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.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Objective:To investigate the prevalence of dysphagia in community-dwelling elderly patients with chronic dis-eases and to analyze the correlation between the categories of chronic diseases and the prevalence of dysphagia.Method:Elderly people(aged ≥60 years)with one of five common chronic diseases(hypertension,diabetes,coronary heart disease,respiratory diseases,and hepatobiliary diseases)were recruited from Shipai Community health service center of Tianhe District.Eating assessment tool-10 and Water Swallow Test were used to evalu-ate swallowing function.Age-adjusted Charlson comorbidity index(ACCI)classification,grip strength test and 4-meter walking test were used to evaluate physical endurance of patients.The prevalence of dysphagia was de-termined among individuals with these chronic diseases and varying degrees of multimorbidity.The correlation between dysphagia and gender,age,chronic diseases,grip strength and walking endurance was analyzed.Result:The total number of respondents was 2352,of which 2121 were effectively surveyed.Among them,252 cases were positive for dysphagia,and the prevalence of dysphagia was 11.88％.The prevalence of dys-phagia was 63.89％for hypertension,28.57％for diabetes,39.68％for coronary heart disease,8.73％for respi-ratory diseases,and 2.78％for hepatobiliary diseases.There was no statistically significant difference in the cor-relation between gender,age and grip strength and dysphagia.Univariate regression analysis showed that respi-ratory diseases(t=3.987,P＜0.001),hepatobiliary diseases(t=2.158,P＜0.05),ACCI(t=2.745,P＜0.05),4-meter walk test(t=7.082,P＜0.001),the results were statistically significant(P＜0.05).Conclusion:Dysphagia is highly prevalent among elderly individuals with chronic diseases in the community.Respiratory diseases,hepatobiliary diseases,ACCI score,and 4m walk test are positively correlated with the prevalence of dysphagia.

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.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Objective:To investigate the prevalence of dysphagia in community-dwelling elderly patients with chronic dis-eases and to analyze the correlation between the categories of chronic diseases and the prevalence of dysphagia.Method:Elderly people(aged ≥60 years)with one of five common chronic diseases(hypertension,diabetes,coronary heart disease,respiratory diseases,and hepatobiliary diseases)were recruited from Shipai Community health service center of Tianhe District.Eating assessment tool-10 and Water Swallow Test were used to evalu-ate swallowing function.Age-adjusted Charlson comorbidity index(ACCI)classification,grip strength test and 4-meter walking test were used to evaluate physical endurance of patients.The prevalence of dysphagia was de-termined among individuals with these chronic diseases and varying degrees of multimorbidity.The correlation between dysphagia and gender,age,chronic diseases,grip strength and walking endurance was analyzed.Result:The total number of respondents was 2352,of which 2121 were effectively surveyed.Among them,252 cases were positive for dysphagia,and the prevalence of dysphagia was 11.88％.The prevalence of dys-phagia was 63.89％for hypertension,28.57％for diabetes,39.68％for coronary heart disease,8.73％for respi-ratory diseases,and 2.78％for hepatobiliary diseases.There was no statistically significant difference in the cor-relation between gender,age and grip strength and dysphagia.Univariate regression analysis showed that respi-ratory diseases(t=3.987,P＜0.001),hepatobiliary diseases(t=2.158,P＜0.05),ACCI(t=2.745,P＜0.05),4-meter walk test(t=7.082,P＜0.001),the results were statistically significant(P＜0.05).Conclusion:Dysphagia is highly prevalent among elderly individuals with chronic diseases in the community.Respiratory diseases,hepatobiliary diseases,ACCI score,and 4m walk test are positively correlated with the prevalence of dysphagia.

Objectives:A two-sample,multivariable,bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal relationships between serum micronutrients (including vitamin A,vitamin B6,vitamin B9,vitamin B12,vitamin C,vitamin D,vitamin E,copper,iron,selenium,zinc,calcium,magnesium,and potassium) and coronary atherosclerosis (CA).Methods:Publicly available data from genome-wide association studies in European populations were analyzed,14 serum micronutrients were used as exposure factors and single nucleotide polymorphisms (SNPs) were used as instrumental variables,outcome was defined as CA.A two-sample MR analysis was performed using inverse variance weighted (IVW) method,MR-Egger regression,weighted median estimator (WME),simple model,and weighted model to assess the relationship between each micronutrient and CA.Multivariable MR analysis was used to evaluate the independent impacts of single exposure factors on CA,reverse MR was applied to assess the potential for reverse causality.Sensitivity analysis was conducted using Cochran's Q test,MR-Egger regression,MR-PRESSO,and leave-one-out analysis to evaluate the robustness of the results.Results:The univariable two-sample MR study evidenced the significant associations between serum levels of vitamin A (IVW:OR=0.019,95％CI:0.001-0.451,P=0.014),vitamin B12 (IVW:OR=1.221,95％CI:1.015-1.469,P=0.034),copper (IVW:OR=1.023,95％CI:1.003-1.044,P=0.026),and potassium (IVW:OR=0.837,95％CI:0.714-0.980,P=0.027) with the risk of CA.After adjustment using multivariable MR analysis,independent causal effects on CA were observed for serum levels of vitamin A (IVW:OR=0.016,95％CI:0.001-0.214,P=0.002) and copper (IVW:OR=1.029,95％CI:1.002-1.056,P=0.036).Reverse MR analysis observed a reverse causal relationship between CA risk and serum vitamin A level,though the effect was minimal (IVW:OR=0.999),while no reverse causality was found between CA risk and serum copper level.There was no evidence to support a causal relationship between the remaining serum micronutrients and CA.These findings were robust through extensive sensitivity analyses.Conclusions:The levels of serum vitamin A and copper may relate to the susceptibility of CA in the studied population.

Objective To explore the health promotion behaviors among patients with pulmonary tuberculosis(TB),and to analyze its relationship with health locus of control,in order to provide scientific references for improving TB patients'health-promotion behaviors in clinical nursing care.Methods The interpretive sequence mixed method design was utilized.A convenient sampling was used to enroll 300 TB patients from 2 TB specialized tertiary hospitals in Xi'an as research subjects from January to April 2023.General information questionnaire,Health promoting lifestyle profile-Ⅱ,and Multidimensional health locus of control scale were used to collect data,and single-factor analysis and multiple linear regression analysis were conducted.Purposeful sampling was used to select 11 TB patients for a semi-structured interview,and the Colaizzi 7-step method was used to extract themes.Results In the quantitative study,the total score of health promoting behaviors in 294 TB patients was(110.26±15.74).Patients'intemal health locus of control,chance health locus of control,and occupational status significantly influenced their health-promotion behaviors(P＜0.05).In the qualitative study,4 themes were extracted,including awakening self-awareness of health,the desire to establish a normal life,the distress of multiple uncertainties,and the immediate effect of authoritative guidance.The qualitative and quantitative studies complemented each other and further verified the relationship between health promotion behaviors and health locus of control of TB patients.Conclusion The level of health-promotion behaviors in TB patients needs to be further improved.Nurses need to take systematic health education as an opportunity by the catalytic effect of individual health awareness,to improve their internal locus of control,reduce their opportunity control tendency due to multiple uncertainties,with the ultimate purpose of helping TB patients form and maintain health promotion behaviors.

Objectives:A two-sample,multivariable,bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal relationships between serum micronutrients (including vitamin A,vitamin B6,vitamin B9,vitamin B12,vitamin C,vitamin D,vitamin E,copper,iron,selenium,zinc,calcium,magnesium,and potassium) and coronary atherosclerosis (CA).Methods:Publicly available data from genome-wide association studies in European populations were analyzed,14 serum micronutrients were used as exposure factors and single nucleotide polymorphisms (SNPs) were used as instrumental variables,outcome was defined as CA.A two-sample MR analysis was performed using inverse variance weighted (IVW) method,MR-Egger regression,weighted median estimator (WME),simple model,and weighted model to assess the relationship between each micronutrient and CA.Multivariable MR analysis was used to evaluate the independent impacts of single exposure factors on CA,reverse MR was applied to assess the potential for reverse causality.Sensitivity analysis was conducted using Cochran's Q test,MR-Egger regression,MR-PRESSO,and leave-one-out analysis to evaluate the robustness of the results.Results:The univariable two-sample MR study evidenced the significant associations between serum levels of vitamin A (IVW:OR=0.019,95％CI:0.001-0.451,P=0.014),vitamin B12 (IVW:OR=1.221,95％CI:1.015-1.469,P=0.034),copper (IVW:OR=1.023,95％CI:1.003-1.044,P=0.026),and potassium (IVW:OR=0.837,95％CI:0.714-0.980,P=0.027) with the risk of CA.After adjustment using multivariable MR analysis,independent causal effects on CA were observed for serum levels of vitamin A (IVW:OR=0.016,95％CI:0.001-0.214,P=0.002) and copper (IVW:OR=1.029,95％CI:1.002-1.056,P=0.036).Reverse MR analysis observed a reverse causal relationship between CA risk and serum vitamin A level,though the effect was minimal (IVW:OR=0.999),while no reverse causality was found between CA risk and serum copper level.There was no evidence to support a causal relationship between the remaining serum micronutrients and CA.These findings were robust through extensive sensitivity analyses.Conclusions:The levels of serum vitamin A and copper may relate to the susceptibility of CA in the studied population.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.