ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Objective: To explore the association of health literacy with overweight and obesity among middle school students in Chongqing, so as to provide evidence for obesity prevention and control strategies. Methods: From November to December 2019, a stratified cluster sampling method was used to select 7 851 middle school students from 8 complete middle schools across 4 districts/counties in Chongqing. Participants completed the Adolescent Health Literacy Questionnaire and underwent nutritional status assessments. Chisquare tests and multivariate Logistic regression analyses were performed to evaluate associations. Results: The prevalence of overweight and obesity among adolescents was 12.95%. The overall health literacy rate and rates for functional, interactive, and critical health literacy dimensions were 62.01%, 66.02%, 50.07%, and 72.42%, respectively. Significant differences in overweight and obesity prevalence were observed across districts/counties, urban/rural areas, sex, school stages, and onlychild status (χ2=25.93, 3.86, 80.55, 8.80, 6.43, P<0.05). After adjusting for confounding factors, multivariate Logistic regression revealed that middle school students with overall health literacy (OR=0.86, 95%CI=0.75-0.99), interactive health literacy (OR=0.85, 95%CI=0.74-0.97), and critical health literacy (OR=0.84, 95%CI=0.73-0.98) had a lower risk of overweight and obesity (P<0.05). Conclusions Health literacy is inversely associated with overweight and obesity among middle school students. Strengthening health education and improving interactive and critical health literacy may create favorable conditions for adolescent overweight and obesity prevention and control.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Background Indoor air quality directly affects people's health, especially the impact of chemical pollutants in residential indoor air on children and the elderly is more significant. Objective To understand the pollution status of common chemical pollutants in residential indoor air in Shijiazhuang, evaluate the health risks of chemical pollutants to school-age children and the elderly, and provide reference for controlling indoor pollution in residential environment. Methods Using stratified random sampling, a total of 60 households were selected from 2 urban areas and 1 surrounding rural area in Shijiazhuang City, specifically in July 2023 (non-heating season) and December 2023 (heating season), respectively. Relevant data was collected through on-site sampling [including CO, CO₂, PM₁₀, PM_2.5, NO₂, SO₂, O₃, ammonia, formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), trichloroethylene, and tetrachloroethylene] and survey questionnaires. The pollutant concentrations were evaluated following the Standards for indoor air quality of GB/T 18883-2022, and the inhalation exposure risks of the target population were assessed based on the health risk assessment method. Results In the indoor air of the urban and rural residence in Shijiazhuang City, except for CO, NO₂, SO₂, toluene, and xylene, which did not exceed the standard limits, other pollutants showed varying degrees of exceedance. The non-qualified rates of PM₁₀, PM_2.5, and CO₂ in the urban areas were higher than those in the rural areas (P < 0.05). The seasonal difference analysis showed that the non-qualified rates of PM_2.5, PM₁₀, CO₂, trichloroethylene, and tetrachloroethylene in the urban areas were higher in the heating season than in the non-heating season (P<0.05); the non-qualified rates of ammonia and formaldehyde in the rural areas increased significantly in the non-heating season(P<0.05). The health risk assessment indicated that the maximum hazard quotient (HQ) of tetrachloroethylene for the elderly exceeded 1, while the HQ values for ammonia, formaldehyde, benzene, toluene, xylene, and trichloroethylene remained below 1 for either children or the elderly. For carcinogenic risks, the median carcinogenic risk (CR) of formaldehyde for school-aged children or the elderly fell within the range of 10⁻⁶-10⁻⁴, whereas the median CR values for benzene, trichloroethylene, and tetrachloroethylene were all below 10⁻⁶. Conclusion The primary indoor air pollutants exceeding the national standard limits in residential areas of Shijiazhuang City include CO₂, PM₁₀, TVOC, PM_2.5, formaldehyde, ammonia, trichloroethylene, and tetrachloroethylene. The levels of these pollutants exhibit significant urban-rural and seasonal variations. Special attention should be paid to the non-carcinogenic risk of tetrachloroethylene to the elderly and the carcinogenic risks of formaldehyde to school-age children and the elderly.

Objective: To investigate the role of ferroptosis in transfusion-related acute lung injury (TRALI) and evaluate the efficacy of the specific inhibitor Ferrostatin-1 (Fer-1), thereby to provide a basis for the prevention and treatment of TRALI. Methods: This study utilized a ”2-hit” model to induce TRALI in mice. The mouse model of TRALI was validated through survival curve analysis, lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity, and total protein concentration in lung tissue. Samples from the TRALI model group, LPS group, and control group (n=6) were collected. The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators, including iron concentration in lung tissue, malondialdehyde (MDA) level, lipid peroxidation products (LPO) level, and expression levels of related proteins (GPX4, ACSL4). Additionally, a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects. The survival rates and clinical symptoms of the four groups (n=6) were dynamically monitored, and the degrees of lung injury were assessed. Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1. Results: A mouse model of TRALI was successfully established. Compared to the control and LPS groups, the TRALI group showed significantly higher levels of ferrous iron [(18.32±1.11) nmol/well, MDA [(14.68±0.96) μmol/L], and LPO [(1.60±0.02) μmol/L] in lung tissue (all P<0.01), along with a downregulation of GPX4 and an upregulation of ACSL4. Fer-1 pretreatment significantly reversed these abnormalities: the W/D ratio decreased to 4.01±0.43, and MPO activity significantly decreased [Fer-1 group: (21 606±4 235) pg/mL vs TRALI group: (30 724±2 616) pg/mL], the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8% compared to the TRALI group (all P<0.01). These changes indicate that the lung injury in mice was alleviated after treatment. Following Fer-1 intervention, ferrous iron concentration [(7.46±1.83) nmol/well] was restored to a level close to that of the control group [(5.48±0.70) nmol/well]. Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8% and 29.4%, respectively (P<0.001). Additionally, the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice (both P>0.05). Conclusion: The progression of TRALI is closely related to the activation of ferroptosis, characterized by iron overload, lipid peroxidation accumulation, and the imbalance of GPX4/ACSL4. Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway, suggesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.

Objective: To explore the independent effects and gender differences of different types of adverse childhood experiences (ACEs) on the co-occurrence of non-suicidal self-injury (NSSI) and suicide attempts (SA), so as to provide a reference for the precise prevention and control of self-harm in junior high school students. Methods: From May to June 2023, a total of 7 360 junior high school students were selected from 12 schools in three districts/counties of Chongqing using a combination of stratified cluster sampling and convenience sampling methods. Information on NSSI, SA, ACEs, and depressive symptom, as well as other related data were collected through the Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSAQ), suicide related section of the Chinese Adolescent Health related Behavior Questionnaire (Junior High School Version), Childhood Trauma Questionnaire-Short Form ( CTQ- SF), and Center for Epidemiologic Studies-Depression Scale (CES-D). Statistical analyses of the data were performed using the Chi-square test and multiple Logistic regression. Results: The detection rates of NSSI, SA, NSSI+SA and ACEs in junior high school students were 19.2%, 4.6%, 3.5% and 57.9% respectively. After controlling for factors such as gender, grade, family type, self rated family economic status, self rated academic performance, self rated academic pressure, number of close friends, and depressive symptom scores, results from the multiple Logistic regression analysis showed that junior high school students with physical abuse ( OR = 1.98, 95% CI =1.23-3.18), emotional abuse ( OR =2.83, 95% CI =1.92-4.19), sexual abuse ( OR = 1.70, 95% CI =1.07- 2.69 ), physical neglect ( OR =1.67, 95% CI =1.20-2.33) and witnessing domestic violence ( OR =2.10, 95% CI =1.41-2.87) in childhood had higher risks for the occurrence of NSSI+SA (all P <0.05). After stratification by gender, boys with sexual abuse in childhood had a high risk for the occurrence of NSSI+SA ( OR =2.17, 95% CI =1.06-4.43), whereas girls with emotional abuse ( OR =3.69, 95% CI =2.29-5.94), physical neglect ( OR =1.62, 95% CI =1.07-2.45) and witnessing domestic violence ( OR =2.17, 95% CI =1.41-3.34) in childhood had hgih risks for the occurrence of NSSI+SA (all P <0.05). Conclusions Different types of ACEs have different effects on the co-occurrence of self-harm in junior high school students and there are gender differences. When family interventions are conducted for the combined model, emphasis should be placed on aspects of emotional abuse and domestic violence while optimizing the interventions based on gender differences.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

[摘 要] 目的：基于临床病历信息系统，采用数据挖掘方法从真实世界角度分析中医药非介入治疗肺恶性肿瘤的辨治规律。方法：收集2015年1月1日至2021年12月31日北京中医药大学东直门医院病历系统中诊断为肺恶性肿瘤的患者病史、刻下症和用药信息，在剔除使用介入治疗手段的病例后建立数据库。采用Microsoft Office Excel 2019对高频药物的频数、四气五味、归经及功效进行描述性统计，并对病史和刻下症反映的症状进行数据化统计；对统计得到的高频药物和症状信息借助SPSS Modeler 18.0软件中Apriori算法对核心数据进行关联规则分析，并用Web节点构建关联网状图；借助SPSS Stastistics 23.0进行聚类分析。结果：共纳入119例未进行介入治疗的肺恶性肿瘤患者，中医常见症状为咳嗽、白痰、喘憋、纳差、眠差、痰黏、便秘、乏力、胸闷、气短；药物四气以温药最多；五味以甘味最多；归经以肺经频率最高。关联规则结果显示，二项支持度最高的组合为半夏→柴胡、半夏→瓜蒌、杏仁→麻黄；三项关联支持度最高的组合为半夏→茯苓、柴胡，杏仁→麻黄、半夏，半夏→杏仁、柴胡，半夏→瓜蒌、贝母。聚类结果聚为3类，依次为肺阴虚证、痰热壅肺证和肺气虚证。结论：中医药非介入治疗肺恶性肿瘤的中医药辨治规律为：聚类证型依次为肺阴虚证、痰热壅肺证和肺气虚证。治疗多用和解少阳、行气止咳平喘和清虚热化痰饮为主，药物以半夏、甘草、黄芩、茯苓、柴胡多见。

AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.