Associated factors of undernutrition in children with congenital heart disease: a cross-sectional study.

Objective: To evaluate the prevalence and associated factors of undernutrition among children with congenital heart disease (CHD) who have not undergone surgeries in China. Methods: This cross-sectional study included 734 CHD children along with their parents. The outcome of interest was undernutrition, including underweight, wasting, and stunting, defined as Z-scores (i.e., weight-for-age, weight-for-height, and height-for-age) ≤-2, according to the World Health Organization (WHO) growth standard. Exposures of interest, containing demographics, obstetric factors, maternal dietary factors, parents' life behaviors and habits, birth-related factors, cardiac-related factors, and preoperative factors, were analyzed using a multivariate logistic regression model to test their associations with undernutrition in CHD children. Results: Overall, 36.1%, 29.7%, and 21.3% of cases were underweight, wasted, and stunted, respectively. Multivariate logistic regression indicated that underweight was associated with demographic factors (including parents' occupational status, family income, and maternal body mass index pre-pregnancy), low birth weight (OR = 4.60, 2.76-7.70), pulmonary hypertension (OR = 4.46, 3.09-6.43), and pneumonia (OR = 1.88, 1.28-2.76). Artificially-fed children were 2.34 (1.36-4.01) times more likely to be underweight. Occupied mothers (OR = 0.62, 0.44-0.88) and fathers (OR = 0.49, 0.26-0.92) served as protective factors, while mothers having gestational complications (OR = 1.56, 1.11-2.18) and exposed to noisy environment (OR = 1.64, 1.11-2.42) during this pregnancy, and pulmonary hypertension (OR = 3.21, 2.30-4.49) increased the chance of wasting in offspring. The odds of being stunted were greater in families with >2 children (OR = 1.88, 1.13-3.14), placental abruption during this pregnancy (OR = 25.15, 2.55-247.89), preterm births (OR = 1.84, 1.02-3.31), low birth weight (OR = 3.78, 2.16-6.62), pulmonary hypertension (OR = 2.35, 1.56-3.53) and pneumonia (OR = 1.93, 1.28-2.90). In subgroup analyses, the associations differed between patients with different feeding patterns (breastfeeding vs. non-breastfeeding), CHD classifications (cyanotic vs. acyanotic), and prematurity (preterm vs. non-preterm). Conclusion: Undernutrition is common in preoperative CHD children. Familial demographics, maternal factors (including having gestational complications and exposure to noisy environment during pregnancy), and patient-related factors (encompassing preterm births, low birth weight, pulmonary hypertension, pneumonia, and feeding pattern) were found to contribute to undernutrition in CHD cases. However, associated factors among the three subgroups of distinct feeding patterns, CHD categorization, and prematurity exhibited varied outcomes, suggesting the necessity for targeted interventions.

The value of Lp(a) and TG/HDLC in peripheral blood to assess the stability of carotid plaque in patients with ischemic stroke.

OBJECTIVE: The objective of this study was to investigate the relationship between lipoprotein (a) (Lp(a)), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), and the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke. METHODS: A total of 142 patients with acute ischemic stroke were selected and divided into group A (59 cases of stable plaque formation) and group B (83 cases of unstable plaque formation) according to the characteristics of carotid artery plaque formation detected by carotid color Doppler ultrasound. The serum Lp(a), lipid metabolism indexes, peripheral blood routine indexes, and related serum inflammatory factors indexes were compared between the two groups. Receiver operating characteristic curve and multivariate logistic regression model were used to analyze the relationship between each index and the formation of carotid unstable plaque. RESULTS: There were no significant differences in serum total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C) between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). There were no significant differences in serum TC, HDL-C, and LDL-C between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). The values of HBA1C, Lp-PLA2, CRP, CysC, Hcy, TNF-α, neutrophils, and NLR in group B were higher than those in group A, and the differences were statistically significant (p < .05). There was no significant difference in FPG, systolic blood pressure, diastolic blood pressure, Hb, white blood cells, platelets, and lymphocytes between groups A and B (p > .05). The results of logistic regression model showed that the increase of Lp(a), TG/HDL-C, HBA1C, Lp-PLA2, CRP, CysC, Hcy, and NLR could increase the risk of carotid artery unstable plaque in patients with ischemic stroke (p < .05). CONCLUSION: Lp(a) and TG/HDL-C have certain value in evaluating the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke, and the increased levels of LP (a) and TG/HDL-C will significantly increase the risk of carotid unstable plaque in patients.

Maternal anaemia during early pregnancy and the risk of neonatal outcomes: a prospective cohort study in Central China.

BACKGROUND: The purpose of this study was to explore the association between anaemia during early pregnancy and the risk of neonatal outcomes. METHODS: We collected clinical data from pregnant women (≥18 years) who received their first antenatal care between 8 and 14 weeks of gestation in Hunan Provincial Maternal and Child Health Care Hospital. Multiple logistic regression models and restricted cubic spline regression models were used to analyse the association between anaemia during early pregnancy and the risk of neonatal outcomes. In addition, sensitivity analysis was further performed to assess the robustness of the results. RESULTS: The prospective cohort study ultimately included 34 087 singleton pregnancies. In this study, the rate of anaemia during early pregnancy was 16.3%. Our data showed that there was a positive relationship between the rate of preterm birth, low birth weight as well as small for gestational age (SGA) and the severity of maternal anaemia (Ptrend<0.05). After adjustment, the association of early pregnancy anaemia and haemoglobin (Hb) levels with the risk of preterm birth (mild anaemia adjusted OR (aOR) 1.37 (95% CI 1.25 to 1.52), moderate anaemia aOR 1.54 (95% CI 1.35 to 1.76) and severe anaemia aOR 4.03 (95% CI 2.67 to 6.08), respectively), low birth weight (mild anaemia aOR 1.61 (95% CI 1.44 to 1.79), moderate anaemia aOR 2.01 (95% CI 1.75 to 2.30) and severe anaemia aOR 6.11 (95% CI 3.99 to 9.36), respectively) and SGA (mild anaemia aOR 1.37 (95% CI 1.25 to 1.52), moderate anaemia aOR 1.54 (95% CI 1.35 to 1.76) and severe anaemia aOR 2.61 (95% CI 1.74 to 4.50), respectively; Pnon-linear<0.05) was observed. However, no association was found between early pregnancy anaemia or Hb levels and the risk of congenital malformations. Sensitivity analysis verified the stability of the results. CONCLUSIONS: Maternal anaemia during early pregnancy was associated with an increased risk of preterm birth, low birth weight and SGA and their rates may increase with the severity of maternal anaemia. TRIAL REGISTRATION NUMBER: ChiCTR1800016635.

The risk of attention-deficit hyperactivity disorder among children with congenital heart disease: A systematic review and meta-analysis.

BACKGROUND: Although current treatments are effective in dealing with congenital heart disease (CHD), non-cardiac comorbidities such as attention-deficit hyperactivity disorder (ADHD) have received widespread attention. The purpose of this systematic review and meta-analysis is to assess the risk of ADHD associated with CHD. METHODS: The literature search was carried out systematically through eight different databases by the end of September 2022. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. The heterogeneity of the studies was assessed by the Cochran Q test and the I2 statistic. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity. RESULTS: Eleven studies were included in this study, which involved a total of 296 741 participants. Our study showed that the children with CHD were at a significantly increased risk of ADHD compared with the reference group (OR = 2.98, 95% CI: 2.18-4.08). The results were moderately heterogeneous. These factors including study design, geographic region and study quality were identified as the first three of the most relevant heterogeneity moderators by subgroup analyses. Sensitivity analysis yielded consistent results. There was no evidence of publication bias. CONCLUSIONS: The present study suggests that CHD children have a significantly higher risk of ADHD when compared with those without CHD. Early identification and intervention of ADHD is important to reduce its symptoms and adverse effects; therefore, clinicians should increase screening for ADHD in children with CHD and intervene promptly to reduce its effects whenever possible.

Correlation Analysis of Macrophage Distribution and Pathological Features of Carotid Atherosclerotic Plaque.

BACKGROUND: Macrophages play an important role in maintaining the chronic inflammatory of atherosclerosis (AS) and are hallmark of atherosclerotic plaques. They differentiate into different subpopulations under the influence of oxidized lipids and cytokines and play different roles in the formation and development of plaque. To explore the differences in the amount and distribution of different macrophage subpopulations around different carotid plaque pathological features in human AS, and based on these results, to explore the correlation between some macrophage subpopulations and AS pathological features. METHODS: First, we analyzed the single cells RNA-sequence data from the Gene Expression Omnibus DataSets (GSE159677). Second, we investigated the distribution difference of macrophage subpopulations in 61 surgically resected AS plaques by markers staining include CD68, inducible nitric oxide synthase, Arg-1, CD163 and HO-1. RESULTS: The result of single cells RNA-Sequence analysis showed that there were a large number of macrophages infiltrated in AS and they can be categorized into different subpopulations with different transcriptional features and functions; moreover in different part of AS (calcified AS core versus proximal adjacent), the total number and subpopulation ratios were all different. The result of staining analysis showed that macrophages mainly distributed in some pathological lesions such as necrosis, fibrous tissue degeneration, cholesterol crystallization etc., and different subpopulations were distributed differently in these lesions. CONCLUSIONS: This study confirmed that macrophages were heavily infiltrated in atherosclerotic plaques, and there existed subtype variability in different pathological lesions; meanwhile, these results suggested that different macrophage subpopulations may contribute differently in different pathological lesions.

CD30 plays a role in T-dependent immune response and T cell proliferation.

CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily and expressed in both normal and malignant lymphoid cells. However, the role of CD30 in lymphopoiesis is not known. In this study, we showed CD30 was expressed both in T and B cells, but its deficiency in mice had no effect on T- and B-cell development. In fact, CD30 deficiency attenuated B-cell response to T-cell-dependent antigens. The impaired B cell response in CD30-deficient mice is caused by the reduction of activation-induced cytidine deaminase (AID) expression. Moreover, CD30-deficient mice exhibited decreased TCR-mediated T cell proliferation and slightly impaired TCR signaling. High-throughput RNA sequencing analysis revealed that CD30 deficiency led to a decrease of FOXO-autophagy axis in T cells upon TCR stimulation. Thus, CD30 positively regulates T-cell-dependent immune response and T cell proliferation.

The effect of China's many-child policy on the number of births and the prevalence of serious teratogenic and disabling defects in Hunan Province.

BACKGROUND: To research the effect of China's many-child policy on the number of births and the prevalence of serious teratogenic and disabling defects (STDDs) in Hunan province. METHODS: We performed an observational study based on the Birth Defect (BD) Surveillance System of Hunan Province and chose STDD case cards. From 2012-2022, we defined the following 4 periods: the one-child policy (OCP) (2012.01-2013.12), partial two-child policy (PTCP) (2014.1-2015.12), universal two-child policy (UTCP) (2016.1-2020.12), and the early stage of the three-child policy (ETCP) (2021.1-2022.12). Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine the association of policy changes with STDDs. Crame'r's V was calculated to estimate the effect sizes. Joinpoint regression analysis and annual percent change (APC) were used for each segment of the trend. RESULTS: A total of 1,652,079 births were included in this analysis. Joinpoint regression analysis showed that the number of perinatal births increased from 2012 to 2017, with APC = 9.52 (95% CI: 7.2 to 11.8), and decreased from 2017 to 2022, with an APC = -10.04 (95% CI: -11.9 to -8.1). The number of mothers over 30 years old gradually increased, from 25.54% during the OCP period to 54.05% during the ETCP period (Ptrend < 0.001). With policy changes, the total prevalence of STDDs increased from 28.10 per 10,000 births during the period of OCP into 46.77 per 10,000 births during the ETCP period by 66.44%. The live birth prevalence of STDDs increased only during the ETCP period (PTCP: OR = 1.27, 95% CI: 0.99-1.24, p = 0.057, UTCP: OR = 1.22, 95% CI: 0.99-1.52, p = 0.067, ETCP: OR = 1.75, 95% CI: 1.37-2.24, p < 0.001). Over the past ten years, there was a decrease in the gestational age at diagnosis (*F = 772.520, p < 0.001), from 24.49 ± 5.65 weeks in 2012 to 20.77 ± 5.17 weeks in 2022. From 2012 to 2022, the percentage of deaths within 7 days decreased with APC = -18.85 (95% CI: -26.4- -10.5, P > 0.05). CONCLUSION: Many-child policies were associated with a moderate increase in fertility especially for women in urban areas and older women. However, they have lost the ability to control birth since 2017. The total prevalence of STDDs increased over the entire period, but the live birth prevalence increased only during the ETCP period. The gestational age at diagnosis decreased and the percentage of deaths within 7 days decreased.

A drug-delivery depot for epigenetic modulation and enhanced cancer immunotherapy.

DNA methyltransferase inhibitors (DNMTis) have found widespread application in the management of cancer. Zebularine (Zeb), functioning as a demethylating agent, has exhibited notable advantages and enhanced therapeutic efficacy in the realm of tumour immunotherapy. Nevertheless, due to its lack of targeted functionality, standalone Zeb therapy necessitates the administration of a substantially higher dosage. In this investigation, we have devised an innovative nanodrug formulation, comprising the DNA methyltransferase inhibitor Zeb and pH-responsive chitosan (CS), hereinafter referred to as CS-Zeb nanoparticles (NPs). Our findings have unveiled that CS-Zeb NPs manifest heightened drug release within an acidic milieu (pH 5.5) in comparison to a neutral environment (pH 7.4). Furthermore, in vivo studies have conclusively affirmed that, in contrast to equivalent quantities of Zeb in isolation, the nanocomplex significantly curtailed tumour burden and protracted the survival duration of the B16F10 tumour-bearing murine model. Additionally, CS-Zeb NPs elicited an augmentation of CD8+ T cells within the peripheral circulation of mice and tumour-infiltrating lymphocytes (TILs). Notably, the dosage of CS-Zeb NPs was reduced by a remarkable 70-fold when juxtaposed with Zeb administered in isolation. To summarise, our study underscores the potential of CS-Zeb NPs as an alternative chemotherapeutic agent for cancer treatment.

Fertility intentions to have a second or third child among the childbearing-age population in Central China under China's three-child policy: A cross-sectional study.

Background: On May 31, 2021, the Chinese authorities announced that couples can have up to three children, aiming to stimulate a rise in fertility levels. However, there is limited research on second and third birth intentions of the childbearing-age population under China's three-child policy, and the existing results are inconsistent. Methods: A cross-sectional survey was performed in Central China from June to August 2022. A total of 13 479 respondents aged 20-49 were enrolled in the study through a multi-stage sampling method. Data on the intentions to have a second or third child were collected using anonymized questionnaires. Descriptive statistics were performed to assess fertility intentions. Multivariate logistic regression analyses were used to assess the associations between fertility intentions and the related factors. Results: Among families with a single child, 29.7% (1444 / 4859) of the respondents intended to have a second child, while among two-child families, 10.6% (750 / 7056) respondents intended to have a third child. Overall, participants indicated that the ideal number of children was 1.85 ± 0.52. The age-specific fertility intentions of the one-child families were always higher than those of two-child families; however, based on couples' age groups, the number of ideal children reported by two-child families was always higher than that of one-child families. Fertility intentions were influenced by the respondents' gender, age, residence, marital status, educational level, average working time, childcare support, marital satisfaction, accessibility of educational resources, health condition of both spouses, loan situation, size of living house and the gender of the first child or second child. Conclusions: The general prevalence of the second and third birth intention of the childbearing-age population in Central China is not high. To increase the birth rate, it is necessary to create a favourable fertility context and offer supportive measures.

Association of MTR gene polymorphisms with the occurrence of non-syndromic congenital heart disease: a case-control study.

To exhaustively explore the association of infant genetic polymorphisms of methionine synthase (MTR) gene with the risk of non-syndromic congenital heart disease (CHD). A hospital-based case-control study involving 620 CHD cases and 620 health controls was conducted from November 2017 to March 2020. Eighteen SNPs were detected and analyzed. Our date suggested that the genetic polymorphisms of MTR gene at rs1805087 (GG vs. AA: aOR = 6.85, 95% CI 2.94-15.96; the dominant model: aOR = 1.77, 95% CI 1.35-2.32; the recessive model: aOR = 6.26, 95% CI 2.69-14.54; the addictive model: aOR = 1.81, 95% CI 1.44-2.29) and rs2275565 (GT vs. GG: aOR = 1.52, 95% CI 1.15-1.20; TT vs. GG: aOR = 4.93, 95% CI 1.93-12.58; the dominant model: aOR = 1.66, 95% CI 1.27-2.17; the recessive model: aOR = 4.41, 95% CI 1.73-11.22; the addictive model: aOR = 1.68, 95% CI 1.32-2.13) were significantly associated with the higher risk of CHD. And three haplotypes of G-A-T (involving rs4659724, rs95516 and rs4077829; OR = 5.48, 95% CI 2.58-11.66), G-C-A-T-T-G (involving rs2275565, rs1266164, rs2229276, rs4659743, rs3820571 and rs1050993; OR = 0.78, 95% CI 0.63-0.97) and T-C-A-T-T-G (involving rs2275565, rs1266164, rs2229276, rs4659743, rs3820571 and rs1050993; OR = 1.60, 95% CI 1.26-2.04) were observed to be significantly associated with risk of CHD. Our study found that genetic polymorphisms of MTR gene at rs1805087 and rs2275565 were significantly associated with higher risk of CHD. Additionally, our study revealed a significant association of three haplotypes with risk of CHD. However, the limitations in this study should be carefully taken into account. In the future, more specific studies in different ethnic populations are required to refine and confirm our findings.Trial registration: Registration number: ChiCTR1800016635; Date of first registration: 14/06/2018.

Efficacy of neurointerventional therapy in patients with ischemic stroke and risk factors affecting cognitive function recovery.

OBJECTIVE: To investigate the efficacy of neurointervention combined with intravenous thrombolysis in ischemic stroke patients and the risk factors affecting cognitive function recovery. METHODS: A total of 114 patients with acute ischemic stroke (AIS) treated in Baoji People's Hospital from January 2017 to December 2020 were retrospectively selected and divided into an observation group and a control group according to different treatment methods. The observation group was treated with neurointervention + intravenous thrombolysis (n = 64), and the control group underwent intravenous thrombolysis (n = 50). The efficacy, recanalization rate, incidence of adverse events, National Institutes of Health Stroke Scale (NIHSS) score, Mini-Mental State Examination (MMSE) score and modified Rankin Scale (mRS) score were evaluated and compared between the two groups. Patients were further divided into a cognitive dysfunction group and a non-disorder group according the MMSE score after treatment, and logistics regression was used to analyze the risk factors of cognitive dysfunction. RESULTS: The overall response rate and the total recanalization rate of the observation group were significantly higher than those of the control group (both P < 0.05). Compared with those before operation, the NIHSS score at 7 d after operation and the mRS score 3 months after operation decreased, while the MMSE score increased in both groups (P < 0.05). The postoperative NIHSS score and mRS score were lower and MMSE score was higher in the observation group than those in the control group (P < 0.05). No significant difference was identified in the incidence of adverse events between the two groups (P > 0.05). Logistics regression analysis revealed that age, diabetes mellitus, hyperlipidemia and lesions at critical sites were independent risk factors for cognitive impairment in patients with AIS. CONCLUSION: Interventional thrombectomy combined with intravenous thrombolysis is effective in the treatment of cerebral infarction. This regimen can reduce neurological deficits and improve the recanalization rate. In addition, age, diabetes, hyperlipidemia and lesions at critical sites are independent risk factors for the development of cognitive impairment in AIS patients.

Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study.

Objective: The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. Methods: We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. Results: At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10-4, P FDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected. Conclusions: The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa's role in the pathophysiology of T1D.

Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study.

BACKGROUND: Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal MTRR gene with CHD risk in offspring. METHODS: A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. RESULTS: The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. CONCLUSIONS: Maternal MTRR gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.

Effect of the interaction between advanced maternal age and pre-pregnancy BMI on pre-eclampsia and GDM in Central China.

INTRODUCTION: To investigate the independent and combined effects of advanced maternal age and pre-pregnancy body mass index (BMI) on the risk of pre-eclampsia and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Logistic regression models were used to estimate the OR and 95% CIs of pre-eclampsia and GDM with advanced maternal age and pre-pregnancy BMI, respectively, and the interaction between advanced maternal age and pre-pregnancy BMI. We also used causal mediation analysis to assess the mediating role of pre-pregnancy BMI on maternal age-pre-eclampsia/GDM associations. RESULTS: In this study, 788 cases (2.31%) were diagnosed with pre-eclampsia and 5430 cases (15.92%) were diagnosed with GDM. We found that advanced maternal age was associated with a higher risk for pre-eclampsia and GDM, with adjusted ORs (aORs) of 1.74 (95% CI 1.49-2.05) and 1.76 (95% CI 1.65-1.89) after adjusting for potential confounders, respectively. In addition, maternal pre-pregnancy overweight/obesity was associated with the risk of pre-eclampsia and GDM, with the corresponding aORs of 3.64 (95% CI 3.12-4.24) and 1.71 (95% CI 1.60-1.85), respectively. We also observed the interaction between maternal age and pre-pregnancy BMI for the risk of pre-eclampsia/GDM (all p for interaction <0.001). In the mediating effect analysis, we found that maternal pre-pregnancy BMI mediated the associations between maternal age and the development of pre-eclampsia and GDM. CONCLUSIONS: Advanced maternal age and pre-pregnancy BMI were respectively associated with the risk of pre-eclampsia/GDM, and there was an interaction between the two risk factors. In addition, we found that pre-pregnancy BMI served as a mediator of the association between advanced maternal age and the risk of pre-eclampsia/GDM, providing an essential target for the prevention of maternal overweight/obesity.

Cloned antibodies from patients with HIT provide new clues to HIT pathogenesis.

Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction characterized by antibodies that recognize platelet factor 4/heparin complexes (PF4/H) and activate platelets to create a prothrombotic state. Although a high percentage of heparin-treated patients produce antibodies to PF4/H, only a subset also makes antibodies that are platelet activating (PA). A close correlation between PA antibodies and the likelihood of experiencing HIT has been demonstrated in clinical studies, but how PA (presumptively pathogenic) and nonactivating (NA) (presumptively benign) antibodies differ from each other at the molecular level is unknown. To address this issue, we cloned 7 PA and 47 NA PF4/H-binding antibodies from 6 patients with HIT and characterized their structural and functional properties. Findings showed that PA clones differed significantly from NA clones in possessing 1 of 2 heavy chain complementarity-determining region 3 (HCDR3) motifs, RX1-2R/KX1-2R/H (RKH) and YYYYY (Y5), in an unusually long complementarity-determining region 3 (≥20 residues). Mutagenic studies showed that modification of either motif in PA clones reduced or abolished their PA activity and that appropriate amino acid substitutions in HCDR3 of NA clones can cause them to become PA. Repertoire sequencing showed that the frequency of peripheral blood IgG+ B cells possessing RKH or Y5 was significantly higher in patients with HIT than in patients without HIT given heparin, indicating expansion of B cells possessing RKH or Y5 in HIT. These findings imply that antibodies possessing RKH or Y5 are relevant to HIT pathogenesis and suggest new approaches to diagnosis and treatment of this condition.

Association of Maternal Betaine-Homocysteine Methyltransferase (BHMT) and BHMT2 Genes Polymorphisms with Congenital Heart Disease in Offspring.

To systematically explore the association of single nucleotide polymorphisms (SNPs) of maternal BHMT and BHMT2 genes with the risk of congenital heart disease (CHD) and its three subtypes including atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) in offspring. A hospital-based case-control study involving 683 mothers of CHD children and 740 controls was performed. Necessary exposure information was captured through epidemiological investigation. Totally twelve SNPs of maternal BHMT and BHMT2 genes were detected and analyzed systematically. The study showed that maternal BHMT gene polymorphisms at rs1316753 (CG vs. CC: OR = 1.96 [95% CI 1.41-2.71]; GG vs. CC: OR = 1.99 [95% CI 1.32-3.00]; dominant model: OR = 1.97 [95% CI 1.44-2.68]) and rs1915706 (TC vs. TT: OR = 1.93 [95% CI 1.44-2.59]; CC vs. TT: OR = 2.55 [95% CI 1.38-4.72]; additive model: OR = 1.77 [95% CI 1.40-2.24]) were significantly associated with increased risk of total CHD in offspring. And two haplotypes were observed to be significantly associated with risk of total CHD, including C-C haplotype involving rs1915706 and rs3829809 in BHMT gene (OR = 1.30 [95% CI 1.07-1.58]) and C-A-A-C haplotype involving rs642431, rs592052, rs626105, and rs682985 in BHMT2 gene (OR = 0.71 [95% CI 0.58-0.88]). Besides, a three-locus model involving rs1316753 (BHMT), rs1915706 (BHMT), and rs642431 (BHMT2) was identified through gene-gene interaction analyses (P < 0.01). As for three subtypes including ASD, VSD, and PDA, significant SNPs and haplotypes were also identified. The results indicated that maternal BHMT gene polymorphisms at rs1316753 and rs1915706 are significantly associated with increased risk of total CHD and its three subtypes in offspring. Besides, significant interactions between different SNPs do exist on risk of CHD. Nevertheless, studies with larger sample size in different ethnic populations and involving more SNPs in more genes are expected to further define the genetic contribution underlying CHD and its subtypes.

Generation and Characterization of Recombinant Pseudorabies Virus Delivering African Swine Fever Virus CD2v and p54.

African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies recombinant virus (PRV) expressing ASFV CD2v and p54 proteins (PRV-∆TK-(CD2v)-∆gE-(p54)) using CRISPR/Cas9 and homologous recombination technology. PRV-∆TK-(CD2v)-∆gE-(p54) effectively delivers CD2v and p54, and it exhibits reduced virulence. Immunization with PRV-∆TK-(CD2v)-∆gE-(p54) neither induces pruritus nor causes systemic infection and inflammation. Furthermore, a double knockout of the TK and gE genes eliminates the depletion of T, B, and monocytes/macrophages in the blood caused by wild-type viral infection, decreases the proliferation of granulocytes to eliminate T-cell immunosuppression from granulocytes, and enhances the ability of the immune system against PRV infection. An overexpression of CD2v and p54 proteins does not alter the characteristics of PRV-∆TK/∆gE. Moreover, PRV-∆TK-(CD2v)-∆gE-(p54) successfully induces antibody production via intramuscular (IM) vaccination and confers effective protection for vaccinated mice upon challenge. Thus, PRV-∆TK-(CD2v)-∆gE-(p54) demonstrates good immunogenicity and safety, providing highly effective protection against PRV and ASFV. It potentially represents a suitable candidate for the development of a bivalent vaccine against both PRV and ASFV infections.

Parental pre-pregnancy body mass index and risk of low birth weight in offspring: A prospective cohort study in central China.

Background: Low birth weight (LBW) is one of the most common adverse pregnancy outcomes. Previous studies have consistently shown that maternal body mass index (BMI) status before and during pregnancy is associated with LBW. However, previous studies lacked an association between paternal BMI and the conjunction effect of a couple's BMI and LBW in the offspring. Therefore, we established a cohort of pre-pregnancy couples to prospectively assess the relationship between maternal and paternal pre-pregnancy BMI and offspring LBW, very low birth weight (VLBW), and extremely low birth weight (ELBW). Methods: A prospective cohort study was established in Central China. A total of 34,104 pregnant women with singleton pregnancies at 8-14 gestational weeks and their husbands were finally enrolled and followed to 3 months postpartum. The multivariate logistic regression and restrictive cubic spline model were used to explore the relationship between parental pre-pregnancy BMI and the risk of LBW, VLBW, and ELBW in offspring. Results: Of the 34,104 participants, maternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.720, 95% CI = 1.533 ~ 1.930; obesity: OR = 1.710, 95% CI = 1.360 ~ 2.151), VLBW (overweight: OR = 2.283, 95% CI = 1.839 ~ 2.834; obesity: OR = 4.023, 95% CI = 2.855 ~ 5.670), and ELBW (overweight: OR = 3.292, 95% CI = 2.151 ~ 5.036; obesity: OR = 3.467, 95% CI = 1.481 ~ 8.115), while underweight was associated with a higher risk of LBW (OR = 1.438, 95% CI = 1.294 ~ 1.599) and a lower risk of ELBW (OR = 0.473, 95% CI = 0.236 ~ 0.946). Paternal pre-pregnancy overweight and obesity were associated with a higher risk of LBW (overweight: OR = 1.637, 95% CI = 1.501 ~ 1.784; obesity: OR = 1.454, 95% CI = 1.289 ~ 1.641) and VLBW (overweight: OR = 1.310, 95% CI = 1.097 ~ 1.564; obesity: OR = 1.320, 95% CI = 1.037 ~ 1.681), while underweight was associated with a lower risk of LBW (OR = 0.660, 95% CI = 0.519 ~ 0.839). Parents who were both excessive-weights in pre-pregnancy BMI, as well as overweight mothers and normal-weight fathers before pre-pregnancy, were more likely to have offspring with LBW, VLBW, and ELBW. Dose-response relationship existed between parental pre-pregnancy and LBW, VLBW, and ELBW, except for paternal BMI and ELBW. Conclusions: Parental pre-pregnancy BMI was associated with the risk of LBW in offspring. Management of weight before pregnancy for couples might help reduce their adverse pregnancy outcomes in future intervention studies.

The Effect Of Small Bone Window Craniotomy Removal on Lactic Acid and CRP in Patients with Hypertensive Intracerebral Hemorrhage in the Basal Ganglia.

Background: Hypertensive intracerebral hemorrhage (HICH) seriously endangers the quality of life of patients and can even lead to death. Craniotomy is a common treatment method for HICH. Objective: The aim of this study was to investigate the efficacy of two different sizes of craniotomy in patients with HICH, as well as to evaluate their effects on C-reactive protein (CRP) and blood lactate levels. Materials and Methods: A total of 72 patients with HICH in the basal ganglia were operated on in our hospital from February 2017 to March 2019 and randomly divided into two groups: the small bone window (SBW) group (n = 37) and the large bone flap group (n = 35). The curative effects of the two kinds of operations were evaluated by the length of operation, the days of hospitalization, the rate of hematoma clearance, the rate of rebleeding, and the incidence of complications. Additionally, the levels of CRP and lactate were compared between the two groups. Results: The results showed that the average intraoperative time, hospital stay, rebleeding rate, and postoperative complications of patients in the SBW group were less than those in the large bone flap group. Moreover, the number of patients in the SBW group with good postoperative recovery, including class V and class IV, was higher than that in the large bone flap group. Minimally invasive craniotomy with SBW reduced the lactic acid and CRP levels more quickly than the large bone flap group. Conclusions: An SBW was superior to a large bone flap in terms of the operative effect and lactate and CRP levels. It is concluded that an SBW has significant advantages over a large bone flap.