ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Objective To explore the predictive value of methylenetetrahydrofolate reductase(MTHFR)gene C677T polymorphism and serum homocysteine(Hcy)level for adverse pregnancy outcomes.Methods The clinical data of 698 pregnant women who received antenatal care and deliv-ered at Ji'an Central People's Hospital were retrospectively collected.According to the research pur-pose,the pregnant women were divided into internal study cohort(n=483)or external validation co-hort(n=215).Each cohort was further divided into adverse pregnancy group and normal pregnancy group based on whether adverse pregnancy outcomes occurred.The MTHFR gene C677T polymor-phism and serum Hcy level of all pregnant women were detected.Binary Logistic regression analysis was used to investigate the relationships of MTHFR gene C677T polymorphism,Hcy level,and other indicators with adverse pregnancy outcomes.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive efficacy of different indicators when used alone and their combina-tion.Results In the internal study cohort,compared with the normal pregnancy group,the detection frequency of the CC genotype at the MTHFR gene C677T locus was lower,while the detection frequencies of the CT and TT genotypes were higher in the adverse pregnancy group(P＜0.001).The proportion of pregnant women with high Hcy levels was higher in the adverse pregnancy group than that in the normal pregnancy group(P＜0.001).Binary Logistic regression analysis showed that age,folic acid level during pregnancy,MTHFR gene C677T polymorphism,and Hcy level were all independ-ent influencing factors for adverse pregnancy outcomes(P＜0.05).The ROC curve indicated that the area under the curve(AUC)of the combined prediction model was 0.938,which was greater than that of each indicator.In the external validation cohort,the AUC of the combined prediction model was 0.917,validating the stability and clinical applicability of the model.Conclusion The TT and CT genotypes at the MTHFR gene C677T locus and high Hcy level are all independent risk factors for adverse pregnancy outcomes.The prediction model constructed by combining these factors with age and folic acid level during pregnancy has a high predictive efficacy for adverse pregnancy outcomes.

Objective:To investigate the temporal expression of Growth Differentiation Factor-15 (GDF15) in the serum of patients with Acute Coronary Syndrome (ACS) and explore the clinical significance of GDF15 in protecting cardiomyocytes in ACS.Methods:A retrospective study was conducted on 289 ACS patients admitted to the emergency departments from February to October 2023. Data on gender, age, troponin T (TnT), creatine kinase isoenzyme (CK-MB), GDF15, and B-type natriuretic peptide (BNP) within 30 minutes of admission were recorded. Differences in these indicators among different groups were compared. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the diagnostic value of GDF15, TnT, and BNP for ACS. Among the patients, 15 exhibited a temporal expression pattern of GDF15, and their blood samples were re-measured using a GDF15 fluorescent quantitative immunochromatographic assay kit. Fifteen patients without temporal expression were randomly selected as controls, and their samples were also re-measured to exclude detection errors. Fifteen patients with temporal expression were included in the temporal expression group, and 15 without temporal expression were included in the non-temporal expression group. Laboratory indicators such as fasting blood glucose, glycated hemoglobin, triglycerides, creatinine, and uric acid were compared between the groups. Additionally, patient age, gender, body mass index (BMI), coronary angiography results, echocardiography, Gensini score, left ventricular ejection fraction (LVEF), and GRACE risk score were recorded to assess their correlation with GDF15 temporal expression. Statistical analysis was performed using SPSS 27 software, with continuous data expressed as mean ± standard deviation (Mean ± SD) and compared using t-tests and χ2 tests. Results:The overall trend in ACS patients showed a higher proportion of males than females (73.36% vs. 26.64%). The oldest group was the Unstable Angina (UA) group, with a mean age of (63.98 ± 15.19) years, while the youngest group was the non-ACS chest pain group, with a mean age of (54.29 ± 16.39) years. A higher proportion of patients in the UA, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) groups had a history of smoking. The combination of GDF15 and TnT showed high diagnostic value for ACS, with an area under the ROC curve (AUC) of 0.843, consistent with previous studies. Among all ACS patients, 15 exhibited a temporal expression pattern of GDF15, where GDF15 levels peaked at 4 hours, gradually decreased, and peaked again at 24 hours. Patients in the temporal expression group had higher LVEF and left ventricular end-systolic diameter compared to the non-temporal expression group. The Gensini score was lower in the temporal expression group, and the GRACE risk score was significantly lower in the temporal expression group (00.7±14.72) compared to the non-temporal expression group (116.1±23.46), with a statistically significant difference ( P = 0.0115). There were no significant differences in general characteristics (age, gender, BMI) or clinical biochemical indicators (fasting blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid) between the temporal and non-temporal expression groups ( P > 0.05). Conclusions:GDF15 demonstrates significant diagnostic and prognostic predictive value in ACS. Patients with temporally dynamic expression of serum GDF15 exhibit milder myocardial injury and a lower probability of mortality. These findings provide novel therapeutic targets and research directions for further exploring the role of GDF15 in ACS management.

Objective To compare the diagnostic efficacy of biparametric magnetic resonance imaging(bp-MRI)and multiparametric magnetic resonance imaging(mp-MRI)for prostate cancer among radiologists with different levels of experience.Methods A retrospective analysis was conducted on MRI data of 112 suspected prostate cancer patients.Six radiologists(2 in the primary,intermediate,and advanced groups)used the bp-MRI and mp-MRI protocol scores to analyze the diagnostic efficacy.Results The area under the curve(AUC)of diagnostic efficacy in the advanced group of the bp-MRI protocol was greater than that in the intermediate group(P=0.024),and the intermediate group was greater than that in the primary group(P=0.046).The intermediate group of the mp-MRI protocol was greater than the primary group(P=0.043),while there was no difference between the intermediate and advanced groups(P=0.221).As the experience of the radiologists increased,sensitivity also increased,but there was no significant change in specificity.There was no difference between the two protocols in the advanced group(AUC=0.826-0.866;P＞0.05);while the mp-MRI protocol performance was better in the primary and intermediate groups(AUC=0.705-0.815;P＜0.05).Conclusion Experienced radiologists can choose the bp-MRI protocol,while inexperienced radiologists are more suitable for the mp-MRI protocol.Based on the accumulated experience of radiologists,protocol optimization and adjustment can be carried out at appropriate times.

Objective:Bioinformatics was used to analyze the gene expression profile of renal chromophobe cell carcinoma (RCCC) to find out the key genes of RCCC.Methods:Chromophobe renal cell carcinoma gene chip data GSE15641 and GSE11151 were downloaded from the GEO database. Using R software packages such as " Affy" and " limma" in R software to screen differentially expressed genes, combining with David and STRING online bioinformatics tools to analyze the regulatory network of differentially expressed genes and construct protein-protein interaction (PPI) network, the Hub gene was screened through the Cytohubba plug-in of Cytoscape software.Results:A total of 261 differentially expressed genes were screened, including 194 down-regulated genes and 67 up-regulated genes. Gene enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore their biological functions. In GO enrichment analysis, biological processes were mainly enriched in cell secretion, gluconeogenesis and cell proliferation regulation; in cell composition, they were mainly enriched in exosomes, plasma membranes and their components; in molecular function, they were mainly enriched in heparin binding; in KEGG pathway analysis, they were mainly enriched in metabolic pathway, antibody biosynthesis pathway and renin angiotensin system pathway. PPI network was constructed by using online bioinformatics tools. The top 10 Hub genes were screened by using cytohubba plug-in in Cytoscape software, which were pipecolic acid and sarcosine oxidase (PIPOX), hydroxyacid oxidase 2 (HAO2), kynurenine 3-monooxygenase (KMO), solute carrier family 2 member 2 (SLC2A2), formimidoyltransferase cyclodeaminase (FTCD), angiogenin (ANG), APOBEC1 complementation factor (A1CF), aldehyde dehydrogenase 8 family member A1 (ALDH8A1), vitamin D binding protein (GC), histidine rich glycoprotein (HRG).Conclusions:Bioinformatics analysis of differentially expressed genes in renal chromophobe cell carcinoma can effectively explore the interaction information of these differentially expressed genes, and provide new ideas for the treatment of renal chromophobe cell carcinoma.

Objective:To investigate the value of histogram analysis of ultrasound gray scale in differential diagnosis of triple negative breast invasive ductal carcinoma (TN-IDC) and non-triple-negative breast invasive ductal carcinoma (NTN-IDC).Methods:Totally 195 patients with invasive ductal carcinoma confirmed by pathology in Hubei Cancer Hospital from September 2017 to July 2020 were retrospectively analyzed.According to immunohistochemical results after surgery, 195 patients were divided into TN-IDC group ( n=44) and NTN-IDC group ( n=151). All cases were retrospectively analyzed to observe the ultrasonoscopy histogram features of tumors and obtain the histogram parameters, including mean, variance, skewness, kurtosis and percentile gray-scale values. The histogram parameters of TN-IDC were compared with those of NTN-IDC. The ROC curves were constructed to observe the efficiency of differential diagnosis. Results:The values of variance, 90th and 99th percentiles in TN-IDC group were much lower than those in NTN-IDC group (all P<0.05). The values of mean, skewness, kurtosis and other percentile (1st, 10th, and 50th) values between the two groups were not significantly different(all P>0.05). The optimal cutoff value for the accurate identification of TN-IDC and NTN-IDC groups was 552.85 for variance[sensitivity 75.0%, specificity 79.5%, positive predictive value(PPV) 51.6%, negative predictive value(NPV) 91.6%, accuracy 78.5%, and area under curve 0.829, respectively]. The optimal cutoff value for the accurate identification of TN-IDC and NTN-IDC groups was 74 for 90th percentile (sensitivity 68.2%, specificity 57.6%, PPV 31.9%, NPV 86.1%, accuracy 60.0%, and area under curve 0.648, respectively). The optimal cutoff value for the accurate identification of the two groups was 107 for 99th percentile (sensitivity 75.0%, specificity 77.5%, PPV 49.3%, NPV 91.4%, accuracy 76.9%, and area under curve 0.772, respectively). Conclusions:Histogram analysis of ultrasound gray scale can provide certain value for the differential diagnosis of TN-IDC and NTN-IDC, the variance and 99th percentile values could perform better.

Objective: To analyze the correlation between behavior and lifestyle factors and anxiety symptoms of left-behind children, and to provide evidence for mental health intervention of left-behind children. Methods: 1 188 children aged from 13 to 18 (617 non-left-behind children and 571 left-behind children) in B County of Shangrao City, Jiangxi Province were evaluated with Generalized Anxiety Disorder Scale (GAD-7). Meanwhile, physical activity, TV watching time, computer usage time, dietary behavior, sleep and other behavioral lifestyle factors of left-behind children were investigated by questionnaire. Results: The detection rate of anxiety among left-behind children (66.0%) was higher than that of non-left-behind children (60.5%). The detection rates of mild, moderate, and severe anxiety were 26.3%, 15.4% and 24.3%, respectively. Under the condition of controlling age and gender, Logistic regression analysis showed that left-behind childrens anxiety symptoms and computer usage time>3 h/d (mild anxiety, OR=3.00, 95%CI=1.27-4.16; moderate anxiety, OR=4.09, 95%CI=1.55-10.78; severe anxiety, OR=3.44, 95%CI=1.46-8.11), mobile phone usage time >3 h/d (mild anxiety, OR=4.93, 95%CI=2.71-8.94; moderate anxiety, OR=5.93, 95%CI=2.98-11.79; severe anxiety, OR=7.11, 95%CI=3.85-13.15), skipping breakfast behavior (moderate anxiety, often skipping, OR=6.09, 95%CI=1.59-23.36; severe anxiety, often skipping, OR=5.49, 95%CI =1.68-7.97, sometimes eat breakfast, OR=2.68, 95%CI=1.10-6.53) was positively correlated; with appropriate sleeping time (moderate anxiety, OR=0.28, 95%CI=0.13-0.60) was negatively correlated. Conclusion The unhealthy behavior and lifestyle of left-behind children may be a potential risk factor for anxiety symptoms.

Objective:To investigate the associations of brain white matter integrity deficits, and to explore the association of fractional anisotropy (FA) abnormality with clinical symptoms and cognitive impairments, as well as the prediction effect of the FA alterations on symptoms and cognitive function outcomes in the acute stage of schizophrenia from the whole brain level based on magnetic resonance diffusion tensor imaging (DTI).Methods:From November 2019 to December 2020, thirty-eight patients with first-episode schizophrenia and 38 healthy controls were recruited in this study. Wisconsin card classification test (WCST), digit span test (DST forward/backward), verbal fluency test, Stroop (A/B/C), trail making test (TMT-A/B), as well as positive and negative syndrome scale (PANSS) were utilized to evaluate patients' cognitive function and clinical symptoms both before and after 8 weeks of risperidone monotherapy. T1-weighted images and DTI data of all the subjects were collected . FSL and SPM8 were used to preprocess MRI data and compare the between-group differences of FA. Support vector machine (SVM) analysis was used to evaluate the accuracy of abnormal FA values in differentiating schizophrenic patients from healthy controls. Finally, stepwise multiple regression analysis or generalized linear models were used to explore the associations between white matter integrity and symptoms or cognition.Results:Before treatment, patients' FA values of right medial temporal lobe (mTL), cuneus, anterior cingulate gyrus (ACG) and inferior parietal lobe (IPL) were significantly lower than those in healthy controls ( P<0.01, GRF corrected), and patients' FA values of bilateral middle cingulate gyrus (mCG) were significantly higher than those in the control group ( P<0.01, GRF corrected). SVM analysis showed that four combinations could distinguish the patients from the control with the most accurate rate of 89.47%. Patients' baseline decreased FA values in the right IPL were positively associated with their increased total response time in WCST ( β=0.489, P=0.003, FDR corrected), correct response time in WCST ( β=0.450, P=0.008, FDR corrected), error response time in WCST ( β=0.435, P=0.008, FDR corrected), TMT-B ( β=0.296, P=0.042, FDR corrected), Stroop-C ( β=0.345, P=0.035, FDR corrected), and PANSS-P ( β=0.321, P=0.042, FDR corrected). Reduced FA values in the right mTL in patient group were significantly negatively related to the total time spent on the TMT-A ( β=-0.425, P=0.009, FDR corrected) and TMT-B ( β=-0.325, P=0.026 with FDR correction). Increased FA values in right mCG in patient group demonstrated positive associations with total response time in the WCST ( β=0.585, P=0.002, FDR corrected), correct response time in WCST ( β=0.524, P=0.003, FDR corrected), error response time in WCST ( β=0.536, P=0.003, FDR corrected) and total time consuming in TMT-B ( β=0.484, P=0.004, FDR corrected), as well as negative associations with DST-forward ( β=-0.319, P=0.042, FDR corrected). After treatment, patients' percentage changes in total response time of WCST ( β=0.715, P<0.001, FDR corrected), correct response time of WCST ( β=0.752, P<0.001, FDR corrected), as well as total time-consuming of TMT-A ( β=1.333, P=0.001, FDR corrected) showed positive correlations with baseline increased FA values in the left mCG. Percentage alteration of Stroop-B was negatively correlated with baseline FA values in the right cuneus ( β=-0.745, P=0.015, FDR corrected). Conclusions:The combination of abnormal FA values in multiple brain regions may be potential biomarkers to distinguish schizophrenic patients from healthy volunteers. There was regional dependence in the associations of the impairment of white matter integrity with the cognitive impairment, the severity of psychopathological symptoms as well as the prognosis of patients in the acute stage.

Objective:To examine the relationship between pre-pregnancy BMI, gestational diabetes (GDM) and different indicators of childhood obesity at the age of 4.Methods:Based on Ma’anshan Birth Cohort Study, singleton children who were born in Ma’anshan of Anhui province from October 2013 to April 2015, were followed for 4 years, consecutively. During the first questionnaire survey, data including pre-pregnancy weight, height and socio-demography were collected. During 24-28 week of gestation, 75 g oral glucose tolerance test was conducted for them. Childhood height, weight, waist circumference and body composition were measured at the age of 4. Comparisons between groups were performed using chi-square test, analysis of variance or t-test. The relationship between pre-pregnancy overweight/obesity, GDM and childhood obesity-related characteristics were analyzed by logistic regression model and generalized linear model analysis. Results:The prevalence rates of overweight and obesity in children at the age of 4 were 13.08% and 6.03%, respectively. After adjustment for characteristics related to mothers and their children, significantly increased risk of obesity ( OR=3.27, 95% CI: 2.15-4.98), larger waist circumference ( OR=2.32, 95% CI: 1.72-3.14) and higher waist-to-weight ratio ( OR=2.29, 95% CI: 1.73-3.02) were seen in the offspring of women with pre-pregnancy overweight/obesity. Body composition (skeletal muscle, body fat, body fat percentage) of the offspring were strongly correlated with pre-pregnancy overweight/obesity of the mothers ( P<0.05). Maternal GDM was associated with higher risk of childhood obesity ( OR=1.78, 95% CI: 1.14-2.79), on mothers without GDM during pregnancy. However, neither larger waist circumference, or higher waist-to-weight ratio seemed to increase the risk. Moreover, maternal GDM was not associated with body composition measures (skeletal muscle, body fat, body fat percentage). Conclusion:Pre-pregnancy BMI and maternal GDM were independent risk factors for obesity in 4-year-old children, and pre-pregnancy BMI was correlated with various indicators of body composition in children.