Objective:To explore the molecular mechanism by which the methionine adenosyltransferase 2A (MAT2A)/β-catenin/zinc finger E-box binding homeobox 1 (ZEB1)/epithelial-mesenchymal transition (EMT) pathway regulates neural tube defect (NTD) through intracellular S-adenosylmethionine (SAM).Methods:A mouse NTD model was induced using the SAM metabolic disorder inhibitor ethionine. Eighty specific pathogen-free C57BL/6 mice were divided into three groups: a normal group (36 mice), an ethionine group (46 mice), and an ethionine+SAM group (44 mice). Phosphate-buffered saline (PBS), ethionine, and ethionine+SAM were respectively injected intraperitoneally on embryonic day 7.5 (E7.5), and the mice were sacrificed on E10.5. Embryonic tissues were collected, and the morphology of embryos in each group was observed under a stereomicroscope. The interaction between ethionine and MAT2A was analyzed using Autodock software. The expression levels of MAT2A, β-catenin, ZEB1, and EMT-related proteins in the brain tissues of embryos from the three groups were measured using immunofluorescence, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (RT-qPCR). Variance analysis was used for intergroup comparisons.Results:(1) Autodock analysis results showed that MAT2A binds to ethionine through covalent bonds, exhibiting a complementary effect, thereby accelerating the expression of MAT2A. (2) After successful construction of the NTD model, normal embryos were plump with well-developed brains. NTD embryos showed delayed development, obvious anencephaly, unclosed neural tubes, and asymmetry. (3) The levels of SAM and SAH in the embryonic tissues of the ethionine group were significantly lower than those in the normal group (1 737.56±95.64 vs. 872.33±205.11, and 89.17±9.50 vs. 51.25±9.48, respectively). The SAM and SAH levels in the ethionine+SAM group was 1 197.00±222.27 and 66.61±12.25, significantly higher than those in the ethionine group ( P<0.017). Compared with the normal group and the ethionine+SAM group, the expression of MAT2A mRNA in the embryonic brain tissue of the ethionine group was significantly upregulated (1.00±0.00, 1.59±0.52, and 2.42±0.53, respectively, F=49.64, P<0.001; pairwise comparisons between groups P<0.017). (4) Compared with the normal group, the expression of Ctnnb1 in the ethionine group was reduced, and the expression of Ctnnb1 in the ethionine+SAM group was higher than that in the ethionine group (1.00±0.00, 0.38±0.16, and 0.76±0.10, respectively, F=149.03, P<0.001; pairwise comparisons between groups P<0.017). (5) The expression of ZEB1 in the ethionine group was higher than that in the normal group and the ethionine+SAM group (2.91±0.55, 1.00±0.00, and 1.61±0.20, respectively, F=150.01, P<0.001; pairwise comparisons between groups P<0.017). (6) The expression levels of E-cadherin and Vimentin in the ethionine group were lower than those in the normal group. In contrast, the expression of N-cadherin was higher than that in the normal group. After SAM supplementation, the expression levels of E-cadherin and Vimentin were upregulated, and the expression level of N-cadherin was downregulated (0.54±0.12, 1.00±0.00, and 0.72±0.14, respectively, F=87.44; 0.53±0.17, 1.00±0.00, and 0.76±0.09, F=87.44; 3.11±0.53, 1.00±0.00, and 2.13±0.56, F=95.54; all P<0.001; pairwise comparisons within the same index group P<0.017]). Conclusions:Ethionine promotes the expression of MAT2A, leading to reduced SAM production. Ethionine regulates the level of ZEB1 by increasing MAT2A and inhibits the EMT process to interfere with methionine cycle metabolism, ultimately resulting in NTD.

Objective To quantitatively assess the association of short-term exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient fine particulate matter (PM2.5) with residents mortality. Methods A time-stratified case-crossover study was conducted from 2020 to 2022 among 10606 non-accidental residents by using the Guangzhou Cause of Death Surveillance System in Conghua District, Guangzhou. Exposure levels of PAHs in PM_2.5 and meteorological data during the study period were obtained from the Center for Disease Control and Prevention in Conghua District and the China Meteorological Administration Land Data Assimilation System (CLDAS-V2.0), respectively. Conditional Poisson regression model was used to estimate the exposure-response association between PAHs and the mortality risk. Results Fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene, and indeno[1,2,3-cd]pyrene were significantly associated with an increased risk of mortality. For every one interquartile range increase in exposure levels, the non-accidental mortality risks increased by 8.33% (95% CI: 1.80%, 15.27%), 4.67% (95% CI: 1.86%, 7.57%), 6.07% (95% CI: 2.08%, 10.21%), 4.62% (95% CI: 1.85%, 7.47%), and 4.70% (95% CI: 0.53%, 9.03%), respectively. The estimated non accidental deaths attributable to exposure to fluoranthene, chrysene, benzo[k]fluorine, benzo[a]pyrene and indine[1,2,3-cd]pyrene were 5.91%, 6.08%, 6.51%, 6.46%, and 4.21%, respectively. Conclusions Short-term exposure to PAHs in PM_2.5, including fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene and indine[1,2,3-cd]pyrene, was significantly associated with an increased risk of mortality among residents.

Objective To analyzing the correlation between serum microRNA(miRNA,miR)-128-3p,miRNA(miR)-126 expression and Gensini score in patients with coronary artery disease.Methods A retrospective study was conducted on 60 patients with coronary artery disease who were treated in the Department of Cardiology,Harrison International Peace Hospital from June 2020 to 2022.They were selected as the observation group,and another 60 patients with non-coronary artery disease who were treated in the hospital during the same period were selected as the control group.Serum miR-128-3p,miR-126 and Gensini scores were measured and compared between the two groups,and compared the serum miR-128-3p,miR-126 and Gensini scores of patients with single,double,and multiple vessel lesions in the observation group.According to the stenosis rate of coronary arteries,they were divided into I degree,II degree,III degree and IV degree groups.The serum miR-128-3p,miR-126 and Gensini scores were compared among different stenosis grading groups.According to the Gensini score,patients were divided into mild and severe lesion groups.According to the Gensini score,patients were divided into mild and severe lesion groups.The serum miR-128-3p and miR-126 levels were compared between the mild and severe lesion groups.Pearson analysis determined the correlation between serum miR-128-3p and miR-126 levels and Gensini score.Receiver operating characteristic curve(ROC)was plotted,and the area under curve(AUC)was calculated to analyze the predictive efficacy of the combined detection of serum miR-128-3p and miR-126 levels for coronary artery disease.Logistic regression analysis of influencing factors of coronary artery disease.Results Compared with the control group,the observation group showed an increase in serum miR-128-3p(4.28±0.52 vs 2.61±0.36)and Gensini score(31.29±5.62 score vs 6.16±1.04 score),observation group showed a decrease in serum miR-126,with statistically significant differences(t=21.678,34.058,11.002,all P<0.05).Compared with the double vessel disease and single vessel disease groups,the serum miR-128-3p and Gensini score in the multi vessel disease group increased(t=4.945,7.171;6.795,11.686),the serum miR-126 decreased(t=3.104,5.033),and the differences were statistically significant(all P<0.05).Compared with the I～II group,the serum miR-128-3p and Gensini score in the III～IV group increased significantly(t=5.590,12.961),the serum miR-126 decreased significantly(t=6.021),with statistical significance differences(all P<0.05).Compared with the mild lesion group,the serum miR-128-3p level increased in the severe lesion group(t=4.056),the serum miR-126 level decreased(t=4.806),and the differences were statistically significant differences(all P<0.05).There was a positive correlation between serum miR-128-3p and Gensini score(r=0.404,P<0.05),and a negative correlation between serum miR-126 and Gensini score(r=-0.393,P<0.05).The AUC of combined detection of serum miR-128-3p and miR-126 was higher than that of single detection,and the differences were statistically significant(Z=2.768,2.152,all P<0.05).The differences in smoking,triglycerides(TG),uric acid(UA),fibrinogen(FIB)between the observation group and the control group were statistically significant(t/χ2=4.231～28.732,all P<0.05).Conclusion Patients with coronary artery disease have high expression of serum miR-128-3p and low expression of serum miR-126,which is correlated with Gensini score.The combined detection of serum miR-128-3p and miR-126 can improve the predictive efficiency of coronary artery disease,and the occurrence of coronary artery disease is related to multiple factors,which should be given clinical attention.

Objective:To explore the molecular mechanism by which the methionine adenosyltransferase 2A (MAT2A)/β-catenin/zinc finger E-box binding homeobox 1 (ZEB1)/epithelial-mesenchymal transition (EMT) pathway regulates neural tube defect (NTD) through intracellular S-adenosylmethionine (SAM).Methods:A mouse NTD model was induced using the SAM metabolic disorder inhibitor ethionine. Eighty specific pathogen-free C57BL/6 mice were divided into three groups: a normal group (36 mice), an ethionine group (46 mice), and an ethionine+SAM group (44 mice). Phosphate-buffered saline (PBS), ethionine, and ethionine+SAM were respectively injected intraperitoneally on embryonic day 7.5 (E7.5), and the mice were sacrificed on E10.5. Embryonic tissues were collected, and the morphology of embryos in each group was observed under a stereomicroscope. The interaction between ethionine and MAT2A was analyzed using Autodock software. The expression levels of MAT2A, β-catenin, ZEB1, and EMT-related proteins in the brain tissues of embryos from the three groups were measured using immunofluorescence, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (RT-qPCR). Variance analysis was used for intergroup comparisons.Results:(1) Autodock analysis results showed that MAT2A binds to ethionine through covalent bonds, exhibiting a complementary effect, thereby accelerating the expression of MAT2A. (2) After successful construction of the NTD model, normal embryos were plump with well-developed brains. NTD embryos showed delayed development, obvious anencephaly, unclosed neural tubes, and asymmetry. (3) The levels of SAM and SAH in the embryonic tissues of the ethionine group were significantly lower than those in the normal group (1 737.56±95.64 vs. 872.33±205.11, and 89.17±9.50 vs. 51.25±9.48, respectively). The SAM and SAH levels in the ethionine+SAM group was 1 197.00±222.27 and 66.61±12.25, significantly higher than those in the ethionine group ( P<0.017). Compared with the normal group and the ethionine+SAM group, the expression of MAT2A mRNA in the embryonic brain tissue of the ethionine group was significantly upregulated (1.00±0.00, 1.59±0.52, and 2.42±0.53, respectively, F=49.64, P<0.001; pairwise comparisons between groups P<0.017). (4) Compared with the normal group, the expression of Ctnnb1 in the ethionine group was reduced, and the expression of Ctnnb1 in the ethionine+SAM group was higher than that in the ethionine group (1.00±0.00, 0.38±0.16, and 0.76±0.10, respectively, F=149.03, P<0.001; pairwise comparisons between groups P<0.017). (5) The expression of ZEB1 in the ethionine group was higher than that in the normal group and the ethionine+SAM group (2.91±0.55, 1.00±0.00, and 1.61±0.20, respectively, F=150.01, P<0.001; pairwise comparisons between groups P<0.017). (6) The expression levels of E-cadherin and Vimentin in the ethionine group were lower than those in the normal group. In contrast, the expression of N-cadherin was higher than that in the normal group. After SAM supplementation, the expression levels of E-cadherin and Vimentin were upregulated, and the expression level of N-cadherin was downregulated (0.54±0.12, 1.00±0.00, and 0.72±0.14, respectively, F=87.44; 0.53±0.17, 1.00±0.00, and 0.76±0.09, F=87.44; 3.11±0.53, 1.00±0.00, and 2.13±0.56, F=95.54; all P<0.001; pairwise comparisons within the same index group P<0.017]). Conclusions:Ethionine promotes the expression of MAT2A, leading to reduced SAM production. Ethionine regulates the level of ZEB1 by increasing MAT2A and inhibits the EMT process to interfere with methionine cycle metabolism, ultimately resulting in NTD.

Objective To analyzing the correlation between serum microRNA(miRNA,miR)-128-3p,miRNA(miR)-126 expression and Gensini score in patients with coronary artery disease.Methods A retrospective study was conducted on 60 patients with coronary artery disease who were treated in the Department of Cardiology,Harrison International Peace Hospital from June 2020 to 2022.They were selected as the observation group,and another 60 patients with non-coronary artery disease who were treated in the hospital during the same period were selected as the control group.Serum miR-128-3p,miR-126 and Gensini scores were measured and compared between the two groups,and compared the serum miR-128-3p,miR-126 and Gensini scores of patients with single,double,and multiple vessel lesions in the observation group.According to the stenosis rate of coronary arteries,they were divided into I degree,II degree,III degree and IV degree groups.The serum miR-128-3p,miR-126 and Gensini scores were compared among different stenosis grading groups.According to the Gensini score,patients were divided into mild and severe lesion groups.According to the Gensini score,patients were divided into mild and severe lesion groups.The serum miR-128-3p and miR-126 levels were compared between the mild and severe lesion groups.Pearson analysis determined the correlation between serum miR-128-3p and miR-126 levels and Gensini score.Receiver operating characteristic curve(ROC)was plotted,and the area under curve(AUC)was calculated to analyze the predictive efficacy of the combined detection of serum miR-128-3p and miR-126 levels for coronary artery disease.Logistic regression analysis of influencing factors of coronary artery disease.Results Compared with the control group,the observation group showed an increase in serum miR-128-3p(4.28±0.52 vs 2.61±0.36)and Gensini score(31.29±5.62 score vs 6.16±1.04 score),observation group showed a decrease in serum miR-126,with statistically significant differences(t=21.678,34.058,11.002,all P<0.05).Compared with the double vessel disease and single vessel disease groups,the serum miR-128-3p and Gensini score in the multi vessel disease group increased(t=4.945,7.171;6.795,11.686),the serum miR-126 decreased(t=3.104,5.033),and the differences were statistically significant(all P<0.05).Compared with the I～II group,the serum miR-128-3p and Gensini score in the III～IV group increased significantly(t=5.590,12.961),the serum miR-126 decreased significantly(t=6.021),with statistical significance differences(all P<0.05).Compared with the mild lesion group,the serum miR-128-3p level increased in the severe lesion group(t=4.056),the serum miR-126 level decreased(t=4.806),and the differences were statistically significant differences(all P<0.05).There was a positive correlation between serum miR-128-3p and Gensini score(r=0.404,P<0.05),and a negative correlation between serum miR-126 and Gensini score(r=-0.393,P<0.05).The AUC of combined detection of serum miR-128-3p and miR-126 was higher than that of single detection,and the differences were statistically significant(Z=2.768,2.152,all P<0.05).The differences in smoking,triglycerides(TG),uric acid(UA),fibrinogen(FIB)between the observation group and the control group were statistically significant(t/χ2=4.231～28.732,all P<0.05).Conclusion Patients with coronary artery disease have high expression of serum miR-128-3p and low expression of serum miR-126,which is correlated with Gensini score.The combined detection of serum miR-128-3p and miR-126 can improve the predictive efficiency of coronary artery disease,and the occurrence of coronary artery disease is related to multiple factors,which should be given clinical attention.

Objective:To retrospectively summarize the clinical characteristics and treatment of 49 patients with hyperthyroid cardiopath and to explore the diagnosis and treatment methods of hyperthyroid cardiopathy.Methods:A total of 49 patients with hyperthyroid cardiopath(HC group) who were successfully treated and followed up in the Department of Endocrinology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, from January 2016 to December 2021 were collected, and 85 cases of Graves′ disease without heart disease were collected as the control group(GD group). The medical history, laboratory tests, and echocardiographic parameters of the two groups were compared. Differences in thyroid and cardiac indicators before and after treatment in the HC group were summarized, along with the dosage of β-receptor blockers used in treating different types of conditions(atrial fibrillation and heart failure.Results:Patients in the HC group were older and had a longer duration of hyperthyroidism than those in the GD group( P<0.001, P=0.002). There were no significant differences in thyroid hormone levels between the two groups except for reverse triiodothyronine(rT 3). Age and rT 3 were independent risk factors of hyperthyroid cardiopathy. rT 3 level was linearly positively correlated with brain natriuretic peptide, systolic pulmonary artery pressure, left artrium diamete (LAD) and left ventricular end-systolic diameter(LVDs; r=0.352, P<0.001; r=0.392, P=0.019; r=0.202, P=0.029; r=0.242, P=0.028). In patients of HC group, free triiodothyronine(FT 3) level returned to normal range after 2.87(1.63, 5.53) months of treatment with radioiodine(41/49) or antithyroid drugs(8/49), while brain natriuretic peptide, LAD, LVDs, and systolic pulmonary artery pressure declined after 5.00(1.25, 8.00) months of treatment. Non-selective β-receptor blockers were used for both hyperthyroid heart failure and atrial fibrillation, and there was no statistically significant difference in dosage[(86.52±47.83)mg vs(88.67±47.19)mg, P>0.05]. Conclusions:rT 3 may be a biomarker of hyperthyroid cardiopath and indicate the severity of hyperthyroidism. β-receptor blockers are crucial in treating patients with hyperthyroidism who develop atrial fibrillation and heart failure.

Objective:To establish the reference for serum metabolomics profiles among healthy Han adults in China, and explore the variation on metabolomics profiles by geographic regions, sex, and age.Methods:Cross-sectional data and serum samples were obtained from the China National Health Survey. A total of 1 039 male and 1 032 female healthy adults(≥30 years) were included in this study. Serum metabolomics analyses were conducted with ultra-performance liquid chromatography-mass spectrometry(UPLC-MS). Orthogonal partial least squares discriminant analysis(OPLS-DA) was performed to compare the differences of metabolomics among different region, sex, and age.Results:Significant differences on metabolomics profiles were identified among region, sex, and age. A total of 114 region-related metabolites were spotted, including 53 metabolites that involved in human metabolic pathways, mainly peptides(20 metabolites) and glycerophospholipid metabolism-related(14 metabolites). Fifty-nine metabolites were pinned down to be sex-related, among which cotinine was significant in all 7 provinces. Age-related metabolites were only found in Shaanxi and Hainan, with 22 metabolites were recognized.Conclusion:Serum metabolomics varies by geographic regions, sex, and age. When metabolomics is applied for diagnosis or biomarker screening in various studies, it shall take into consideration of setting tailored references.

Objective:To study the clinical significance of early detection of soluble growth stimulating gene 2 protein (sST2) and prealbumin (PAB) in patients with chronic pulmonary heart disease (CPHD) complicated with refractory heart failure.Methods:From September 2017 to June 2019, 112 CPHD patients complicated with refractory heart failure were admitted to Hengshui People's Hospital. The selected patients met the revised guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease (2013 revision) and the cardiac function grade Ⅲ-Ⅳ according to the grading criteria of the New York Cardiology Society. Cardiogenic shock, severe liver and kidney dysfunction, malignant tumors, anemia, and autoimmune diseases were excluded. Patients were divided into the high PAB group (≥200 mg/L) and the low PAB group (<200 mg/L) according to the PAB level on admission. The pulmonary artery systolic blood pressure (PASP), pulmonary artery mean pressure (MPAP), and left ventricular ejection fraction (LVEF) were observed in the two groups before and after the treatment. PAB, total bilirubin (TBIL), hypersensitive C reactive protein (hs-CPR), N-terminal B type brain natriuretic peptide (NT-proBNP) and sST2 levels were detected. Measurement data were expressed in terms of mean ± standard deviation, the counting data were compared using χ 2 test. Correlation analysis was conducted using Spearman correlation test. Results:There were 40 cases in the high PAB group and 72 cases in the low PAB group. There were no statistically significant differences in general data between the high PAB and low PAB groups ( P>0.05). Hospitalization time was significantly different between the two groups ( P<0.05). Before the treatment, there were no significant differences in PASP, MPAP, NT-proBNP and LVEF between the two groups ( P>0.05). High sST2 was significantly different between the two groups ( P<0.05). After the treatment, PASP, MPAP, NT-proBNP and sST2 were decreased in both groups, and the improvement was more obvious in the high PAB group than in the low PAB group, with statistical significance ( P<0.05). Before the treatment, the levels of TBIL and hs-CPR were not statistically different between the high PAB and low PAB groups ( P>0.05). However, the levels of TBIL and hs-CPR were beyond the normal range. After the treatment, TBIL and hs-CPR were decreased in both groups, and there was statistically significant difference between the two groups ( P<0.05). Spearman correlation analysis showed that PAB was negatively correlated with sST2 ( r=-0.778, P=0.001). There was a positive correlation between cardiac function and sST2 ( r=0.569, P=0.034), hospitalization time ( r=0.572, P=0.033) in patients with refractory heart failure. The higher the sST2 of CPHD with refractory heart failure, the longer the patient hospitalization time, and the more serious the heart failure was. The area under the combined ROC curve of PAB and sST2 was 0.756. CPHD patients with refractory heart failure had the greatest predictive value. Conclusion:The combined test of sST2 and PAB can evaluate the condition and outcome of CPHD patients with refractory heart failure, and guide the clinic.

Objective:To investigate the high resolution CT (HRCT) features of COVID-19 in children.Methods:A retrospective analysis was performed on the chest HRCT findings of 22 children who were diagnosed as COVID-19 by clinical and nucleic acid testing in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 25 to February 5, 2020. There were 12 boys and 10 girls, aged from 2 months to 14 years old, with a median age of 4 years, and 14 patients were under 5 years old. The characteristics of lung lesions on HRCT such as distribution, shape, density and so on and whether there were hilar and mediastinal lymph node enlargement and pleural changes were evaluated by 2 radiologists.Results:In all of the 22 patients, the chest CT manifestations were normal in 3 patients (3/22) , meanwhile the lung involvement of the lesion was found in 19 patients (19/22). Among them, 7 patients had unilateral lung involvement, and 12 patients had bilateral involvement. The HRCT manifestations were as follows. The HRCT showed the ground glass opacity (GGO) in 6 patients, including 4 cases with light opacity and 2 with typical crazy paving sign. Four patients had lung consolidation, with local fibrous stripes and patchy hyperdensity. Six patients had mixed GGO, including 1 case with right white lung. The bronchopneumonia-like changes were seen in 3 cases with scattered spot-like or mixed patchy. The lesions in the lower lobe were more serious than those in the upper lobe, and the lesions in the lateroposterior zone of the lung were more common than those in the apical and central area of the lung. No enlarged lymph nodes and pleural effusion were seen in all patients, but 1 case had thickened interlobar pleura.Conclusions:The HRCT manifestations of COVID-19 in children are varied, and the comprehensive assessment need to be made in combination with epidemiological data, clinical manifestations and laboratory tests. However, the chest HRCT plays an important role in early diagnosis, prevention and management of COVID-19.

Objective:To explore the association between socioeconomic status (SES) and overweight/obesity in Yi people in Sichuan province.Methods:A cross-sectional study was conducted in Liangshan Yi Autonomous Prefecture in 2015. Stratified cluster sampling method was used to enroll Yi farmers and rural-to-urban Yi migrants aged 20-80 years. SES was measured by education level, personal annual income, and compound SES index. Unconditional logistic regression models were used to determine the association between SES and overweight/obesity (BMI≥24.0 kg/m 2). Results:1 894 Yi farmers and 1 162 rural-to urban migrants were included in the analysis. After adjustment for age, smoking, drinking and physical activity, compared with illiteracy, OR for farmer males with higher education level (primary or junior school, senior high school or higher) were 1.71 (95 %CI: 1.13-2.58) and 4.15 (95 %CI: 2.10-8.22). Compared with lower income group (<5 000 CNY/y), the higher income group had increased risk ( OR=1.66, 95 %CI: 1.12-2.44). For farmer males with medium and high SES level, the risk of overweight/obesity were 1.65 (95 %CI: 1.02-2.67) and 3.26 (95 %CI: 1.97-5.42) compared with low level of SES. For farmer females, the risk increased with the higher income, with OR as 1.49 (95 %CI: 1.10-2.02). Compared with low SES level, farmer females with medium level of SES was associated with 1.47 (95 %CI: 1.11-1.95) times higher risk of overweight/obesity. In Yi migrants, the association between SES and overweight/obesity was not found. Conclusion:Socioeconomic status was positively associated with overweight/obesity only in Yi farmers.