Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Macrophages are widely distributed immune cells that contribute to tissue homeostasis. Human THP-1 cells have been widely used in various macrophage-associated studies, especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, the molecular characterization of four M2 subtypes (M2a, M2b, M2c, and M2d) derived from THP-1 has not been fully investigated. In this study, we systematically analyzed the protein expression profiles of human THP-1-derived macrophages (M0, M1, M2a, M2b, M2c, and M2d) using quantitative proteomics approaches. The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated. The results showed that M2a and M2b, and M2c and M2d have very similar protein expression profiles. These data could serve as an important resource for studies of macrophages using THP-1 cells, and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research.
Humans ; Macrophages/metabolism* ; Phenotype ; Proteomics ; THP-1 Cells

Objective:This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China.Methods:Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods.Results:A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes ( P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk ( OR=0.84, 95% CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA ( P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance ( P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion:The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.

Objective: To investigate the relationship between maternal disease in early pregnancy of women of childbearing age and congenital heart disease of neonates. Methods: A cross-sectional design was used in this study and stratified multistage random sampling method was used. A questionnaire survey was conducted in the childbearing-aged women during 2010-2013 in Shaanxi province. Propensity score (PS) matched (1∶1) analysis was used to match participants with diseases to those without disease in early pregnancy. Through the control of the confounders step by step, a logistic regression model was established to evaluate the ORs of congenital heart disease according to the independent variable of maternal disease. Results: A total of 28 680 pairs of mothers and infants were included in this study, the proportion of the women with disease in early pregnancy was 20.25% (5 807). After PS matching, 5 436 pairs were matched. After adjusting all confounding factors, the multivariable logistic regression analysis results showed that maternal disease (OR=1.86, 95%CI: 1.23-2.81), especially cold (OR=2.19, 95%CI: 1.46-3.28), gynecological disease (OR=4.74, 95%CI: 2.03-11.09) and diabetes (OR=14.00, 95%CI: 1.64-119.21), in early pregnancy were the risk factors for congenital heart disease of neonate. Conclusion In women of childbearing age, disease in early pregnancy, especially cold, gynecological disease and diabetes, can increase the risk of congenital heart disease in neonates.

Objective: To investigate the interaction of pregnancy-induced hypertension and history of preterm birth on the risk of small for gestational age. Methods: Stratified multistage random sampling method was used to choose samples from 30 districts and counties of Shaanxi province. Information on childbearing-age women with their children between January 2010 and November 2013 was retrospectively collected through face-to-face questionnaire survey. The childbearing-aged women were in pregnancy or having had definite outcomes of pregnancy. Enumeration data were described by percentage, and measurement data were described by Mean±SD, and χ² test was used to compare the rates. Unconditional logistic regression analysis was performed to estimate the interaction between pregnancy-induced hypertension and history of preterm birth on the risk of small for gestational age, and by using small for gestational age as dependent variables, pregnancy-induced hypertension and history of preterm birth as independent variables. Confounding factors were under control. Firstly, the association between pregnancy-induced hypertension and small for gestational age has been analyzed in primiparas, secondly, interaction of pregnancy-induced hypertension and history of preterm birth on the risk of small for gestational age has been analyzed in multiparas. Results: A total of 25 751 women of childbearing age and their children were recruited. 60.55% (15 592/25 751) were primiparas, 39.45% (10 159/25 751) were multiparas, the rate of history of preterm birth was 1.89% (192/10 159) for multiparas. The incidence rates of pregnancy-induced hypertension and small for gestational age were 1.55% and 15.49% in pregnant woman (400/25 751) and their newborns (3 990/25 751). Unconditioned logistic regression analysis showed that compared with woman without pregnancy-induced hypertension, primiparas with pregnancy-induced hypertension had increased risk of small for gestational age (OR=1.43, 95%CI: 1.02-2.00, P=0.041). Regarding multiparas, the main effect of pregnancy-induced hypertension had a positive correlation with small for gestational age (OR=1.34, 95%CI: 0.91-1.96), but there was no statistical significance (P=0.138). The main effect of history of preterm birth was positively correlated with small for gestational age (OR=1.61, 95%CI: 1.13-2.31, P=0.009). The interaction term "pregnancy-induced hypertension×history of preterm birth" was positively associated with risk of small for gestational age (OR=5.93, 95%CI: 1.19-29.61, P=0.030). Conclusions Pregnancy-induced hypertension was associated with increased risk for small for gestational age in both primiparas and multiparas, and history of preterm birth further increased risk for small for gestational age in pregnant women with pregnancy-induced hypertension, indicating that there was multiplication interaction between pregnancy-induced hypertension and history of preterm birth.

Objective To explore the relationship of four kinds of lifestyle factors,namely,prenatal passive smoking,hair dyeing or perming,exposure to noise,living in a house renovated in the past one year,with congenital heart disease.Methods A hospital-based case-control study was conducted.Totally 270 mothers in the case group and 1633 mothers in the control group were interviewed through a face-to-face questionnaire survey.A generalized linear model was employed to investigate the association between congenital heart disease and prenatal lifestyle factors.Results Both in Model 1 and Model 2,prenatal hair dyeing or perming had no association with congenital heart disease.On the other hand,prenatal passive smoking,exposure to noise and living in a house renovated in the past one year all increased the risk of congenital heart disease.After adjustment for all confounders,the OR values were 1.771 (95％ CI:1.079-2.909),2.079 (95％ CI:1.310-3.298),and 2.494 (95％ CI:1.511-4.116),respectively.Conclusion Prenatal passive smoking,exposure to noise and living in a house renovated in the past one year are the risk factors for congenital heart disease.It is very important to avoid such factors during pre-pregnancy and pregnancy.

Objective To explore the association between exposure to ambient air pollution during pregnancy and congenital heart disease so as to provide evidence for primary prevention of congenital heart disease.Methods Epidemiologic studies on ambient air pollution and congenital heart diseases were reviewed.Summary risk estimates were calculated at high versus low exposure levels and risk per-unit-increase in continuous pollutant concentration.Meta-analysis was conducted with Stata 12.0 software.Results A total of 20 articles in English were qualified for inclusion.Results from Meta-analysis showed that CO exposures were related to the increase on the risk of tetralogy of fallot (high versus low exposure level OR=1.22,95％CI:1.03-1.44),while the exposures to NO2 were related to the increase on risk of coarctation of aorta (per 10 mm3/m3 OR=1.01,95％CI:1.01-1.20).Exposures to O3 were related to the increase on risk of atrial septal defect (per 10 mm3/m3 OR=1.14,95％CI:1.03-1.26),and PM10 exposures were related to the increase on risk of atrial septal defect (per 10 μg/m3 OR=1.10,95％CI:1.03-1.19).In addition,there were inverse associations between CO and atrial septal defect and between PM10 and ventricular septal defect.Conclusion Exposures to CO,NO2,O3,PM10 during pregnancy seemed to be associated with congenital heart diseases.

Objective To investigate the effect of folic acid supplementation in childbearing aged women during pregnancy on the birth weight of newborns in Shaanxi province.Methods A questionnaire survey was conducted among the childbearing aged women selected through multistage stratified random sampling in Shaanxi during 2010-2013,all of these childbearing aged women were in pregnancy or had definite pregnancy outcomes.The birth weight of newborns and folic acid supplementation during pregnancy were used as the dependent variables and independent variables respectively in multiple linear regression model and quantile regression model and confounding factors were controlled.Results Multiple linear regression analysis showed that the birth weight of newborns whose mothers had folic acid supplementation during pregnancy were significantly higher than those whose mothers had no folic acid supplementation during pregnancy,an average increase of 29.56 g (B=29.56,t=4.69 and P＜0.01).Quantile regression analysis showed from very low to higher percentiles (q=0-0.55,q=0.65,q=0.75-0.80),the birth weights of newborns whose mothers supplemented folic acid were higher than those whose mother did not supplement folic acid,the difference was significant,but the increase varied.As the increase of the percentiles of birth weight,the body weight increase declined gradually in those whose mothers had folic acid supplementation compared with those whose mothers had no folic acid supplementation.Conclusion Folic acid supplementation during pregnancy can increase the birth weight of newborns,the influence was greater in newborns with lower body weight than in newborns with higher body weight.