Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway.

OBJECTIVE: To explore the anti-tumor effect of safflower yellow (SY) against hepatocellular carcinoma (HCC) and the underlying potential mechanism. METHODS: An in vitro model was established by mixing Luc-Hepa1-6 cells and CD3+CD8+ T cells, followed by adding programmed cell death protein 1 (PD-1) antibody (Anti-mPD-1) with or without SY. The apoptosis was detected by flow cytometry and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The protein levels of programmed cell death 1 ligand 1 (PD-L1), chemokine ligand (CCL5), C-X-C motif chemokine ligand 10 (CXCL10) were measured by Western blot. An in situ animal model was established in mice followed by treatment with anti-mPD-1 with or without SY. Bioluminescence imaging was monitored with an AniView 100 imaging system. To establish the FAK-overexpressed Luc-Hepa1-6 cells, cells were transfected with adenovirus containing pcDNA3.1-FAK for 48 h. RESULTS: The fluorescence intensity, apoptotic rate, release of inflammatory cytokines, and CCL5/CXCL10 secretion were dramatically facilitated by anti-mPD-1 (P<0.01), accompanied by an inactivation of PD-1/PD-L1 axis, which were extremely further enhanced by SY (P<0.05 or P<0.01). Increased fluorescence intensity, elevated percentage of CD3+CD8+ T cells, facilitated release of inflammatory cytokines, inactivated PD-1/PD-L1 axis, and increased CCL5/CXCL10 secretion were observed in Anti-mPD-1 treated mice (P<0.01), which were markedly enhanced by SY (P<0.05 or P<0.01). Furthermore, the enhanced effects of SY on inhibiting tumor cell growth, facilitating apoptosis and inflammatory cytokine releasing, suppressing the PD-1/PD-L1 axis, and inducing the CCL5/CXCL10 secretion in Anti-mPD-1 treated mixture of Luc-Hepa1-6 cells and CD3+CD8+ T cells were abolished by FAK overexpression (P<0.01). CONCLUSION: SY inhibited the progression of HCC by mediating immunological tolerance through inhibiting FAK.

The role of PD-1 signaling in health and immune-related diseases.

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.

The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis.

The epithelial lining of the stomach undergoes rapid turnover to preserve its structural and functional integrity, a process driven by long-lived stem cells residing in the antral and corpus glands. Several subpopulations of gastric stem cells have been identified and their phenotypic and functional diversities linked to spatiotemporal specification of stem cells niches. Here, we review the biological features of gastric stem cells at various locations of the stomach under homeostatic conditions, as demonstrated by reporter mice, lineage tracing, and single cell sequencing. We also review the role of gastric stem cells in epithelial regeneration in response to injury. Moreover, we discuss emerging evidence demonstrating that accumulation of oncogenic drivers or alteration of stemness signaling pathways in gastric stem cells promotes gastric cancer. Given a fundamental role of the microenvironment, this review highlights the role reprogramming of niche components and signaling pathways under pathological conditions in dictating stem cell fate. Several outstanding issues are raised, such as the relevance of stem cell heterogeneity and plasticity, and epigenetic regulatory mechanisms, to Helicobacter pylori infection-initiated metaplasia-carcinogenesis cascades. With the development of spatiotemporal genomics, transcriptomics, and proteomics, as well as multiplexed screening and tracing approaches, we anticipate that more precise definition and characterization of gastric stem cells, and the crosstalk with their niche will be delineated in the near future. Rational exploitation and proper translation of these findings may bring forward novel modalities for epithelial rejuvenation and cancer therapeutics.

Pathological evaluation of renal complications in children following allogeneic hematopoietic stem cell transplantation: a retrospective cohort study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients. METHODS: We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years. RESULTS: Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m2) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria. CONCLUSIONS: This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes.

Critical window for the association between early electronic screen exposure and hyperactive behaviors in preschool children.

Electronic screens have become an integral part of modern life, accompanied with growing concerns for children's neuropsychological development. This study aimed to evaluate the associations between measures of early life screen exposure and hyperactive behaviors among preschool children. The study also aimed to investigate their cumulative effects and the critical window for these associations. A cross-sectional survey was conducted among 52 625 mother-child dyads at preschools in LongHua District of Shenzhen, China. A self-administered structured questionnaire was used to assess socio-demographic characteristics, duration of children's electronic screen exposure in each of the first 3 years following birth and the presence of current hyperactive behaviors. A series of logistic regression models were used to examine the relationship between previous screen time and current hyperactive behaviors. A crossover analysis was used to explore the critical window for a significant relationship between screen time and hyperactive behaviors. We found that exposure to electronic screens in the first 3 years of life was associated with hyperactive behaviors in preschool children. A cumulative effect was shown in children with an average daily screen time less than 60 min, with adjusted ORs increasing from 1.262 to 1.989 as screen exposure years increased from 1 to 3 years. A critical window was identified in that children in the first 2 years after birth were vulnerable to electronic screen exposure. Exposure to televisions, mobile phones, and computers were all related to elevated risks for hyperactive behaviors. In conclusion, early screen exposure appears to increase the risk for hyperactive behaviors in preschool children with the presence of a cumulative effect, a critical window and different electronic screens having similar effects.

Joint Effects of Prenatal Folic Acid Supplement with Prenatal Multivitamin and Iron Supplement on Obesity in Preschoolers Born SGA: Sex Specific Difference.

Prenatal maternal nutrient supplementation has been reported to be associated with offspring obesity, but the reports are inconsistent and have mainly ignored the differences between the total children population and children born small for gestational age (SGA). This study aimed to examine the joint effects of folic acid, iron, and multivitamin supplementation during pregnancy on the risk of obesity in preschoolers born SGA. A total of 8918 children aged 3-6.5 years born SGA were recruited from Longhua District in Shenzhen of China in 2021. Their mothers completed a structured questionnaire about the child's and parents' socio-demographic characteristics, maternal prepregnant obesity, and mothers' prenatal supplementation of folic acid, iron, and multivitamin. In addition, the children's current weight and height were measured by trained nurses. Logistic regression models were used to analyze the associations between prenatal supplementations and the current presence of childhood obesity. After controlling for potential confounders, the results of the logistic regression analysis showed that prenatal supplement of folic acid (OR = 0.72, 95% CI = 0.55~0.93) was associated with a lower likelihood of being an obese preschooler born SGA. In contrast, the ingestion of multivitamin or iron supplements during pregnancy did not seem to be related to the likelihood of childhood obesity in preschoolers born SGA. Moreover, cross-over analysis of prenatal folic acid and multivitamin obtained significant negative associations of prenatal folic acid supplement only (OR = 0.73, 95% CI = 0.55~0.97) and combination supplement of folic acid and multivitamin (OR = 0.67, 95% CI = 0.50~0.90) with obesity of preschoolers born SGA; while the cross-over analysis of prenatal folic acid and iron observed significant negative associations between obesity of preschoolers born SGA and a combination supplement of folic acid and iron (OR = 0.70, 95% CI = 0.52~0.96). Furthermore, the aforementioned significant associations were only found in girls and not in boys when the analyses were stratified by sex. Our findings suggest that the prenatal folic acid supplementation may decrease the risk of obesity in preschool girls born SGA, and that this effect may be modified by prenatal multivitamin or iron supplementation.

Parent-child interactions in early life mediating association between prenatal maternal stress and autistic-like behaviors among preschoolers.

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

Associations Between Adolescent Problematic Internet Use and Relationship Problems in Chinese Families: Findings from a Large-scale Survey.

BACKGROUND: Problematic internet use (PIU) is prevalent among Chinese adolescents. There is a need to better understand how the quality of parent-adolescent relationship is associated with adolescent PIU to guide the development of effective prevention and early intervention programs. OBJECTIVE: This study aims to evaluate parent-adolescent conflict and parenting styles as potential risk factors associated with adolescent PIU. METHODS: A sample of 6552 students (aged 10-19 years) from 22 schools in Guangdong, China, was recruited. The participants completed self-report questionnaires measuring their perceptions of conflict with their parents (involving verbal conflict, emotional abuse, and physical abuse) as well as their perceptions of their parents' parenting styles (including parental care and parental control as measured by the Parental Bonding Inventory), and PIU using the Adolescent Pathological Internet Use Scale. Grade level and gender were examined as moderators of these associations. RESULTS: Using multiple regression analyses, we found that greater mother-adolescent conflict, father-adolescent conflict, and parental control, and lower levels of parental care, were associated with higher levels of adolescent PIU (P<.001). The association between mother-adolescent conflict and PIU was stronger in older students than in younger students (P=.04), whereas the association between father-adolescent conflict and PIU was stronger in male students than in female students (P=.02). Compared with those who reported no mother-adolescent conflict, participants who experienced verbal conflict and emotional abuse, but not physical abuse from their mothers, reported higher levels of PIU (P<.001). Compared with those who reported no father-adolescent conflict, participants who experienced verbal conflict, emotional abuse, and physical abuse from their fathers had significantly higher levels of PIU (P<.001, P<.001, and P=.02, respectively). CONCLUSIONS: These findings point to the value of interventions to reduce parental verbal conflict, emotional abuse, and physical abuse, and to increase positive parenting styles, to lower the risk of PIU in Chinese adolescents.

Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone- analyses based on the Huizhou mother-infant cohort.

Objectives: This study aimed to explore the relationship of maternal thyroid function and thyroid resistance parameters with neonatal thyroid-stimulating hormone (TSH). Methods: This work was a longitudinal study. Singleton pregnant women without a history of thyroid disorders were recruited in their first prenatal visit from October 2018 to June 2020. Maternal thyroid markers including TSH, free triiodothyronine (FT3), free thyroxine (FT4), and neonatal TSH were tested in the clinical laboratory of the hospital by electrochemiluminescence immunoassay. Thyroid resistance indices including Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI) were estimated in accordance with maternal FT4 and TSH levels. Multivariable linear and logistic regression was applied to explore the associations of maternal thyroid indices with infantile TSH level. Results: A total of 3,210 mothers and 2,991 newborns with valid TSH data were included for analysis. Multivariable linear regression indicated that maternal thyroid variables were significantly and positively associated with neonatal TSH levels with standardized coefficients of 0.085 for TSH, 0.102 for FT3, 0.100 for FT4, 0.076 for TSHI, 0.087 for TFQI, and 0.089 for TT4RI (all P < 0.001). Compared with the lowest quartile, the highest quartile of TSHI [odds ratio (OR) = 1.590, 95% CI: 0.928-2.724; Ptrend = 0.025], TFQI (OR = 1.746, 95% CI: 1.005-3.034; Ptrend = 0.016), and TT4RI (OR = 1.730, 95% CI: 1.021-2.934; Ptrend = 0.030) were significantly associated with an increased risk of elevated neonatal TSH (>5 mIU/L) in a dose-response manner. Conclusion: The longitudinal data demonstrated that maternal thyroid resistance indices and thyroid hormones in the first half of gestation were positively associated with neonatal TSH levels. The findings offered an additionally practical recommendation to improve the current screening algorithms for congenital hypothyroidism.

First Trimester of Pregnancy as the Sensitive Period for the Association between Prenatal Mosquito Coil Smoke Exposure and Preterm Birth.

Mosquito coils are efficient mosquito repellents and mosquito coil smoke (MCS) contributes to indoor air pollution. However, no prior population-based study has investigated whether prenatal MCS exposure is a risk factor for preterm birth (PTB) and whether exposure to MCS in different trimesters of pregnancy is associated with different levels of risk. The sample involved 66,503 mother-child dyads. Logistic regression models were used to examine the relationships between prenatal MCS exposure during different trimesters of pregnancy and PTB. We found that prenatal MCS exposure was associated with a greater likelihood of PTB (OR = 1.12, 95%CI: 1.05-1.20). The prenatal MCS exposure during the first trimester was associated with 1.17 (95%CI: 1.09-1.25) times the odds of being PTB, which was higher than exposure during the second trimester (OR = 1.11, 95%CI: 1.03-1.19) and during the third trimester (OR = 1.08, 95%CI: 1.01-1.16). In the stratified analysis, prenatal MCS exposure significantly increased PTB risk among girls but not among boys. Our results indicated that maternal MCS exposure during pregnancy was associated with PTB and that the first trimester might be the sensitive period. In light of these findings, public health interventions are needed to reduce prenatal exposure to MCS, particularly during the first trimester of pregnancy.

A clinical model and nomogram for early prediction of gestational diabetes based on common maternal demographics and routine clinical parameters.

AIM: We aimed to develop a risk prediction model for gestational diabetes mellitus (GDM) based on the common maternal demographics and routine clinical variables in Chinese population. METHODS: Individual information was collected from December 2018 to October 2019 by a pretested questionnaire on demographics, medical and family history, and lifestyle factors. Multivariable logistic regression was performed to establish a predictive model for GDM by variables in pre- and early pregnancy. The consistency and discriminative validity of the model were evaluated by Hosmer-Lemeshow goodness-of-fit testing and ROC curve analysis. Internal validation was appraised by fivefold cross-validation. Clinical utility was assessed by decision curve analysis. RESULTS: Total 3263 pregnant women were included with 17.2% prevalence of GDM. The model equation was: LogitP = -11.432 + 0.065 × maternal age (years) + 0.061 × pre-pregnancy BMI (kg/m2 ) + 0.055 × weight gain in early pregnancy (kg) + 0.872 × history of GDM + 0.336 × first-degree family history of diabetes +0.213 × sex hormone usages during pre- or early pregnancy + 1.089 × fasting glucose (mmol/L) + 0.409 × triglycerides (mmol/L) + 0.082 × white blood cell count (109/L) + 0.669 × positive urinary glucose. Homer-Lemeshow goodness-of-fit testing indicated a good consistency between predictive and actual data (p = 0.586). The area under the ROC curve (AUC) was 0.720 (95% CI: 0.697 ~ 0.744). Cross-validation suggested a good internal validity of the model. A nomogram has been made to establish an easy to use scoring system for clinical practice. CONCLUSIONS: The predictive model of GDM exhibited well acceptable predictive ability, discriminative performance, and clinical utilities. The project was registered in clinicaltrial.gov.com with identifier of NCT03922087.

Critical window for the association between prenatal environmental tobacco smoke exposure and preterm birth.

Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25-1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04-1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08-1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24-1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78-2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB.

Maternal exposure to cooking oil fumes during pregnancy and autistic-like behaviors in Chinese preschoolers.

There is growing evidence that cooking oil fumes (COFs) are harmful indoor air pollutants. However, there is a dearth of research investigating whether maternal COFs exposure during pregnancy may affect children's autistic-like behaviors in China. This study aimed to explore this association, and examine the effects of different cooking fuels and ventilation methods used by mothers on the presence of autistic-like behaviors. This study analyzed the survey data of the Longhua Child Cohort Study in 2017 with a total of 62,372 mothers enrolled in this study. A self-administrative questionnaire was used to collect information on socio-demographic characteristics, cooking habits during pregnancy, and autistic-like behaviors (measured using the Autism Behavior Checklist). After adjusting for potential confounders, the results showed that compared with children whose mothers never cooked during pregnancy, children whose mothers cooked sometimes, often, always during pregnancy had the higher risk of autistic-like behaviors. As the amounts of COFs exposed to and the frequency of cooking during pregnancy increased, the risk of a child's autistic-like behaviors also increased. Mothers using natural gas as cooking fuels had a lower risk of their child having autistic-like behaviors, compared with mothers using coal or other cooking fuels. Furthermore, pregnant women using ventilation measures during cooking significantly decreased likelihood of the presence of autistic-like behaviors in their children. These results suggest that maternal exposure to COFs during pregnancy may increase the likelihood of the presence of autistic-like behaviors in offspring. These findings support a recommendation that pregnant women should avoid exposure to COFs and use clean fuels and ventilation equipment in kitchens to reduce the risk of autistic-like behaviors in children.

Network meta-analysis of the optimal time of applying enteral immunonutrition in esophageal cancer patients receiving esophagectomy.

BACKGROUND: Enteral immunonutrition (EIN) has been extensively applied in cancer patients; however, its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN. METHODS: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Meta-analysis with head-to-head approach and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 software. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes. RESULTS: Total 14 studies involving 1071 patients were included. Meta-analysis with head-to-head approach indicated no difference between EIN regardless of the application time and standard EN (SEN); however, subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR = 0.47; 95%CI = 0.26 to 0.84; p = 0.01) and pneumonia (OR = 0.47; 95%CI = 0.25 to 0.90; p = 0.02) and shortened the length of hospitalization (LOH) (MD = - 1.01; 95%CI = - 1.44 to - 0.57; p < 0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes. CONCLUSIONS: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/KJ9UY.

Effect of prenatal nutritional intervention on foetal growth restriction: a real-world study in Shenzhen, China.

OBJECTIVE: Fetal growth restriction (FGR) is the primary cause of infant morbidity and mortality. Although nutritional intervention is generally used to cure FGR, its effects on early- and late-onset FGR have not been reported. This study aimed to resolve this issue in a real-world setting. STUDY DESIGN: We collected the data of pregnant women whose fetuses were diagnosed with FGR and subsequently born at Nanshan Women and Children's Care Hospital in Shenzhen, China. We conducted a MANOVA and series of Cox regression analyses to evaluate the effects of a prenatal nutritional intervention on early and late FGR after adjusting for potential confounders. RESULTS: Our results demonstrated that the average birth weights in the four sub-intervention groups were 50.36-160.05 g higher than those in the nonintervention group. These differences were insignificant with respect to early-onset FGR. In late-onset FGR, however, the interventions led to birth weight increases of 164.95-244.45 g greater than those in the nonintervention group, and these differences were significant. During early-onset FGR, four different nutritional interventions reduced the incidence of small-for-gestational age by 8.00-13.76% relative to the incidence in the nonintervention group, while in late-onset FGR, the incidence decreased by 11.37-17.39%. CONCLUSIONS: Our results based on a real-world setting reaffirmed that a prenatal nutritional intervention could improve the birth outcomes in cases of FGR and further suggested a better effectiveness on late-onset FGR.

Abnormal placental DNA methylation variation in spontaneous preterm birth.

OBJECTIVE: Preterm birth (PTB) has become a major public health concern as the leading cause of neonatal death, but little is understood about its etiology. Children born preterm are also at increased risk of long-term consequences such as neurodevelopmental disorders, adulthood hypertension and diabetes. Recent studies have indicated that DNA methylation may be involved in the occurrence of PTB as well as related adverse outcomes. The latest Infinium EPIC BeadChip extends the coverage of the genome and provides a better tool to help investigate the involvement of DNA methylation in these conditions. METHODS: We conducted this case-control study in three Women and Children's hospitals in South China, and enrolled 32 spontaneous preterm births and 16 term births. We assessed placental DNA methylation profiling of these participants with the Infinium EPIC BeadChip. We identified PTB and gestational age (GA)-associated CpG sites with limma regression model, and applied seqlm to identify PTB-associated regions. We performed gene ontology analysis to further interpret functional enrichment of the identified differentially methylated genes in PTB. RESULTS: We identified a total of 8 differentially methylated positions (DMPs) that were significantly associated with PTB (FDR < 0.1) and a total of 15 DMPs that were associated with GA (FDR < 0.1). In the regional analysis, one differentially methylated region in the SLC23A1 gene overlapped with PTB-associated CpG site. The differentially methylated CpG sites in PTB were mapped to the genes involving in biological processes mainly regarding neurodevelopment, regulation of inflammation and metabolism. CONCLUSION: Our findings suggested that preterm placenta have distinct DNA methylation alterations, and these alteration patterns established at birth provide insight into the long-term consequences of preterm birth.

Placental weight mediates association between prenatal exposure to cooking oil fumes and preterm birth.

Background: There are some reports on association between maternal prenatal cooking oil fume (COF) exposure and preterm birth (PTB), but its mechanism remains poorly understood. Therefore, this study aims to assess whether placental weight mediates their associations.Method: We enrolled 619 pregnant women delivering PTB newborns as cases and 1701 delivering full-term appropriate for gestational age newborns as controls. They were inquired with a self-reported questionnaire about prenatal COF exposure, socio-demographics and obstetric characteristics at Women and Children's Hospitals of Shenzhen and Foshan. After controlling for the potential confounders, a series of logistic and linear regressions were conducted to assess associations among COF exposure, placental weight and PTB, and the mediation of placental weight in the association between COF exposure and PTB.Results: Maternal prenatal COF exposure was significantly associated with PTB and the frequency of prenatal COF exposure was negatively associated with placental weight. Compared with mother who never cooked, those cooking occasionally, sometimes or often increased the risk of PTB, and similarly, those cooking between half to an hour was also showed a higher risk of PTB. Typical Chinese cooking methods including stir-frying, pan-frying and deep-frying were also associated with PTB. Different oil types mainly used, including peanut oil, corn oil and animal oil were associated with PTB as well. Mediation analysis illustrated that placental weight partially mediated 13.60% (95% CI = 10.62-33.20%) of the effects on the association between the frequency of maternal prenatal COF exposure and PTB.Conclusion: Maternal cooking during pregnancy and the frequency of prenatal COF exposure might increase the risk of PTB, in which placenta might play mediation role.

Bidirectional associations between parenting styles and conduct problems in Chinese preschool children: the Shenzhen Longhua Child Cohort Study.

The bidirectional associations between parenting styles and conduct problems in Chinese children attending preschools were rarely discussed. A study covering 171 preschools in Longhua District of Shenzhen, China was conducted among children when they first attended preschools. Parents of children reported the self-perceived parenting styles and their children's conduct problems using validated questionnaires. The bidirectional associations between parenting styles and conduct problems in children were assessed using multivariate linear or logistic regressions in both cross-sectional and cohort settings. In cross-sectional settings, the bidirectional associations were present in all dimensions of parenting styles with children's conduct problems. After 1.01 years of follow-up, increases in parenting dimensions of rejection, control attempts, and favoring subject were significantly associated with children's conduct problems at follow-up, while increases in emotional warmth of parents significantly reduced such risk. In addition, parents of children who had conduct problems at baseline but regressed to normal at follow-up showed decreased scores in negative parenting dimensions. In contrast, among children who developed conduct problems during the study period, the scores of rejection and favoring subject in their parents have increased significantly, while the scores of emotional warmth have decreased. Parent-to-child effect was similar between fathers and mothers, while child-to-parent effect was stronger in fathers than that in mothers. In order to stop the negative feedback loop between poor parenting styles and children's conduct problems, our study underscored the importance of intervention not only in parents but also in their children.

Association between prenatal exposure to indoor air pollution and autistic-like behaviors among preschool children.

Indoor air pollution is a recognized risk factor for a range of negative health outcomes. This study aimed to investigate the association between maternal prenatal exposure to indoor air pollution and the presence of autistic-like behaviors among preschool children. Data were obtained from the Longhua Child Cohort Study in 2017, in which we enrolled a total of 65 317 preschool children. Associations between maternal exposure to four sources of indoor air pollution (e.g., cooking, environmental tobacco smoke (ETS), mosquito coils, and home decoration) during pregnancy and preschool children's autistic traits were analyzed using multivariate logistic regression. Our results showed that maternal exposure to indoor air pollution from four different sources during pregnancy was associated with the presence of children's autistic-like behaviors. There was dose-response relationship between the accumulative exposure to the four different indoor air pollution sources and the risk of autistic-like behaviors. Furthermore, we found a significant additive interaction between prenatal exposure to both cooking and mosquito coil incense on the risk of autistic-like behaviors. Maternal prenatal exposure to the indoor air pollution from four sources might increase with the risk of autistic-like behaviors being present among preschool children, with an additive interaction effect between some pollution sources.

Comparative Efficacy and Safety of Anterograde vs. Retrograde Iodine Staining During Esophageal Chromoendoscopy: A Single-Center, Prospective, Parallel-Group, Randomized, Controlled, Single-Blind Trial.

Background and Aim: Chromoendoscopy with iodine staining is an important diagnostic method for esophageal carcinomas or precancerous lesions. Unfortunately, iodine staining can be associated with numerous adverse events (AEs). We found that the starting position of spraying iodine solution is likely the main reason of causing AEs. We conducted this work to determine whether clinical outcomes from anterograde iodine staining were superior to those achieved after retrograde iodine staining. Methods: A total of 134 subjects with a health risk appraisal flushing (HRA-F) score of >6 for esophageal cancer were randomly assigned to receive anterograde or retrograde iodine staining in the esophagus. The primary endpoints were the pain and the amount of iodine solution consumption. The secondary endpoints were iodine-staining effect, detection yield, and response to starch indicator. Results: Nine patients suffered from pain and six patients revealed positive response to starch indicator in retrograde iodine-staining group; however, no patient reported pain (0/67) and all patients revealed a negative response to starch indicator in anterograde iodine-staining group. The amount of iodine solution consumption in anterograde iodine-staining group (4.97 mL) was significantly lower than that (6.23 mL) in retrograde iodine-staining group; however, the iodine-staining effect and detection yield were comparable between the two groups. Conclusions: Anterograde iodine staining during Lugol chromoendoscopy appears to be as effective, but significantly safer than retrograde iodine staining.