Objective: To understand the current status of neglect among rural preschool children in Xi an under the multi child policy and the association with family characteristics, so as to provide a reference for preventing and reducing the occurrence of child neglect. Methods: A total of 7 052 parents of preschool children were selected using stratified cluster sampling across 9 suburban counties/districts in Xi an from March to April 2025. A questionnaire survey was administered using the Chinese Norm Scale for Neglect Assessment of Rural(Preschool) Children Aged 3-6. The t-test, Chi-quare test, and analysis of variance (ANOVA) were used for inter group comparisons. Results: The overall prevalence rate and mean score of neglect among rural preschool aged children in Xi an were 32.4% and 38.27±6.70, respectively. Statistically significant differences were detected in neglect rates and neglect degrees among preschool children of different genders and grade levels ( χ 2=30.41, 15.15, t/F =4.92,7.03, all P <0.05). Statistically significant differences were also detected in neglect rates and neglect degrees among preschool children from whether only one child, different family structures, numbers of children in a family and families with different annual incomes ( χ 2=29.22, 10.41 , 31.99, 186.47, t/F =-9.96, 5.50, 33.57, 68.63, all P <0.05). In multi child families, there was a statistically significant difference in neglect degree among children with different birth orders ( F =4.25, P <0.05), but there was no statistically significant difference in neglect rate ( χ 2=5.73, P >0.05). Among all subgroups, the highest neglect rates and neglect degrees were observed in children from multi child families(35.0%,39.00±6.71), other family types(50.0%，42.38±12.34) and families with three children(39.9%，39.50±7.43). Lower annual family income was associated with higher neglect rates and neglect degrees among preschool children( χ 2 trend =186.47， F =270.68，both P <0.05). Conclusions Under the multiple child policy, the neglect of preschool children in rural areas of Xi an is quite severe, particularly in families with multiple children and low income households. Targeted interventions should be implemented for high risk groups.

Objective To explore the predictive performance of machine learning models integrating clinico-pathological features and inflammatory markers for lymphovascular invasion (LVI) before gastric cancer surgery. Methods A retrospective cohort of 193 gastric cancer patients from The First Hospital of Lanzhou University (training set) and 185 patients from Zhongshan Hospital, Fudan University (validation set) was included. Preoperative clinical pathological characteristics, tumor markers, and inflammatory markers were collected to identify independent risk factors for LVI. Six machine learning models were established in the training set. Model performance was evaluated using area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, decision curve analysis (DCA), and Brier scores. Shapley additive explanations (SHAP) was applied for model interpretability. Results The multivariate logistic regression showed increased tumor invasion depth (T-stage), lymph node metastases (N-stage), and the systemic immune-inflammation index (SII) were independent risk factors for gastric cancer LVI (P＜0.05). Using these three indicators, 6 machine learning models were developed, all of which demonstrated favorable predictive performance, with 0.79 and 0.76 of minimum AUC values in the training set and the validation set, respectively. Among them, the light gradient boosting machine (LightGBM) model exhibited the best overall performance, achieving AUCs of 0.83 and 0.82 in the training set and the validation set, along with Brier scores of 0.163 and 0.187, respectively. Calibration and DCA curves further confirmed that the model possesses strong predictive accuracy and application value. SHAP analysis showed the feature importance in LightGBM model, identifying the N-stage as the top contributor, followed by the T-stage and the SII. Conclusion The machine learning models incorporating clinical pathological features and inflammatory indicators can effectively predict LVI status in gastric cancer, with the LightGBM model demonstrating optimal performance.

Metabolic associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， and its progression is closely associated with the development of liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. However， there is still a lack of effective therapies for MAFLD in clinical practice. Telomere is the protective structure at the end of chromosomes， and telomere shortening and functional impairment have been identified as one of the key factors regulating the pathological progression of MAFLD. This article systematically reviews the core mechanism of action of telomere regulation in MAFLD， including its molecular functions in nucleotide metabolism， oxidative stress， and epigenetic regulation， as well as its pathological effect in hepatocytes and hepatic stellate cells. In addition， this article explores the clinical prospects of telomeres as biomarkers and therapeutic targets for MAFLD， in order to provide a theoretical reference for improving the precise diagnosis and treatment system of MAFLD.

Owing to physical and mental immaturity， children require special protection in medical research. With the rise of real-world research， ethical issues such as informed consent， privacy protection， and risk-benefit assessment have become particularly prominent in pediatric studies due to diverse data sources and complex study designs. Although institutional review boards constitute the primary safeguard for research ethics， journal editors play an irreplaceable role in pre-publication ethical gatekeeping. From the perspective of journal editors， this paper reviewed common ethical risks in pediatric real-world research， including the lack of scientific value in research topics， unjust control groups， inadequate privacy protection， and other issues. Based on the four principles of biomedical ethics and the three-tier review process， this study constructed a structured ethical review framework. The framework comprised three levels： basic compliance screening at the initial review， substantive risk assessment and grading at the secondary review， and escalated handling of high‑risk manuscripts at the final review， and it achieved a transformation from formal compliance verification to substantive ethical assessment led by risk grading. This could provide effective ethical risk assessment tools for journal editors and offer references for medical journals to improve pre-publication ethical governance.

OBJECTIVES: To explore the therapeutic mechanism of Flos Sophorae (FS) for treatment of psoriasis. METHODS: The active ingredients, targets and psoriasis-related disease targets of FS were obtained from TCMSP, GeneCards, OMIM, DisGeNET and String databases, and Cytoscape 3.8.0 software was used to construct the "FS -active ingredient-key target-signaling pathway-psoriasis" network. GO and KEGG enrichment analyses of the key targets were conducted, and molecular docking was performed using Discovery Studio 2019. In a BALB/c mouse model of imiquimod-induced psoriasis, the effects of vaseline, FS at high, medium and low doses (3.00, 1.50 and 0.75 g/kg, respectively) and a positive drug, given 1 week before and during modeling, were evaluated on body weight changes, spleen coefficient, psoriasis area and severity index (PASI) score and skin pathological changes. Phosphorylation levels of PI3K and AKT proteins were detected using immunohistochemistry and Western blotting. RESULTS: A total of 10 active components and 110 key targets were screened. GO and KEGG pathway enrichment analysis suggested that FS improved psoriasis primarily through the PI3K/AKT, TNF, and IL-17 signaling pathways. Molecular docking showed that both quercetin and kaempferol could spontaneously bind to AKT1, TNF and other sites. In the mouse model of psoriasis, treatment with low-dose FS significantly improved epidermal thickening, increased body weight, lowered PASI score, and reduced phosphorylation levels of PI3K and AKT proteins. CONCLUSIONS The therapeutic mechanism of FS for psoriasis involves multiple components, targets, and pathways that mediate the inhibition of the phosphorylation levels of PI3K and AKT proteins to suppress the activation of the PI3K/AKT signaling pathway.
Animals ; Psoriasis/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Signal Transduction/drug effects* ; Mice, Inbred BALB C ; Phosphatidylinositol 3-Kinases/metabolism* ; Molecular Docking Simulation ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Imiquimod ; Phosphorylation

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

OBJECTIVE To systematically evaluate the efficacy and safety of Insulin degludec and liraglutide injection （IDegLira） and Insulin glargine and lixisenatide injection（iGlarLixi） in the treatment of type 2 diabetes mellitus（T2DM）， and provide an evidence-based basis for the clinical treatment of T2DM. METHODS Computerized searches of PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP were conducted with a time frame from the inception to August 2024. Randomized controlled trials（RCTs） were rigorously screened according to inclusion and exclusion criteria， from which information was extracted and included studies were evaluated for risk of bias. Network meta-analysis was performed using Stata 14.0 software. RESULTS A total of 15 RCTs， including 9 513 patients， were included， involving four treatment regimens： IDegLira， iGlarLixi， insulin degludec（IDeg）， and insulin glargine（iGlar）. The differences between IDegLira and iGlarLixi were not statistically significant（P＞0.05） for the outcome indexes of glycosylated hemoglobin（HbA1c）， fasting blood glucose， body weight， and the incidence of adverse events（P＞0.05）； for the outcome index of the incidence of hypoglycemic events， IDegLira was significantly superior to iGlarLixi [OR＝0.41，95%CI（0.18，0.91），P＜0.05]. Surface under the cumulative ranking curve（SUCRA） results showed that iGlarLixi（84.5%）＞IDegLira（81.7%） in lowering HbA1c； IDegLira（71.3%）＞iGlarLixi（20.0%） in lowering fasting blood glucose； IDegLira（90.7%）＞iGlarLixi（61.8%） in lowering body weight； IDegLira（95.5%）＞iGlarLixi（9.7%） in reducing the incidence of hypoglycemic events； and IDegLira（27.1%）＞iGlarLixi（14.5%） in reducing the incidence of adverse events. CONCLUSIONS iGlarLixi has better therapeutic efficacy in reducing HbA1c； IDegLira has better therapeutic efficacy in reducing fasting blood glucose and body weight. IDegLira has the lowest risk of hypoglycemia.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Objective·To establish a research framework for serotonylation of proteins and to provide a methodological basis for the identification of serotonylated proteins.Methods·The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of the transglutaminase 2(TGM2)gene,which encodes the key enzyme for serotonylation,and the solute carrier family 6(SLC6A4)gene,which encodes the serotonin transporter(SERT),in normal and pan-cancer tissues.5-Propargyltryptamide(5-PT),a serotonin derivative,was synthesized stepwise from serotonin hydrochloride,and its structure was characterized by the Fourier transform infrared spectroscopy(FT-IR),proton nuclear magnetic resonance(1H-NMR),carbon nuclear magnetic resonance(13C-NMR),and time-of-flight mass spectrometry(TOF-MS).The intracellular uptake of 5-PT in the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and bone marrow-derived macrophages(BMDMs),was detected by using flow cytometry.Click chemistry,co-immunoprecipitation,and mass spectrometry analysis techniques were employed to identify serotonylated proteins,and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results·Bioinformatics analysis indicated that TGM2 and SLC6A4 were widely expressed in various normal tissues and across pan-cancer tissues.The flow cytometry results showed that the synthesized 5-PT can be taken up into the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and BMDMs,via the SERT.Mass spectrometry analysis data showed that a significant amount of serotonylated proteins were enriched in various cells treated with 5-PT.KEGG enrichment analysis revealed that these proteins were involved in important pathways related to glycolysis and amino acid synthesis.Conclusion·By using the synthesized 5-PT,multiple serotonylated proteins are enriched in various cell types.A research system for identifying serotonylated proteins has been successfully established,providing a relatively simple and efficient method for studying protein serotonylation.

Objective To investigate the relationship between the levels of serum suppressor of cytokine signaling 3(SOCS3),growth differentiation factor-15(GDF-15)and liver fibrosis in patients with type 2 dia-betes mellitus(T2DM)combined with non-alcoholic fatty liver disease(NAFLD).Methods A total of 320 patients with T2DM combined with NAFLD who were hospitalized in this hospital from May 2023 to May 2024 were selected as the study group,and another 320 patients with simple T2DM admitted during the same period were selected as the control group.The levels of serum SOCS3 and GDF-15 were determined by en-zyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the correlation between SOCS3,GDF-15 levels and liver fibrosis indicators.Logistic regression analysis was used to analyze the factors affecting the degree of liver fibrosis.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum SOCS3 and GDF-15 for the degree of liver fibrosis in patients.Results Compared with the control group,the levels of serum SOCS3,GDF-15,5,type Ⅲ procollagen peptide,laminin and type Ⅳ col-lagen in the study group were significantly increased(P＜0.05).There were statistically significant differ-ences in the levels of type Ⅲ procollagen peptide,laminin and type Ⅳ collagen between the mild to moderate group and the severe group(P＜0.05).Compared with the mild to moderate group,the levels of serum SOCS3 and GDF-15 in the severe group were significantly increased(P＜0.05).The results of Pearson corre-lation analysis showed that serum SOCS3 and GDF-15 in patients with T2DM combined with NAFLD were positively correlated with type Ⅲ procollagen peptide,laminin,and type Ⅳ collagen(P＜0.05).Serum SOCS3,GDF-1 5,type Ⅲ procollagen peptide,laminin and type Ⅳ collagen are risk factors affecting the degree of liver fibrosis in patients with T2DM combined with NAFLD(P＜0.05).The results of the ROC curve showed that the combined diagnosis of serum SOCS3 and GDF-15 for the degree of liver fibrosis in patients with T2DM complicated with NAFLD had the highest area under the curve(AUC),which was superior to the individual diagnosis of each(both P＜0.05),with a corresponding sensitivity of 69.08％and a specificity of 85.71％.The combined diagnosis of the degree of liver fibrosis in patients with T2DM complicated with NAFLD by serum SOCS3,GDF-15,type Ⅲ procollagen peptide,laminin,and type Ⅳ collagen had the highest AUC,which was superior to the individual diagnosis of each index(all P＜0.001),with a corresponding sensi-tivity of 89.47％and a specificity of 97.02％.Conclusion The levels of serum SOCS3 and GDF-15 are elevated in patients with T2DM combined with NAFLD,.The combined diagnosis of serum SOCS3,GDF-15,type Ⅲ procolla-gen peptide,laminin,and type Ⅳ collagen has a high value in the degree of liver fibrosis in patients.