Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5％imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.

Objective To analyze the deployment of policy instruments and the distribution of stakeholder engagement in provincial policies on nursing assistant training and management.Methods The relevant policy texts on nursing assistant training and management were systematically searched and collected from the official websites of provincial governments and their direct departments,CNKI,and the PKU Law Database.A two-dimensional framework of policy instruments-stakeholder was constructed,and the content analysis was used to classify,encode and quantify policy clauses.Results The study encompassed 20 provincial-level nursing assistant training and management policies,yielding a total of 359 codes.Within the policy instruments dimension,environmental,supply,and demand instruments constituted 66.30％,28.97％,and 4.74％,respectively.In terms of stakeholders,the management-side accounted for 56.55％,providers and trainers for 18.11％each,partners for 5.01％,and demand-side for 2.23％.Both management-side and trainers engaged with 3 policy instruments,providers with 2,and partners and demand-side with one each.Conclusion In the provincial nursing assistant training and management policies,there are differences in the deployment of policy instruments,and the distribution of stakeholders is uneven.Managers should pay attention to publicity guidance and platform construction,improve incentive mechanisms and training programs,and innovate cooperation models with stakeholders,as well as strengthen communication and exchange.

Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5％imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.

Objective:To investigate the role of alkylation repair homolog 5(ALKBH5)-mediated N6-methyladenosine(m6A)modifi-cation in endometrial decidualization.Methods:The mouse models of pregnancy and pseudopregnancy were established,and quantita-tive real-time PCR and Western blot were used to measure the expression pattern of ALKBH5 in the endometrium.The mouse and cell models of artificially induced decidualization were established,and quantitative real-time PCR,Western blot,and immunohistochemis-try were used to measure the expression levels of decidualization-related markers.The EpiQuik m6A RNA methylation quantification kit was used to measure the level of m6A.The mouse and cell models of artificially induced decidualization with interference of ALKBH5 expression were established,and quantitative real-time PCR,Western blot,and immunohistochemistry were used to measure the expression levels of decidualization-related markers,cell proliferation marker molecules,and apoptosis molecules.Flow cytometry was used to measure cell apoptosis rate.Results:In the mouse model of pregnancy,the expression level of ALKBH5 at the uterine em-bryo implantation site was significantly higher than that adjacent to the implantation site,and in the mouse and cell models of artifi-cially induced decidualization,compared with the control group,the induction group had a significant increase in the expression level of ALKBH5 and a significant reduction in the level of m6A.Inhibiting the expression of ALKBH5 led to an increase in the level of m6A,which in turn inhibited the proliferation of stromal cells,induced cell apoptosis,and ultimately impaired the normal process of en-dometrial decidualization.Conclusion:ALKBH5 deficiency leads to an increase in the level of m6A and decidualization injury in the en-dometrium,which lays a foundation for the research on m6A modifi-cation in decidualization.

This study analyzes the disease burden of Attention-Deficit Hyperactivity Disorder (ADHD) in children and adolescents in China and globally from 1990 to 2021, providing data support and strategic recommendations for public health policy and disease intervention.

BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Objective To analyze the deployment of policy instruments and the distribution of stakeholder engagement in provincial policies on nursing assistant training and management.Methods The relevant policy texts on nursing assistant training and management were systematically searched and collected from the official websites of provincial governments and their direct departments,CNKI,and the PKU Law Database.A two-dimensional framework of policy instruments-stakeholder was constructed,and the content analysis was used to classify,encode and quantify policy clauses.Results The study encompassed 20 provincial-level nursing assistant training and management policies,yielding a total of 359 codes.Within the policy instruments dimension,environmental,supply,and demand instruments constituted 66.30％,28.97％,and 4.74％,respectively.In terms of stakeholders,the management-side accounted for 56.55％,providers and trainers for 18.11％each,partners for 5.01％,and demand-side for 2.23％.Both management-side and trainers engaged with 3 policy instruments,providers with 2,and partners and demand-side with one each.Conclusion In the provincial nursing assistant training and management policies,there are differences in the deployment of policy instruments,and the distribution of stakeholders is uneven.Managers should pay attention to publicity guidance and platform construction,improve incentive mechanisms and training programs,and innovate cooperation models with stakeholders,as well as strengthen communication and exchange.

Background:The incidence of colorectal cancer(CRC)remains high in China.ITGBL1,an intergrin-like molecule,may play a significant role in the tumorigenesis and progression of CRC.Aims:To explore the expression of ITGBL1 in CRC tissues,and its clinical significance and effect on the biological function of CRC cells.Methods:Fifty-five paraffin embedding cancerous and paracancerous tissues from CRC patients undergoing surgical treatment were collected.Protein expression of ITGBL1 was detected by immunohistochemistry.The relationship between ITGBL1 expression and the clinicopathological characteristics of the CRC patients was analyzed.Furthermore,the sh-ITGBL1 lentiviral system was used to construct ITGBL1 knockdown stably-transformed HCT116 and RKO cells,then the ITGBL1 protein expression was detected by Western blotting.Effects of ITGBL1 knockdown on the proliferation of CRC cells were analyzed by CCK-8 assay and colony formation assay.Results:ITGBL1 was highly expressed in CRC tissues and cells.Expression of ITGBL1 was positively correlated with the infiltration depth,lymph node metastasis and the clinical stage of CRC(all P＜0.05),whereas no correlations were found between ITGBL expression and the gender,age,tumor size,tumor differentiation,and distant metastasis of CRC patients.Compared with the control group(sh-NC),ITGBL1 expression was significantly decreased in ITGBL1 knockdown(sh-ITGBL1)HCT116 and RKO cells,and the cell proliferation was significantly inhibited(all P＜0.05).Conclusions:Highly expressed ITGBL1 may be associated with the occurrence and development of CRC.ITGBL1 knockdown exerts a significant inhibitory effect on the proliferation of CRC cells.Therefore,ITGBL1 might be a potential biomarker,which is expected to be a new target for diagnosis and treatment of CRC.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

BACKGROUND:Our previous studies have confirmed that H2O2 and ginsenoside Rg1 can cause changes in reactive oxygen species levels in human periodontal ligament cells,but the correlation of reactive oxygen species with apoptosis and autophagy remains unclear. OBJECTIVE:To explore the effect and mechanism of ginsenoside Rg1 on H2O2-induced apoptosis and autophagy of human periodontal ligament cells. METHODS:Human periodontal ligament cells were divided into control group,H2O2 group and H2O2+Rg1 group.Ginsenoside Rg1(50 μmol/L)was pre-incubated for 24 hours and H2O2 was treated for 2 hours(500 μmol/L).CCK-8 assay was used to detect the proliferation ability of the cells.A fluorescent probe DCFH-DA was used to detect the reactive oxygen species level of the cells.qRT-PCR and western blot assay were used to detect heme oxygenase 1,apoptosis-related factor Caspase-3,Bax,anti-apoptotic factor Bcl-2,autophagy Beclin-1,P62,LC3,pathway-related factors phosphatidylinositol-3-kinase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR)mRNA and protein expression. RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation activity of human periodontal ligament cells in the H2O2 group decreased.Compared with the H2O2 group,the proliferation activity of human periodontal ligament cells increased in the H2O2+Rg1 group.(2)Compared with the control group,the expression of reactive oxygen species and heme oxygenase-1 increased in the H2O2 group.Compared with the H2O2 group,the expression of reactive oxygen species and heme oxygenase-1 decreased in the H2O2+Rg1 group.(3)Compared with the control group,the expression of Caspase-3,Bax,Beclin-1 and LC3 increased,while the expression of Bcl-2 and P62 decreased in human periodontal ligament cells of the H2O2 group.Compared with the H2O2 group,the expressions of Caspase-3,Bax,Beclin-1 and LC3 decreased,and the expressions of Bcl-2 and P62 increased in the H2O2+Rg1 group.(4)Compared with the control group,the expressions of PI3K,AKT and mTOR decreased in human periodontal ligament cells of the H2O2 group.Compared with the H2O2 group,the expressions of PI3K,AKT and mTOR increased in human periodontal ligament cells of the H2O2+Rg1 group.(5)These results suggest that ginsenoside Rg1 can inhibit H2O2-induced apoptosis and autophagy in human periodontal ligament cells by reducing the content of reactive oxygen species and down-regulating the related factor expression of the PI3K/AKT/mTOR pathway.