis combined with Enterococcus faecalis infection, and one case of pulmonary aspergillosis combined with disseminated Mycobacterium abscessus infection. Among the nine patients, eight patients received immunosuppressive treatment centered on the glucocorticoids and (or) thalidomide, and all six infected patients received the above immunosuppressive treatment based on the anti-infection therapy. Eight of the nine cases were stable and followed up regularly, while one case died due to worsening of illness. Conclusions:Autoimmune diseases associated with trisomy 8 syndrome is rare. In addition to anti-infection treatment, glucocorticoids, thalidomide or other immunosuppressive drugs should be administrated to suppress the inflammatory response in patients with co-infection, and the disease could be well controlled.

Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.

Objective:To conduct a thorough analysis of the clinical characteristics in patients with trisomy 8 syndrome and autoimmune diseases, and to provide a new perspective on the diagnosis and management of the fever of unknown origin (FUO).Methods:Patients who were admitted to Huashan Hospital, Fudan University between July 1st, 2021 and May 1st, 2024 for FUO and subsequently diagnosed with trisomy 8 syndrome with autoimmune diseases were included. In this retrospective cohort study, patients were divided into infection and non-infection group according to the etiological evidence, and the clinical characteristics and treatments were collected and compared between the two groups. Statistical analysis was performed using the Mann-Whitney U test. Results:Among the nine enrolled patients, one case was associated with Behet syndrome (BD) without myelodysplastic syndrome (MDS) and without co-occurring infection, eight cases were associated with MDS, among which six cases had both BD and MDS, one case had allergic pneumonia, and one case had rheumatoid arthritis. Six MDS cases had infections. The C-reactive protein (CRP) level in the infection group was significantly higher than that in the non-infection group(72.39(14.62, 132.70) mg/L vs 3.68(2.30, 10.09) mg/L; Z=1.00, P=0.048). There were no statistically significant differences in other inflammatory markers (such as white blood cell count, platelet count, erythrocyte sedimentation rate, ferritin, and neutrophil CD64 index) between the infection and non-infection groups (all P>0.05). In the infection group, one had bacterial infection, five had fungal infections, including two cases of disseminated aspergillosis, one case of mixed bacterial, fungal, and viral infections, one case of mucormycosis combined with Enterococcus faecalis infection, and one case of pulmonary aspergillosis combined with disseminated Mycobacterium abscessus infection. Among the nine patients, eight patients received immunosuppressive treatment centered on the glucocorticoids and (or) thalidomide, and all six infected patients received the above immunosuppressive treatment based on the anti-infection therapy. Eight of the nine cases were stable and followed up regularly, while one case died due to worsening of illness. Conclusions:Autoimmune diseases associated with trisomy 8 syndrome is rare. In addition to anti-infection treatment, glucocorticoids, thalidomide or other immunosuppressive drugs should be administrated to suppress the inflammatory response in patients with co-infection, and the disease could be well controlled.

Objective: To establish the norm of the Physical Activity afterschool Questionnaire for Preschooler(P-PAQ) in urban areas of China, so as to provide a basis for graded guidance from the family perspective and to improve children s physical activity levels. Methods: From October 2020 to January 2021, 6 267 children aged 3-6 years old were recruited from 40 kindergartens in eight cities across six major administrative regions by stratified cluster sampling, and the P-PAQ initially developed by the researchers of this study were completed by the primary caregivers. The questionnaire was administered to collect data relating to the amount of physical activity undertaken by the preschoolers, and the norm was determined by quartiles. Data relating to parental concepts of sports and parental behavior were assessed by calculating mean scores in order to establish the norm. Results: Among preschoolers in urban areas, the M(P 25 ，P 75 ) of total physical activity time (min/day), moderate-to-vigorous physical activity time (min/day), outdoor time (min/day) and screen time (min/day) on school days outside kindergarten and on weekends were 84 (54,120), 22 (8,40), 12 (0,24) and 18 (6,30), and 170 (115,240), 60 (30,95), 90 (35,120) and 30 (20,60), respectively. When the score of parents sports concept and behavior (total score of 40) were≥34, 29-<34, 24-<29, <24, it was defined as four levels about above medium, medium, lower medium and lower, respectively. And for two dimensions，when the score of parental sports concept were ≥19, 17-<19, 15-<17, <15，and the score of parental behaviors were ≥16, 12-<16, 8-<12, <8, it was defined as four levels about upper medium, medium, lower medium and lower, respectively. Conclusion The norm of extracurricular activities among preschool children in Chinese cities has good representativeness and appropriate threshold values, which could provide a valuable reference for early assessment, as well as guidance in relation to out-of-school physical activity behaviors among children aged 3-6 years old.