Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

Serum Anion Gap Level Predicts All-Cause Mortality in Septic Patients: A Retrospective Study Based on the MIMIC III Database.

PURPOSE: Sepsis is a significant threat in the intensive care unit (ICU) worldwide because it has high morbidity and mortality rates. Early recognition and diagnosis of sepsis are essential for the prevention of adverse outcomes. The present study aimed to quantitatively assess the association between serum anion gap (AG) levels and 30- and 90-day all-cause mortality among sepsis patients. METHODS: Clinical data of patients diagnosed with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between serum AG levels and all-cause mortality. A receiver operating characteristic (ROC) curve was drawn to quantify the efficacy of using the serum AG level to predict all-cause mortality. RESULTS: A total of 3811 patients were included in the study. The Kaplan-Meier curves showed that patients with higher serum AG levels had a shorter survival time than those with lower levels. Serum AG levels were found to be highly effective in predicting all-cause mortality secondary to sepsis (30-day: AUROC = 0.703; 90-day: AUROC = 0.696). The Cox regression model further indicated that the serum AG level was an independent risk factor for 30- and 90-day mortality in sepsis (HR 3.44, 95% CI 2.97-3.99 for 30-day; HR 3.17, 95% CI 2.76-3.65 for 90-day, P < 0.001 for both). CONCLUSIONS: High serum AG may be considered as an alternative parameter for predicting the death risk in sepsis when other variables are not immediately available. Prospective large-scale studies are needed to support its predictive value in the clinic.

The prevalence of disability and associated factors among community adults in the baseline of CHCN-BTH Cohort Study.

BACKGROUND: Disability was a major public health problem in China. However, the prevalence of disabilities in community-dwelling adults and their relationships to chronic physical conditions were unclear. We aimed to estimate the prevalence of disabilities and associated factors among a large community-based cohort in China. METHODS: Participants who were local permanent residents aged 18 years or above and completed the disability assessments were selected from the Cohort study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Disability was assessed using five questions about impairments and activity limitations based on the International Classification of Functioning (ICF), Disability and Health. Univariate, multivariate and multilevel logistic regressions were conducted to estimate the associations between disabilities and associated factors. RESULTS: Totally, 12,871 community-dwelling adults completed the survey. Among of them, 12.9% (95% CI: 12.3%-13.5%) reported having any disability. The prevalence of any disability was significantly higher in participants who were older age, widowed, retired and smokers, had higher BMI, average monthly income < 5000 RMB, lower education level, lower physical exercise frequency and heavy physical labor. Multilevel logistic regressions showed that there were significant associations between disabilities with chronic physical conditions, especially in the vision impairment with lower back pain, and hearing impairment as well as difficulty walking without special equipment with injuries. CONCLUSIONS: Many Chinese adults suffered from disabilities. Sustained efforts should be made to develop specific population-based health promotion and prevention programs for disabilities in China. TRAIL REGISTRATION: ChiCTR1900024725 (25/07/2019).

Combined effects of ambient air pollution and PM2.5 components on renal function and the potential mediation effects of metabolic risk factors in China.

Growing evidence links long-term air pollution exposure with renal function. However, little research has been conducted on the combined effects of air pollutant mixture on renal function and multiple mediation effects of metabolic risk factors. This study enrolled 8996 adults without chronic kidney disease (CKD) at baseline from the CHCN-BTH cohort study. Three-year exposure to air pollutants [particulate matter ≤ 2.5 µm (PM2.5), PM10, PM1, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)] and PM2.5 components [black carbon (BC), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-) and organic matter (OM)] were assessed using well-validated machine learning methods. Linear mixed models were applied to investigate the associations between air pollutants and estimated glomerular filtration rate (eGFR). Quantile G-computation was used to assess the combined effects of pollutant mixtures. Causal mediation analysis and Bayesian mediation analysis were employed to estimate the mediation effects of metabolic risk factors. An interquartile range increases in BC (-0.256, 95 %CI: -0.331, -0.180) and OM (-0.603, 95 %CI: -0.810, -0.397) were significantly associated with eGFR decline; while O3 (1.151, 95 %CI: 0.813, 1.489), PM10 (0.721, 95 %CI: 0.309, 1.133), NH4+ (0.990, 95 %CI: 0.638, 1.342), and NO3- (0.610, 95 %CI: 0.405, 0.815) were associated with higher eGFR. The combined effect of the PM2.5 component mixture was found to be associated with lower eGFR (-1.147, 95 % CI: -1.456, -0.839), with OM contributing 72.4 % of the negative effect. Univariate mediation analyses showed that high-density lipoprotein (HDL) mediated 7.1 %, 6.9 %, and 6.1 % effects of O3, BC, and OM, respectively. However, these mediation effects were not significant in Bayesian mediation analysis. These findings suggest the effect of the PM2.5 component mixture on eGFR decline and the strong contribution of OM. Metabolic risk factors may not mediate the effects of air pollutants. Further study is warranted to clarify the potential mechanisms involved.

The mediation effect of lipids, blood pressure and BMI between air pollutant mixture and atherosclerotic cardiovascular disease: The CHCN-BTH cohort study.

BACKGROUND: The combine effect of air pollutant mixture on atherosclerotic cardiovascular disease (ASCVD) remain undefined. This study aims to explore the association between long-term exposure of air pollutants and ASCVD, focusing on the mediating role of lipids, blood pressure and BMI. METHODS: This study was based on the CHCN-BTH cohort study. The annual concentrations of air pollutants and PM2.5 constituents were sourced from in the Tracking Air Pollution in China (TAP) and ChinaHighAirPollutants (CHAP) datasets from 2014 to 2019. A Cox mixed-effects model was used to investigate the associations between long-term exposure of air pollutants and ASCVD. The combined impact of the air pollutant mixture was assessed using Quantile g-Computation. Stratified, sensitivity, and mediation analyses were conducted. RESULTS: A total of 27,134 participants aged 18-80 were recruited in the present study. We found that each IQR increase of PM2.5, PM1, NO2, O3, BC, SO42-, and OM were significantly associated with the incidence of ASCVD, the hazard ratios (HRs) and 95 % confidence interval (CI) were 1.55 (1.35, 1.78), 1.46 (1.27, 1.67), 1.30 (1.21, 1.39), 1.66 (1.41,1.95), 2.14 (1.63, 2.83), 1.65 (1.25, 2.17) and 1.92(1.52, 2.45), respectively. The combined effect of air pollutant mixture on ASCVD was 1.79 (1.46, 2.20), PM2.5 contributed 83.3 % to this combined effect. Mediation effect models suggested that air pollutants and ASCVD might be mediated through SBP, DBP, HDL-C, LDL-C, hsCRP and BMI (mediation proportion range from 1.3 % to 26.1 %), Notably, HDL-C played mediation roles of 11.3 % (7.0 %, 18.4), 26.1 % (17.7 %, 38.1 %) and 25.4 % (15.4, 47.7 %) in the effects of long-term exposure to PM2.5, PM1 and OM on ASCVD, respectively. CONCLUSIONS: Long-term, high-level air pollutant exposure was significantly associated with an elevated risk of ASCVD, particularly for PM2.5. Blood pressure, lipids and BMI, especially HDL-C, may mediate the effects of air pollutants exposure on ASCVD.

Impact of lipoprotein(a) level on cardiometabolic disease in the Chinese population: The CHCN-BTH Study.

BACKGROUND: The emergence of promising compounds to lower lipoprotein(a) [Lp(a)] has increased the need for a precise characterisation and comparability assessment of Lp(a)-associated cardiometabolic disease risk. This study aimed to evaluate the distribution of Lp(a) levels in a Chinese population and characterise the association with cardiometabolic diseases. METHODS: We assessed data from individuals from the Cohort Study on Chronic Diseases of the General Community Population in the Beijing-Tianjin-Hebei Region project. All Lp(a) measurements were performed in the same hospital. The cardiometabolic diseases considered were coronary heart disease (CHD), stroke, hypertension and type 2 diabetes (T2DM). RESULTS: A total of 25343 individuals were included in the study. The median level of Lp(a) was 11.9 mg/dl (IQR 5.9 to 23.7 mg/dl), and higher Lp(a) levels showed a significant concentration-dependent association with CHD risk. Individuals with Lp(a) levels lower than the 25th percentile were at increased risk of hypertension (OR: 1.15, 95% CI: 1.06-1.25) and T2DM (OR: 1.15, 95% CI: 1.03-1.28); however, Lp(a) levels were not significantly associated with stroke. The addition of Lp(a) levels to the prognostic model led to a marginal but significant C-index, integrated discrimination improvement and net reclassification improvement. CONCLUSIONS: In this large sample size study, we observed that elevated Lp(a) levels were significantly associated with CHD. Furthermore, we found that the lowest Lp(a) levels were also significantly associated with hypertension and T2DM. These results provide evidence for differential approaches to higher levels of Lp(a) in individuals with different cardiometabolic diseases.

[Clinical characteristics and analysis of IDS gene variant in a child with mucopolysaccharidosis type â ¡].

OBJECTIVE: To summarize the clinical features, laboratory examination and genetic analysis of a patient with mucopolysaccharidosis type Ⅱ (MPS Ⅱ). METHODS: Clinical manifestations, results of urine glycosaminoglycans (GAGs) and dermatan sulfate assay, metabolites related to MPS in peripheral blood leukocytes were analyzed. Meanwhile, the child and his mother were subjected to next-generation sequencing and Sanger sequencing. RESULTS: The boy has presented with global development delay, coarse facies, frequent upper-respiratory infections, hearing loss, indirect inguinal hernia, hepatosplenomegaly, and skeletal deformities. His urine GAGs were significantly elevated, and the urinary dermatan sulfate (DS) was positive. Meanwhile, the activity of idose-2-sulfatase was extremely reduced. The patient was found to harbor a hemizygote c.676C>G (p. His226Asp) missense variant in exon 5 of IDS gene, for which his mother was heterozygous. CONCLUSION: The novel c.676C>G variant of the IDS gene probably underlay the MPS Ⅱ in this child. Genetic testing combined with enzymatic analysis can enable effective diagnosis and classification of MPS.

[Establishment of a system for regulating the gene expression of embryonic mouse cerebral cortex neural stem cells by in utero electroporation]. / å­å®«å† ç”µç©¿å­”æ³•è°ƒæŽ§é¼ èƒšå¤§è„‘çš®è´¨ç¥žç»å¹²ç»†èƒžåŸºå› è¡¨è¾¾ä½“ç³»çš„å»ºç«‹.

OBJECTIVES: To establish a system for regulating the gene expression of embryonic mouse cerebral cortex neural stem cells (NSCs) using in utero electroporation (IUE). METHODS: At embryonic day 14.5, the mouse cerebral cortex NSCs were electro-transfected with the pCIG plasmid injected into the ventricle of the mouse embryo. At embryonic day 16.5 or day 17.5, embryonic mouse brain tissues were collected to prepare frozen sections. Immunofluorescence staining was used to observe the proliferation, apoptosis, division, directional differentiation, migration, and maturation of NSCs. RESULTS: The differentiation of NSCs into intermediate progenitors, the proliferation and apoptosis of NSCs, and the morphological development of radial axis of radial glial cells were observed at embryonic day 16.5. The differentiation of NSCs into neurons in layers V-VI of the cerebral cortex, the migration of NSCs to the lateral cerebral cortex, the development of dendrites of migrating neurons, and the maturation of neurons were observed at embryonic day 17.5. CONCLUSIONS: The system for regulating the gene expression of embryonic mouse cerebral cortex NSCs can be established using IUE, which is useful for the study of neural development related to the proliferation, apoptosis, division, directional differentiation, migration and maturation of NSCs in the cerebral cortex.

Association of long-term exposure to ambient particulate pollution with stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline and cardiovascular disease: The CHCN-BTH cohort study.

BACKGROUND: Evidence regarding the effects of ambient air pollution on new stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline remains sparse. OBJECTIVES: To investigate the association of long-term exposure to ambient PM2.5 with stage 1 hypertension and to explore the mediating and modifying effects of PM2.5 on cardiovascular disease (CVD). METHODS: A total of 32,135 participants aged 18-80 years were recruited in 2017. The three-year (2014-2016) average PM2.5 concentrations were assessed by a spatial statistical model. Blood pressure (BP) was divided into four categories according to the 2017 ACC/AHA Hypertension Guideline: normal BP (SBP<120 mmHg and DBP<80 mmHg), elevated BP (SBP 120-129 mmHg and DBP<80 mmHg), stage 1 hypertension (SBP 130-139 mmHg or DBP 80-89 mmHg), and stage 2 hypertension (SBP≥140 mmHg or DBP≥90 mmHg or taking antihypertensive medications). The associations of PM2.5 with BP categories were estimated by two-level generalized linear mixed models. Analyses stratified by age, mediation and interaction analyses of PM2.5 and stage 1 hypertension with CVD were performed. RESULTS: We detected a positive significant association between long-term exposure to PM2.5 and stage 1 hypertension. Compared to normal BP, the OR was 1.05 (95% CI: 1.02, 1.08) per 10 µg/m3 increase in PM2.5. The association was stronger than that of elevated BP but weaker than that of stage 2 hypertension. Stage 1 hypertension only partially mediated the association between PM2.5 and CVD, and the mediation proportions ranged from 1.55% to 11.00%. However, it modified the association between PM2.5 and CVD, which was greater in participants with stage 1 hypertension (OR: 1.66; 95% CI: 1.43, 1.93) than in participants with normal BP (OR: 1.32; 95% CI: 1.11, 1.57), with Pinteraction<0.001. In the analysis stratified by age, the above associations were age-specific, and significant associations were only observed in the young and middle-aged (<60 years) groups. CONCLUSIONS: Long-term exposure to ambient PM2.5 was significantly associated with stage 1 hypertension. This earlier stage of hypertension may be a trigger BP range for adverse effects of air pollution in the development of hypertension and CVD, especially in young and middle-aged individuals.

Association study of fasting blood glucose and salt sensitivity of blood pressure in community population: The EpiSS study.

BACKGROUND AND AIMS: To evaluate the association between fasting blood glucose (FBG) and salt sensitivity of blood pressure (SSBP). METHODS AND RESULTS: This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. Subjects were classified into salt sensitive (SS) and salt resistant groups according to blood pressure (BP) changes during the modified Sullivan's acute oral saline load and diuresis shrinkage test. Multivariate logistic and linear regression were used to evaluate associations between FBG with SS or BP changes. A total of 2051 participants were included in the analyses with 581 (28.33%) for SS. Multiple analysis showed that for every interquartile range increase in FBG, the OR (95%CI) for SS was 1.140 (1.069, 1.215), ß (95%CI) for mean arterial pressure change (ΔMAP1), systolic and diastolic BP changes during saline load were 0.421 (0.221, 0.622), 0.589 (0.263, 0.914) and 0.340 (0.149, 0.531), respectively. Compared to the lowest FBG quartile (Q1), the OR (95%CI) for SS in Q3 and Q4 were 1.342 (1.014, 1.776) and 1.577 (1.194, 2.084), respectively. Compared to subjects with normal FBG, the ß (95%CI) for ΔMAP1 was 0.973 (0.055, 1.891) in subjects with impaired FBG, and was 1.449 (0.602, 2.296) in patients with diabetes mellitus. Stratified analyses showed significant and stronger associations between FBG with SSBP in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers. CONCLUSION: Our findings suggest FBG is an independent, dose-dependent associated factor for SSBP, and prevention of SS focusing on controlling FBG elevation in the early stage is important.

Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study.

BACKGROUND: There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity. METHODS: Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies. RESULTS: Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901-0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941-0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949-1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950-0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950-1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981-1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960-1.009; P = 0.214). CONCLUSIONS: This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.

Associations of CYP2B6 genetic polymorphisms with Hirschsprung's disease in a southern Chinese population.

BACKGROUND: Hirschsprung's disease (HSCR) is an enteric nervous system birth defect partially caused by a genetic disorder. Single-nucleotide polymorphisms (SNPs) of the cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene are reported to be associated with HSCR. METHODS: We evaluated the association of rs2054675, rs707265, and rs1042389 with HSCR susceptibility in southern Chinese children including 1470 HSCR patients and 1473 controls using the TaqMan SNP Genotyping Assay. RESULTS: rs2054675 C allele and the rs707265 G allele were risk SNPs for total colonic aganglionosis (OR = 1.82, 95% CI 1.29 ~ 2.55, P_adj < 0.001 and OR = 0.68, 95% CI 0.48 ~ 0.97, P_adj = 0.034). These results suggested that CYP2B6 rs2054675 and rs707265 polymorphisms were associated with increased susceptibility to the severe HSCR subtype in southern Chinese children. CONCLUSION: We suggest that CYP2B6 rs2054675 and rs707265 polymorphisms are associated with increased susceptibility to the severe HSCR subtype in southern Chinese children.

Physical and neuropsychological development of children with Citrin deficiency. / Citrinç¼ºé™·ç— æ‚£å„¿ä½“æ ¼å’Œç¥žç»å¿ƒç†å‘è‚²çŠ¶å†µ.

OBJECTIVES: To study the physical and neuropsychological development of children with Citrin deficiency (CD). METHODS: A total of 93 children, aged 1.9-59.8 months, who were diagnosed with CD by SLC25A13 gene analysis in the First Affiliated Hospital of Jinan University from August 2010 to August 2015, were enrolled as subjects. A retrospective analysis was performed for their birth condition and physical growth and neuropsychological development indices. Among these children, 7 underwent physical measurement and neuropsychological development assessment within 1 year old and after 1 year old, and therefore, a total of 100 cases were included for analysis. RESULTS: For the 93 children with CD, the incidence rate of failure to thrive was 25% (23 children) and the proportion of small for gestational age was 47% (44 children). For the 100 cases of CD, the incidence rates of growth retardation, underweight, emaciation, overweight, and microcephalus were 23% (23 cases), 14% (14 cases), 4% (4 cases), 8% (8 cases), and 9% (9 cases), respectively. The incidence rate of neuropsychological developmental delay was 25% (25 cases), and the incidence rates of development delay in the five domains of adaptability, gross motor, fine motor, language, and social ability were 7% (7 cases), 15% (15 cases), 7% (7 cases), 9% (9 cases), and 7% (7 cases), respectively. CONCLUSIONS: Physical and neuropsychological developmental delay can be observed in children with CD, and physical and neuropsychological development should be regularly assessed.

Associations between ambient air pollution and mortality from all causes, pneumonia, and congenital heart diseases among children aged under 5 years in Beijing, China: A population-based time series study.

BACKGROUND: Previous studies have mainly focused on the associations between particulate matters and infant mortality. However, evidence regarding the associations between gaseous pollutants and mortality among children aged <5 years remains sparse. OBJECTIVES: The aim of this study was to investigate the associations between ambient air pollution and death among children aged <5 years in Beijing, China, and explore the impact of age, gender and specific causes of death on these associations. METHODS: Concentrations of ambient air pollution and the number of deaths among children aged <5 years in Beijing from January 2014 to September 2016 were extracted from authoritative electronic databases. The associations were estimated for a single-month lag from the current month up to the previous 5 months (lag0-lag5) and moving averages of the current and previous months (lag01-lag05) using generalized additive Poisson regression (adjusted for time trends, season, meteorological variables and holidays). Subgroup analyses related to age, gender and specific diseases were performed. Two-pollutant models were used to evaluate the possible role of single pollutants. RESULTS: Sulfur dioxide (SO2), nitrogen dioxide (NO2) and carbon monoxide (CO) demonstrated the strongest associations with death among children aged <5 years at lag0, and the estimates decreased or even turned negative with the increasing lag periods. For an interquartile range increase in SO2, NO2 and CO at lag0, the odds ratios (OR) were 1.332 (95% CI 1.152-1.539), 1.383 (95% CI 1.113-1.718) and 1.273 (95% CI 1.028-1.575). However, CO lost significance after adjusting for SO2 and NO2, and PM2.5 gained significance (OR 1.548, 95% CI 1.061-2.258) after adjusting for PM10. The ORs for SO2 and NO2 remained the most stable across all two-pollutant models. The associations for children aged 1-5 years were stronger than those reported for infants at lag0 but lower at the other lag months. The pollutant associations were stronger for congenital heart disease-related death than overall and pneumonia-related death. We did not find significant differences in terms of gender. CONCLUSION: Exposure to air pollution may increase the incidence of death among children aged <5 years. SO2 and NO2 may be the most stable pollutants reflecting associations between air pollution and death, deserving further attention. Children with congenital heart diseases are more susceptible to air pollution. Therefore, it is urgent to implement the clean air targets established by WHO and reduce the exposure of children to air pollution.

[Mutation analysis of NTRK1 gene in a family affected with congenital insensitivity to pain with anhidrosis].

OBJECTIVE: To screen for mutations of NTRK1 gene in a Chinese family affected with congenital insensitivity to pain with anhidrosis (CIPA). METHODS: Genomic DNA was extracted from the proband and her family members. All of the 17 exons and intron-exon boundaries of the NTRK1 gene were analyzed by direct Sanger sequencing. For the deletional mutation, the PCR products were subjected to T-A cloning and sequencing to verify the mutation. RESULTS: NTRK1 gene analysis revealed that proband has carried a c.1786C>T (p.Arg596*) nonsense mutation inherited from her mother and a novel deletional mutation c.1928-2028+23del from her father. Her elder brother only carried the deletional mutation. CONCLUSION: The diagnosis of CIPA relied on typical clinical symptoms of no pain, anhidrosis and intellectual disability and detection of the biallelic NTRK1 mutations. The novel deletional mutation has enriched the spectrum of NTRK1 mutations.

[Evaluation of white matter myelination in preterm infants using DTI and MRI].

OBJECTIVE: To investigate the features of white matter myelin development in preterm infants using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: A total of 31 preterm infants with a gestational age of ≤32 weeks and a birth weight of <1 500 g were enrolled. According to head MRI findings, these infants were divided into preterm group with brain injury (12 infants) and preterm group without brain injury (19 infants). A total of 24 full-term infants were enrolled as control group. Head MRI and DTI were performed at a gestational age or corrected gestational age of 37-40 weeks. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured for the same regions of interest in the three groups. RESULTS: The preterm group with brain injury showed a significantly lower FA value of the posterior limb of the internal capsule than the preterm group without brain injury and full-term control group (P<0.05). The preterm groups with and without brain injury showed significantly lower FA values of frontal white matter and lenticular nucleus than the full-term control group (P<0.05). The FA value of occipital white matter showed no significant differences among the three groups (P>0.05). Compared with the full-term control group, the preterm groups with and without brain injury showed significantly higher ADC values of the posterior limb of the internal capsule, lenticular nucleus, occipital white matter, and frontal white matter (P<0.05). CONCLUSIONS: After brain injury, preterm infants tend to develop disorder or delay of white matter myelination in the posterior limb of the internal capsule. At a corrected full-term gestational age, the preterm infants with and without brain injury have a lower grade of maturity in periventricular white matter and grey matter than full-term infants.

Using phlebotomy to remove a difficult peripherally inserted central catheter insertion and removal in very low birth weight infants: case report of a rare complication.

Background: A peripherally inserted central catheter (PICC) is an important way to supply long-term intravenous infusion or parenteral nutrition for premature infants, especially very low birth weight (VLBW) infants. PICC removal difficulties occur mostly during use. It is rare to have difficulty removing a PICC due to reverse folding during catheterization. We presented a case to explore the nursing experience of caring for a VLBW infant with difficult PICC removal. Case Description: A 30-week, 1,240-g infant, suffered a difficult PICC removal during the catheterization adjustment process. The X-ray images showed that the tip of the catheter was bent at the elbow joint and formed three abnormal bends in the blood vessel. The result was that the catheter was removed by a multidisciplinary team, and the reasons for the difficulty were analyzed. We used multidisciplinary team collaboration to solve a clinical problem. First, we analyzed the possible causes of a difficult removal by consulting PICC nurses, vascular interventional surgeons, and venous specialist nurses. Second, we used nonsurgical treatment methods to try to solve the problem. Finally, the catheter was completely removed using phlebotomy. Healing of wound and the growth of blood vessel are both well. Conclusions: In neonates, PICC may have obstacles in insertion and removal, methods such as posture changes, wet and hot compresses, and local massage can help. Multidisciplinary cooperation can improve the success rate of removal with minimal trauma. Individualized analysis of causes and measures are key steps to solve the difficulty of PICC insertion and removal.

Prospective evaluation of term neonate brain damage following preceding hypoxic sentinel events using enhanced T2* weighted angiography (eSWAN).

PURPOSE: To evaluate the brain damage of term neonates with evidence of a preceding hypoxic sentinel event using eSWAN prospectively. METHODS: The study was approved by the institutional research ethics committee. Among the neonates who were examined during the first 8 days after birth with conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and eSWAN, 39 neonates with a preceding acute hypoxic sentinel event were divided into two groups: the hypoxic ischaemic encephalopathy (HIE) group and the high-risk group. Twenty-five neonates were normal control subjects. Conventional MRI, DWI, and T2* and R2* maps from eSWAN were assessed. T2* and R2* values from T2* and R2* maps were calculated in predefined regions in the HIE and high-risk groups and then compared with those in control subjects. RESULTS: The neonates in the HIE and high-risk groups showed a high percentage of cerebral oedema and periventricular white-matter (PWM) lesions. Cerebral oedema and haemorrhagic lesions of PWM were more highly visible on the T2* map compared with conventional MRI: cerebral oedema was illustrated as a high T2* area and haemorrhagic lesions had a significantly lower T2* on the T2* map. Lower R2* values of lentiform nuclei (LN) and a higher T2* and lower R2* of frontal white matter (FWM) were found in neonates in the HIE group relative to those of normal controls. The T2* value of LN in the high-risk group was higher than that of the normal controls. CONCLUSIONS: The T2* map from eSWAN is useful in detecting cerebral oedema and haemorrhagic lesions of PWM in neonates. The measurement of T2* and R2* values is helpful in assessing the LN and FWM damage in neonates following a hypoxic sentinel event.

Association of long-term exposure to air pollutant mixture and incident cardiovascular disease in a highly polluted region of China.

Despite growing evidence that links long-term air pollution exposure to cardiovascular disease (CVD), the combined effects of air pollutants and particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) components are still limited. A prospective cohort study was performed based on the Cohort Study on Chronic Disease of the Community Natural Population in the Beijing-Tianjin-Hebei Region (CHCN-BTH) to assess the association of long-term air pollutants with incident CVD and the combined effect of the air pollutants mixture among 26,851 adults. Three-year residential exposure to air pollutants (PM2.5, O3, PM10, PM1, NO2, SO2 and CO) and PM2.5 components [black carbon (BC), NH4+, SO42-, NO3- and organic matter (OM)] were calculated based on well-validated models. Proportional hazard models were applied to assess the association of air pollutants with incident CVD. Quantile g-Computation was used to examine the combined effect of the pollutant mixture. During the 56,090 person-years follow-up, 629 participants reported incident CVD. Adjusted hazard ratios with 95% confidence intervals (CIs) of CVD per interquartile range increase in O3, PM2.5, PM1, NO2, BC, and OM concentrations were 4.52 (95%CI: 2.61, 7.83), 2.39 (95%CI: 1.83, 3.13), 2.37 (95%CI: 1.20, 4.70), 1.36 (95%CI: 1.19, 1.56), 3.84 (95%CI: 2.38, 6.18), and 3.07 (95%CI: 2.01, 4.69), respectively. In multi-pollutant models, the combined effect of air pollutant mixture on incident CVD was 2.37 (95%CI: 2.30, 2.44). PM2.5 and O3 contributed 54.3% and 44.5% of the combined effect of the air pollutant mixture, respectively. After using PM2.5 components instead of PM2.5 as part of the mixture, OM drove 55.2% of the combined effect. The findings indicated associations of air pollutant mixtures with CVD incidence. PM2.5 (especially OM) and O3 might strongly contribute to air pollutant mixtures that lead to incident CVD.

Association of Serum Metabolites and Salt Sensitivity of Blood Pressure in Chinese Population: The EpiSS Study.

BACKGROUND: To identify novel metabolites associated with salt sensitivity of blood pressure (SSBP) in Chinese Han population. METHODS: A case-control study was conducted with 25 salt sensitive (SS) and 26 salt resistant (SR) participants, which was selected from the Systems Epidemiology Study on Salt Sensitivity of Blood Pressure (EpiSS) study. The modified Sullivan's acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was conducted to identify SS. Untargeted, ultra-high performance liquid chromatograph-high resolution mass spectrometer (UPLC-HRMS) was conducted and orthogonal partial least squares-discriminate analysis (OPLS-DA) and multivariable logistic regression model were used to screen the metabolites related to SS, mixed linear regressions models were used to examined the association of SSBP with metabolites during saline load period and diuresis shrinkage period. Receiver operating characteristic (ROC) curve analysis was performed. The area under the curve's (AUC) sensitivity and specificity were calculated to identified metabolites biomarkers for SS. RESULTS: There were 39 differentially expressed metabolites (DE-metabolites) between SS and SR. Thirty-five and four of DE-metabolites were inversely or positively associated with SS, respectively. Four biochemical pathways demonstrated significant enrichment for identified metabolites. In single-metabolite analyses, L-Glutamine displayed the best diagnostic performance (AUC = 0.88, 95% CI: 0.78-0.97). In multi-metabolites analyses, L-Glutamine + Cholesterol ester 22:5n6 combination showed the best diagnostic performance (AUC = 0.96, 95% CI: 0.91-1.00). Adjusted for traditional risk factors, L-Glutamine and Cholesterol ester 22:5n6 explained an additional 38.3% of SS susceptibility. CONCLUSIONS: This study provide potential evidence for clarifying the mechanism of SS and provide novel biological insights into salt sensitive hypertension.