Association of congenital heart disease and neurodevelopmental disorders: an observational and Mendelian randomization study.

BACKGROUND: This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs. METHODS: This observational study uses data from the National Survey of Children's Health (2020-2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects. RESULTS: A total of 85,314 children aged 0-17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p < 0.05) had a suggestive association with speech or language disorders. The severity of current heart condition (p = 0.08) has a potential statistically significant association with attention deficit hyperactivity disorder(ADHD). In PSM samples, ADHD(p = 0.003), intellectual disability(p = 0.012), and speech or language disorders(p < 0.001) were all significantly associated with CHD. The severity of current heart condition (p < 0.001) also had a significant association with autism. MR analysis did not find causality between genetically proxied congenital cardiac malformations and the risk of NDDs. CONCLUSIONS: Our study shows that children with CHD have an increased risk of developing NDDs. Heart conditions currently and severity of current heart conditions were also significantly associated with these NDDs. In the future, we need to try more methods to clarify the causal relationship between CHD and NDDs.

Application of "Internet+" cognitive-behavioral intervention in caregivers of children with congenital heart disease undergoing elective surgery during the COVID-19 pandemic.

OBJECTIVE: To explore the effects of cognitive and behavioral interventions for caregivers of children undergoing interventional surgery for congenital heart disease (CHD) during COVID-19. METHODS: A prospective study was conducted on 140 children with CHD who were hospitalized in the Department of Cardiology in a children's hospital from March 2020 to March 2022. The children were randomly divided into an intervention group and a control group, with 70 cases in each group. In the control group, caregivers gave routine care, and in the intervention group, "Internet+" cognitive and behavioral interventions were given. The psychological status of caregivers before and after intervention, day care ability on the operation day, readiness for hospital discharge of the caregivers, sleep quality, and postoperative complications of the children, the medication compliance, review compliance and satisfaction were compared between the two groups. RESULTS: During the COVID-19 pandemic, the anxiety and depression scores of caregivers in the intervention group were significantly lower than those in the control group (P<0.05), and the caregiving ability and readiness for hospital discharge of the caregivers in the intervention group were better than those in the control group (P<0.05). The sleep quality of children in the intervention group was significantly better than that in the control group during the first week after operation (P<0.05). Postoperative complications were significantly fewer in the intervention group than in the control group (χ 2=24.433, P<0.001). The medication compliance, review compliance, and satisfaction were higher in the intervention group than in the control group (P<0.05). CONCLUSION: During the pandemic period of COVID-19, "Internet+" cognitive and behavioral intervention has a good effect and should be promoted in clinical practice.

Differences and determinants for polluted area, urban and rural residents' willingness to hand over and pay for waste mobile phone recycling: Evidence from China.

Currently, China has the largest generation volume of waste mobile phones (WMPs), but the recycling rate is still negligible. How to improve the willingness to hand (WTH) over to formal recycling channels and willingness to pay (WTP) have become the most core problems in the e-waste recycling industry. As the important link between WMPs generation and collection, the residents' role and function are attracting more and more attention. Thus, this study is designed to identify the determinants of the residents' WTH and WTP for WMPs through the contingent valuation method (CVM). At the same time, it will explore the current existing gaps from the urban and rural residents. Especially, this study also considers Guiyu Town as one special rural region for understanding the differences with other regions. The results show that the respondents generally have the relatively lower knowledge and cognition on WMPs recycling. Only 9.4% respondents are satisfied with the current government's management of WMPs. Personal information leakage is an important reason for low WTH. The WTH of Guiyu, urban and rural respondents were 51.3%, 45.9% and 41.2%, respectively; while their WTP were 46.80%, 31.70% and 37.80%, respectively. Finally, it is estimated that their WTP values were 18.75 ($2.81), 16.14 ($2.42) and 15.85 ($2.38) RMB per unit, respectively. The demographic variables, cognition and attitude are important factors on all residents' WTH and WTP. Meanwhile, it is indicated that if owning higher WTH, the residents will trend to higher WTP. Especially, the WTH and WTP of Guiyu residents are higher than other residents.

Evaluation of Carotid Artery Elasticity in Early Stage of Kawasaki Disease by Two-Dimensional Speckle Tracking Imaging: A Pilot Study.

OBJECTIVES: Children with Kawasaki disease (KD) often develop impaired arterial function. The aim of the study was to assess the feasibility and efficacy of two-dimensional speckle tracking technique (2DSTI) for the evaluation of carotid artery elasticity in children with early-stage KD. METHODS: Children with KD (n = 97), age and sex-matched children with fever (n = 18), and healthy controls (n = 24) were included. Children with KD were subsequently divided into a coronary artery lesion group (CAL group, 27 cases) and a noncoronary artery lesion group (nCAL group, 70 cases) based on the results of echocardiography. The carotid circumferential peak strain (CCS) and carotid intima-media thickness (CIMT) for the children in each group were measured, and the laboratory indicators for each group were collected. RESULTS: The CCS of children with KD was lower than that of children with fever and healthy controls (P = .001 and .008), whereas CIMT was not significantly different among the groups. Moreover, the CCS of children in the CAL group was lower than that of children in the nCAL group and healthy controls (P = .001 and .000, respectively), whereas the CIMT of children in the CAL group was higher than that of children in the nCAL group (P = .014). In children with KD, CCS was negatively correlated with C-reactive protein (CRP) and alanine aminotransferase (ALT) (r = -.419, P = .001; and r = -.305, P = .003). However, CCS was negatively correlated with CRP (r = -.508, P = .007) but not ALT (r = -.176, P = .379) in children in the CAL group. CONCLUSION: CCS determined based on 2DSTI can reflect changes in the carotid artery elasticity function in the early stage of KD.

Composition changes, releases, and potential exposure risk of PBDEs from typical E-waste plastics.

Since Stockholm Convention listed polybrominated diphenyl ethers (PBDEs) as persistent organic pollutants and banned their addition, alternative halogen flame retardants (AHFRs) have been substituted for PBDEs. This study systematically investigates the change trends of PBDEs and AHFRs from typical e-waste plastics and dust, as well as clarifying human exposure risks of PBDEs in formal and informal e-waste recycling enterprises, repair store and residential building. The results show that the PBDEs levels in five typical types of e-waste vary in the range of 1.08 × 10-3-30.8 µg/g, meeting the requirements of RoHS regulation. Compared with the residential buildings (1.49-1.68 µg/g), PBDEs in the dust from the formal and informal e-waste recycling enterprises are much higher, ranging from 4.70 to 536 µg/g. BDE-209 is the main congener in most e-waste plastic and dust samples. Meanwhile, AHFRs have become the important composition (3.5-61.5%) in e-waste plastics, while its contribution is lower in dust, implying the higher enrichment efficiency of PBDEs. For PBDEs exposure, the dust intake risk of PBDEs is much higher than skin contact for the workers, and the highest hazard quotient (HQ) value (1.40 × 10-1) and cancer risk (CR) value (1.21 × 10-7) both imply safe exposure levels.

Synthesis of p-O-Alkyl Salicylanilide Derivatives as Novel EGFR Inhibitors.

Preclinical Research Epidermal growth factor receptor (EGFR), a validated target for anticancer drugs, plays a critical role in tumorigenesis and tumor development. A series of p-O-alkyl salicylanilide derivatives were designed and synthesized as novel EGFR inhibitors using a salicylic acid scaffold. A simulated six-membered ring strategy formed through intramolecular hydrogen bonds was employed to mimic the planar quinazoline of the EGFR antagonist, gefitinib. The derived compounds with hydroxyl at the ortho position were more potent than ones with methoxyl group. In particular, compounds 5d and 5b displayed significant EGFR inhibitory (IC50 values = 0.30 and 0.45 µM, respectively) activity as well as potent antiproliferative activity in A431 and HCT-116 tumor cells. These salicylanilides could be considered as promising lead compounds for developing novel EGFR inhibitors.

Relationship of interleukin-6-572C/G promoter polymorphism and serum levels to post-percutaneous coronary intervention restenosis.

BACKGROUND: It has been recently reported that inflammatory mechanisms play an important role in in-stent restenosis (ISR) processes. Inflammatory factors after percutaneous coronary intervention (PCI) for dynamic monitoring can probably predict ISR. Functional polymorphisms in the promoter region of genes coding for inflammatory factors might be important for determining the magnitude of the inflammatory response. Thus, in the present study, we aimed to investigate the serial changes in serum interleukin-6 (IL-6) levels before and after PCI and the relationship between the -572C/G polymorphism in the promoter region of the IL-6 gene and ISR. We also discussed genetic polymorphisms in the inflammatory response to PCI. METHODS: A total of 437 patients who successfully underwent bare metal stent (BMS) implantation with a follow-up angiography were divided into an ISR group (n = 166) and a non-ISR (NISR) group (n = 271). The IL-6 gene promoter polymorphism at position -572 was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method. The serum IL-6 levels before and one day, five days and 180 days after PCI were determined by the radioimmunoassay method. RESULTS: ISR patients showed higher IL-6 serum levels than NISR patients before PCI ((324.42 ± 28.14) ng/L vs. (283.22 ± 47.30) ng/L, P < 0.001), and one day post-PCI IL-6 serum levels in the ISR group also showed a significantly higher level than in the NISR group (P < 0.001). Increased IL-6 after PCI persisted at a statistically significant level throughout the study in ISR patients, whereas IL-6 levels had normalized five days after the procedure in NISR patients. One day post-PCI serum IL-6 level was the most accurate marker for diagnosis of ISR, the area under the ROC curve being 0.927 (95%CI 0.878 - 0.977). The cut-off value for IL-6 to predict ISR was over 355.50 ng/L, with a sensitivity of 0.968 and a specificity of 0.865. There were no significant differences in frequencies of -572 genotype and allele between the two groups (P > 0.05). One day post-PCI IL-6 serum levels in patients with the G allele was significantly higher than in patients without the G allele ((366.99 ± 49.37) ng/L vs. (347.20 ± 55.30) ng/L, P < 0.05). In the ISR group, one day post-PCI serum levels of IL-6 in patients with the G allele was also significantly higher than that in patients without the G allele ((405.67 ± 26.56) ng/L vs. (375.69 ± 38.81) ng/L, P < 0.05). Multivariate Logistic regression analysis revealed positive correlations between male gender, one day post-PCI serum levels of IL-6, the pre-PCI degree of stenosis, the length of the target lesion stenosis, and restenosis; and there were negative correlations between the stent diameter, the diameter of the reference vessel before stent implantation and restenosis. CONCLUSIONS: IL-6 is an early post-PCI inflammatory cytokine, and one day post-PCI serum IL-6 level is an independent risk factor for restenosis. The frequencies of IL-6 gene -572 genotype and allele are not different between patients with and without ISR in a Chinese Tianjin Han population, but carrying the IL-6 -572G allele is likely to increase an individual's susceptibility to ISR by promoting serum IL-6 levels.

[Myocardial injury and inflammatory response after interventional therapy in children with congenital heart disease].

OBJECTIVE: To study myocardial injury and inflammatory response within 7 days after interventional therapy in children with congenital heart disease (CHD). METHODS: A total of 77 children with CHD, including 12 cases of ventricular septal defect (VSD), 14 cases of atrial septal defect (ASD), 14 cases of pulmonary stenosis (PS) and 37 cases of patent ductus arteriosus (PDA), were enrolled. The levels of myocardial enzyme (AST, CK and CKMB), cardiac troponin I (cTnI) and CRP in serum were measured before operation, immediately after operation, and 6 hrs, 24 hrs, 72 hrs and 7 days after operation. RESULTS: Serum AST levels in the VSD group were significantly higher than the other CHD groups immediately after operation, and 6 hrs and 24 hrs after operation (P<0.05). There were significant differences in serum CK and CKMB levels among the four CHD groups immediately and 6 hrs after operation (P<0.05), and the highest serum CK and CKMB levels were found in the VSD group. Serum CRP levels in the PDA group were significantly higher than the other CHD groups 72 hrs and 7 days after operation (P<0.05). Compared with before operation, serum AST levels increased significantly in all four CHD groups 6 and 24 hrs after operation groups (P<0.05). Serum CK and CKMB levels increased significantly in the VSD group immediately and 6 hrs after operation (P<0.05). Serum cTnI levels increased significantly in the VSD, PDA and PS groups immediately and 6 hrs after operation (P<0.05). The PDA group showed increased CRP levels 24 hrs, 72 hrs and 7 days after operation (P<0.05). CONCLUSIONS: Minor myocardial injury can be noted within 7 days after interventional therapy in children with CHD and mainly occurs between immediately and 24 hrs after operation. The injury is more significant in VSD cases. The interventional therapy does not cause significant inflammation.

[Relationship of interleukin-10 gene polymorphism with restenosis after percutaneous coronary intervention in Chinese].

OBJECTIVE: To investigate the relationship of interleukin-10 gene (IL-10) polymorphism and the serum IL-10 level with restenosis after percutaneous coronary intervention (PCI) in Tianjin Chinese Han population and study the effect of IL-10 gene polymorphism on serum IL-10 level. METHODS: Four hundred and thirty-seven patients who successfully underwent PCI with a follow-up angiography were divided into a restenosis group (n = 166) and non-restenosis group (n = 271). The IL-10 gene promoter polymorphism at position -592 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Meanwhile their serum IL-10 level before and 24 h after PCI was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) There was no significant difference in frequencies of -592 genotypes and alleles between the two groups (P > 0.05); (2) The 24 h post-PCI IL-10 serum level of restenosis group was significantly lower than that of the non-restenosis group [(82.67 ± 35.02) ng/L vs. (95.08 ± 32.26) ng/L, P < 0.05]; (3) The serum level of the A allele carriers (AA+AC) was significantly lower than that of the CC carriers [(86.13 ± 34.77) ng/L vs. (102.50 ± 27.52) ng/L, P < 0.05]; (4) In the restenosis group, the 24 h post-PCI serum level of IL-10 in the A allele carriers was also significantly lower than that in those without the A allele [(78.51 ± 34.09) ng/L vs. (102.19 ± 33.66) ng/L, P < 0.05]; (5) Logistic regression analysis revealed positive correlations between acute coronary syndrome patients, pre-PCI degree of stenosis, length of target stenosis lesion and restenosis (OR = 5.90, 1.86, 2.83 respectively); and there were negative correlations between 24 h post-PCI serum level of IL-10, the stent diameter, the diameter of reference vessel before stent implantation and restenosis(OR = 0.99, 0.70, 0.46 respectively). CONCLUSION: (1) The IL-10 gene -592 C/A polymorphism was not associated with restenosis in the Tianjin Chinese Han population; (2) IL-10 is an early post-PCI inflammatory cytokine, 24 h post-PCI serum IL-10 level was an independent predictive factor for restenosis, the IL-10 A allele carriers may have increased incidence of in-stent restenosis (ISR) by reducing the serum IL-10 levels.