Duration-specific association between plasma IGFBP7 levels and diabetic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients. DESIGN: A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively. RESULTS: Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06-5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7. CONCLUSION: IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.

Association between human blood metabolome and the risk of pre-eclampsia.

Pre-eclampsia is a complex multi-system pregnancy disorder with limited treatment options. Therefore, we aimed to screen for metabolites that have causal associations with preeclampsia and to predict target-mediated side effects based on Mendelian randomization (MR) analysis. A two-sample MR analysis was firstly conducted to systematically assess causal associations of blood metabolites with pre-eclampsia, by using metabolites related large-scale genome-wide association studies (GWASs) involving 147,827 European participants, as well as GWASs summary data about pre-eclampsia from the FinnGen consortium R8 release data that included 182,035 Finnish adult female subjects (5922 cases and 176,113 controls). Subsequently, a phenome-wide MR (Phe-MR) analysis was applied to assess the potential on-target side effects associated with hypothetical interventions that reduced the burden of pre-eclampsia by targeting identified metabolites. Four metabolites were identified as potential causal mediators for pre-eclampsia by using the inverse-variance weighted method, including cholesterol in large HDL (L-HDL-C) [odds ratio (OR): 0.88; 95% confidence interval (95% CI): 0.83-0.93; P = 2.14 × 10-5), cholesteryl esters in large HDL (L-HDL-CE) (OR: 0.88; 95% CI: 0.83-0.94; P = 5.93 × 10-5), free cholesterol in very large HDL (XL-HDL-FC) (OR: 0.88; 95% CI: 0.82-0.94; P = 1.10 × 10-4) and free cholesterol in large HDL (L-HDL-FC) (OR: 0.89; 95% CI: 0.84-0.95; P = 1.45 × 10-4). Phe-MR analysis showed that targeting L-HDL-CE had beneficial effects on the risk of 24 diseases from seven disease chapters. Based on this systematic MR analysis, L-HDL-C, L-HDL-CE, XL-HDL-FC, and L-HDL-FC were inversely associated with the risk of pre-eclampsia. Interestingly, L-HDL-CE may be a promising drug target for preventing pre-eclampsia with no predicted detrimental side effects. The study consists of a two-stage design that conducts MR at both stages. First, we assessed the causality for the associations between 194 blood metabolites and the risk of pre-eclampsia. Second, we investigated a broad spectrum of side effects associated with the targeting identified metabolites in 693 non-preeclampsia diseases. Our results suggested that Cholesteryl esters in large HDL may serve as a promising drug target for the prevention or treatment of pre-eclampsia with no predicted detrimental side effects.

Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. METHODS AND RESULTS: This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores. CONCLUSIONS: An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Autonomic and cytokine mechanisms of acute electroacupuncture in a rodent model of functional dyspepsia.

BACKGROUND: Cytokines have been presumed to play an important role in the pathophysiology of functional dyspepsia (FD). Electroacupuncture (EA) has been used for FD treatment; however, its mechanisms remain largely unknown. This study aimed to (1) compare the plasma levels of cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10, in "FD" rats with normal control rats; (2) investigate whether EA, using chronically implanted electrodes, could inhibit the release of these cytokines; and (3) explore the correlation of cytokine levels with plasma norepinephrine (NE) levels and gastric emptying (GE). METHODS: A rodent model of FD was established via neonatal treatment with intragastric iodoacetamide. After 8 weeks, the rats were implanted with electrodes at acupoint ST36 for EA. The plasma levels of cytokines and NE were measured using enzyme-linked immunosorbent assay. We explored the correlations of cytokine levels with NE levels and GE. KEY RESULTS: (i) "FD" rats demonstrated increased levels of TNF-α, IL-1ß, and IL-6 (p < 0.05 each) compared with the control rats. (ii) EA significantly decreased the plasma levels of TNF-α, IL-1ß, and IL-6 in "FD" rats (p < 0.05 each) compared with sham EA. (iii) The plasma levels of NE were positively correlated with those of IL-6 (r = 0.86, p < 0.05) and IL-1ß (r = 0.81, p < 0.05), whereas NE levels and GE were negatively correlated with IL-10 levels (r = -0.870, p < 0.05 and r = -0.791, p < 0.05, respectively). CONCLUSIONS: EA inhibits the release of proinflammatory cytokines probably via the suppression of sympathetic activity in "FD" rats.

Growth and development of syphilis-exposed and -unexposed uninfected children during their first 18 months of life in Suzhou, China: a nested case-control study with propensity score matching.

Background: With the successful implementation of Prevention of Mother-to-Child Transmission (PMTCT) policies, the proportion of infants with exposure to both syphilis and antibiotic medication in utero has increased in China, but there is limited evidence about the early growth and development of such infants. Methods: We conducted a retrospective nested case-control study based on data from the China PMTCT program conducted in Suzhou from 2016 to 2021. Propensity score matching (PSM) was employed to extract 826 syphilis-exposed but uninfected (SEU) infants and 1,652 syphilis-unexposed uninfected (SUU) infants from a total of 712,653 infants. Maternal characteristics were collected through questionnaires, such as parity, age, education level, smoking and drinking habits during pregnancy. Infantile characteristics were retrieved from medical records or via questionnaires, such as gestational age, gender, mode of delivery, Apgar scores, birth weight and length, outdoor time, vitamin D intake, and feed pattern. Mixed effects models, adjusting for potential influencing factors, were used to investigate the early infantile growth pattern of SEU and SUU infants. All statistical analysis were conducted using R (version 4.2.0). Results: Length and weight were slightly higher in SEU infants than in the SUU infants at some time points (months 0 and 18 for length, p-values <0.05; months 0, 6, and 18 for weight, p < 0.05). In the mixed effects model, SEU group was found to be associated with higher weight [exponentiated beta exp.(ß) = 1.15, 95% Confidence Interval (CI) = 1.06, 1.25], length [exp(ß) = 1.42, 95% CI = 1.14, 1.77], and BMI z-score [exp(ß) = 1.09, 95% CI = 1.00, 1.19]. Conclusion: With the effective prevention of congenital syphilis under the PMTCT program, SEU infants have non-inferior growth patterns during their first 18 months of life compared with SUU controls in Suzhou, China.

Noninvasive electrical neuromodulation for gastrointestinal motility disorders.

INTRODUCTION: Gastrointestinal motility disorders are highly prevalent without satisfactory treatment. noninvasive electrical neuromodulation is an emerging therapy for treating various gastrointestinal motility disorders. AREAS COVERED: In this review, several emerging noninvasive neuromodulation methods are introduced, including transcutaneous auricular vagal nerve stimulation, percutaneous auricular vagal nerve stimulation, transcutaneous cervical vagal nerve stimulation, transcutaneous electrical acustimulation, transabdominal interference stimulation, tibial nerve stimulation, and translumbosacral neuromodulation therapy. Their clinical applications in the most common gastrointestinal motility are discussed, including gastroesophageal reflux disease, functional dyspepsia, gastroparesis, functional constipation, irritable bowel syndrome, and fecal incontinence. PubMed database was searched from 1995 to June 2023 for relevant articles in English. EXPERT OPINION: Noninvasive neuromodulation is effective and safe in improving both gastrointestinal symptoms and dysmotility; it can be used when pharmacotherapy is ineffective. Future directions include refining the methodology, improving device development and understanding mechanisms of action.

Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats.

Objectives: Sacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats. Methods: Experiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB). Key results: (1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p < 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p < 0.01); yet SNS normalized vagal activity. Conclusion: SNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRACT.

Ambient air pollutants in the first trimester of pregnancy and birth defects: an observational study.

OBJECTIVES: As current studies on the relationships between air pollutants exposure during the first trimester and birth defects were not fully elucidated, this study aimed to assess the association between selected air pollutants and birth defects. DESIGN: An observational study. PARTICIPANTS: We obtained 70 854 singletons with gestational age <20 weeks who were delivered at a large maternal and child healthcare centre in Wuhan, China. OUTCOME MEASURES: Birth defects data and daily average concentration of ambient particulate matter ≤10 µm diameter (PM10), PM ≤2.5 µm diameter (PM2.5), sulfur dioxide (SO2) and nitrogen dioxide (NO2) were obtained. Logistic regression analysis was applied to assess the association between maternal air pollutants exposure during first trimester and total birth defects, congenital heart defects (CHDs), limb defects and orofacial clefts with adjustments of potential covariates. RESULTS: There were a total of 1352 birth defect cases included in this study, with a prevalence of 19.08‰. Maternal exposed to high concentrations of PM10, PM2.5, NO2 and SO2 in the first trimester were significantly associated with elevated ORs of birth defects (ORs ranged from 1.13 to 1.23). Additionally, for male fetuses, maternal exposed to high PM2.5 concentration was associated with an elevated odd of CHDs (OR 1.27, 95% CI 1.06 to 1.52). In the cold season, the ORs of birth defects were significantly increased among women exposed to PM2.5 (OR 1.64, 95% CI 1.41 to 1.91), NO2 (OR 1.22, 95% CI 1.08 to 1.38) and SO2 (OR 1.26, 95% CI 1.07 to 1.47). CONCLUSIONS: This study showed unfavourable effects of air pollutants exposure during the first trimester on birth defects. Especially, the association between maternal PM2.5 exposure and CHDs was only observed among male fetuses, and stronger effects of PM2.5, NO2 and SO2 exposure on birth defects were observed in the cold season.

Prevalence of suicide ideation among HIV/AIDS patients in China: A systematic review and meta-analysis.

Objective: A systematic review and meta-analysis was performed to evaluate the prevalence of suicide ideation among HIV/AIDS patients in China. Methods: Systematic search of CNKI, Wanfang, China biology medicine database, Weipu, EMBASE, Web of science and PubMed for studies related to the suicide ideation of HIV/AIDS patients. The incidence of suicide ideation of HIV / AIDS patients in China was investigated by meta-analysis. Results: A total of 16 studies were included (n = 6,174). The incidence of suicidal ideation in HIV/AIDS patients was 30.6% (95%CI: 21.4-39.9%). The results of subgroup analysis showed that the incidence of suicidal ideation in male was 36.1%, which was higher than that in female (32.8%), homosexual patients (39.7%) higher than heterosexual patients (27.1%), 2013-2021 survey (35.2%) higher than 2003-2012 survey (26.5%), the unmarried patients (39.6%) were higher than the married patients (34.5%), the patients diagnosed >1 year (28.4%) were higher than the patients diagnosed <1 year (27.6%), and the depression patients (34.3%) were higher than patients without depression (20.5%) and CD4 cell counts ≤200 cells/ul group (20.6%) were higher than those in >400 cells/ul group (19.8%). Conclusion: The incidence of suicide ideation in HIV/AIDS patients in China is relatively high.

Aspirin 75 mg to prevent preeclampsia in high-risk pregnancies: a retrospective real-world study in China.

BACKGROUND: Several randomized clinical trials showed that aspirin could decrease the incidence of preeclampsia (PE) in women at high risk, but data from sources other than traditional clinical trials that investigating the preventive effect of aspirin 75 mg on PE is still lacking, especially in mainland China. We aimed to use Chinese real-world data to estimate the preventive effect of low-dose aspirin (LDA) on PE. METHODS: Clinical data of pregnant women who were at high risk of PE and had their first prenatal visit at the affiliated Taicang People's Hospital of Soochow University during November 31, 2018 and May 10, 2021 was retrospectively analyzed. Among the 266 included pregnant women, 115 individuals treated with aspirin 75 mg per day and the other 151 without such treatment were considered as the LDA group and the control group, respectively. RESULTS: In the LDA group, 64 (55.65%) of 115 pregnant women took aspirin before 16 weeks of gestation. Besides, 12 (10.43%) and 34 (22.52%) women developed PE in the LDA group and control group, respectively; the aspirin prophylaxis was associated with a lower risk of PE (odds ratio = 0.40, 95% confidence interval = 0.20-0.82, P = 0.0098). In addition, LDA is slightly more effective when initiated before 16 weeks of gestation or in those without chronic hypertension, when compared with their counterparts. CONCLUSION: Prophylaxis with 75 mg per day of aspirin in high-risk women resulted in a significantly lower incidence of PE than that in the control group.

Association between growth differentiation factor 15 levels and gestational diabetes mellitus: A combined analysis.

Objective: Gestational diabetes mellitus (GDM) is a common glucose metabolism disease occurs in pregnancy that affects both maternal and neonatal health. Recently, increasing studies have attached importance to the relationship between growth differentiation factor 15 (GDF-15) and GDM, but the results were inconclusive. Therefore, we conducted a meta-analysis to examine the association between GDF-15 and GDM. Materials and methods: A systematical search was performed in Gene Expression Omnibus (GEO), PubMed and Google Scholar till Oct 27, 2022. We first calculated the mean and standard deviation of GDF-15 expression levels from the included eligible datasets and articles. Then, a meta-analysis was conducted to depict the difference in GDF-15 mRNA or GDF-15 protein expression between case and control groups by using conservative random effect model. Moreover, the potential publication bias was checked with the aid of Begg's test and Egger's test. Finally, sensitivity analyses were performed by changing the inclusion criteria. Results: In summary, 12 GEO datasets and 5 articles were enrolled in our study, including 789 GDM patients and 1202 non-GDM pregnant women. It was found that the expression levels of GDF-15 mRNA and GDF-15 protein in late pregnancy were significantly higher in GDM patients compared with non-GDM pregnant women, with the standard mean difference (SMD) and 95% confidence interval (95% CI) of 0.48 (0.14, 0.83) and 0.82 (0.32-1.33), respectively. Meanwhile, a slightly weakened association between GDF-15 protein levels and GDM was also observed in the middle pregnancy, with SMD (95% CI) of 0.53 (0.04-1.02). Conclusion: In all, our results suggested that the expression levels of GDF-15 were significantly higher in GDM patients compared with non-GDM pregnant women, especially in the late pregnancy.

Pediatric body mass index trajectories and the risk of hypertension among adolescents in China: a retrospective cohort study.

BACKGROUND: The impact of pediatric body mass index (BMI) trajectories on the risk of adolescent hypertension (HTN) determined by three separate visits remains unclear. This longitudinal study aims to identify potential pediatric sex-specific BMI trajectories and to assess their associations with HTN and HTN subtypes. METHODS: Based on the Health Promotion Program for Children and Adolescents (HPPCA) in Suzhou, China, a total of 24,426 participants who had initial normal blood pressure (BP) and had at least four BMI measurements during 2012-2020 were included. HTN was defined as simultaneously having three separate visits of elevated BP in 2020. Latent class growth models were used to explore sex-specific BMI trajectories, whose associations with HTN and HTN subtypes were further examined by logistic regression. RESULTS: The incidence of HTN determined through three separate visits was 3.34%. Four trajectories were identified for both sexes: low BMI increasing, medium BMI increasing, high BMI increasing, and highest BMI increasing. Compared to the medium BMI increasing group, the odds ratio (95% confidential interval) for developing adolescent HTN of the low, high, and highest BMI increasing groups among boys were 0.54 (0.39, 0.75), 1.90 (1.44, 2.51), and 2.89 (1.90, 4.39), respectively; and the corresponding values for girls were 0.66 (0.48, 0.90), 2.30 (1.72, 3.09), and 4.71 (3.06, 7.26). Similar gradually elevated associations between different trajectories with isolated systolic hypertension, systolic and diastolic hypertension were observed. CONCLUSION: Current results emphasized the adverse effects of stable high BMI on HTN and the benefits of maintaining normal weight throughout childhood.

Relationship Between Plasma Growth Differentiation Factor 15 Levels and Complications of Type 2 Diabetes Mellitus: A Cross-sectional Study.

OBJECTIVE: Our aim in this study was to identify the associations between growth differentiation factor 15 (GDF15) and type 2 diabetes mellitus (T2DM) complications in a community-based population in China. METHODS: Based on a cross-sectional study registered in the National Basic Public Health Service for disease management of Changshu in China, a total of 1,689 T2DM patients were enrolled and tested further for plasma GDF15 levels. Macrovascular (cardiovascular disease and diabetic foot) and microvascular (diabetic kidney disease [DKD], diabetic retinopathy, and neuropathy) complications were evaluated. Logistic regression models were conducted to identify the associations of GDF15 with the risk of diabetes complications, and linear regression models were used to assess relationships between GDF15 and other clinical features. RESULTS: Overall, 459 of the 1,689 T2DM patients (27.18%) had complications. GDF15 levels were significantly higher in patients with any type of complication compared with their counterparts. With each standard deviation increase of base 10 logarithms of GDF15 (lg-GDF15), the risk of overall complications increased by 1.17-fold (95% confidence interval [CI], 1.03 to 1.32). In contrast to macrovascular complications, associations of GDF15 with microvascular complications appeared to be stronger (adjusted odds ratio [OR], 1.24; 95% CI, 1.08 to 1.43), especially for DKD (adjusted OR, 1.51; 95% CI, 1.19 to 1.93). Subgroup analyses showed that the strength of association between GDF15 and complications varied by distinct age and T2DM duration subgroups. Patients with 2 or more types of complications had higher levels of GDF15 than those with fewer types of complications. Also, linear relationships were identified between GDF15 and several liver and kidney function indices. CONCLUSION: Higher GDF15 levels were associated with T2DM complications, especially DKD. GDF15 may serve as a biomarker for monitoring the deterioration of T2DM.

Comparisons of tri-ponderal mass index and body mass index in discriminating hypertension at three separate visits in adolescents: A retrospective cohort study.

Objective: To estimate whether the new obesity indicator tri-ponderal mass index (TMI) has a better capacity to predict adolescent hypertension (HTN) and HTN subtypes at three separate blood pressure (BP) visits than the conventionally used body mass index (BMI). Methods: A total of 36,950 adolescents who had initial normal BP from 2012 to 2019 were included in Suzhou, China. HTN was defined as having three separate visits of elevated BP in 2020. The area under the receiver-operating characteristic curve (AUC), false-positive rate, false-negative rate, total misclassification rates, net reclassification improvement (NRI), and integrated discrimination improvement were calculated to compare the discriminative ability of HTN between BMI and TMI. Results: TMI had better predictive abilities than BMI among all of the participants when predicting HTN (difference in AUC = 0.019, 95% CI = 0.007-0.031; NRI = 0.067, 95% CI = 0.008-0.127) and isolated systolic hypertension (difference in AUC = 0.021, 95% CI = 0.005-0.036; NRI = 0.106, 95% CI = 0.029-0.183). The difference in prediction abilities between BMI and TMI was more obvious in the subgroup of age ≥16. Also, TMI outperformed BMI in predicting adolescent HTN in girls but not in boys. Conclusion: Compared with BMI, TMI may have a better predictive capacity for HTN, particularly in girls and older adolescents. TMI has the potential to be used as an effective predictor for HTN in clinic practice. Further studies are needed to verify the utility of TMI.

A cocktail of protective antibodies subverts the dense glycan shield of Lassa virus.

Developing potent therapeutics and effective vaccines are the ultimate goals in controlling infectious diseases. Lassa virus (LASV), the causative pathogen of Lassa fever (LF), infects hundreds of thousands annually, but effective antivirals or vaccines against LASV infection are still lacking. Furthermore, neutralizing antibodies against LASV are rare. Here, we describe biochemical analyses and high-resolution cryo-electron microscopy structures of a therapeutic cocktail of three broadly protective antibodies that target the LASV glycoprotein complex (GPC), previously identified from survivors of multiple LASV infections. Structural and mechanistic analyses reveal compatible neutralizing epitopes and complementary neutralization mechanisms that offer high potency, broad range, and resistance to escape. These antibodies either circumvent or exploit specific glycans comprising the extensive glycan shield of GPC. Further, they require mammalian glycosylation, native GPC cleavage, and proper GPC trimerization. These findings guided engineering of a next-generation GPC antigen suitable for future neutralizing antibody and vaccine discovery. Together, these results explain protective mechanisms of rare, broad, and potent antibodies and identify a strategy for the rational design of therapeutic modalities against LF and related infectious diseases.

Prevalence of hypertension and related risk factors among children and adolescents at three separate visits: A large school-based study in China.

Objective: We aimed to demonstrate characteristics of hypertension at three separate visits and its risk factors among children and adolescents based on a large school-based study in China. Materials and methods: Based on a large-scale ongoing monitoring program conducted in Suzhou, China, 59,679 children and adolescents aged 7-17 years from 60 public schools were enrolled during 2020 to 2021. Height, weight, and blood pressure (BP) were measured. Additional BP would be measured for hypertensive students at least 2 weeks later. Confirmed hypertension was defined as simultaneously BP meeting above or equal to 95th percentile for age, sex, and height at three separate visits. Odds ratio (ORs), and 95% CIs were calculated by logistic regression to identify risk factors for hypertension. Results: Prevalence of hypertension at three separate visits were 20.4, 6.3, and 3.1%, respectively. Prevalence of confirmed isolated systolic hypertension, isolated diastolic hypertension, and systolic and diastolic hypertension were 1.9, 0.3, and 0.9%, respectively. Hypertension prevalence for stages 1 and 2 were 2.6 and 0.6%. Different hypertension prevalence were found among various age and gender groups. Boys [OR, 1.137 (95% CI, 1.033-1.251)], high age [OR, 3.326 (95% CI, 2.950-3.751)], urban residents [OR, 1.579 (95% CI, 1.417-1.760)], high-socioeconomic status [OR, 1.156 (95% CI, 1.039-1.286)] and body mass index category including overweight [1.883 (95% CI, 1.665-2.129)], obesity [4.049 (95% CI, 3.625-4.523)], and thinness [OR, 0.457 (95% CI, 0.306-0.683)] were associated with confirmed hypertension. Conclusion: A single BP measurement would overestimate hypertension prevalence, about 3% Chinese children were hypertensive, early, and effective intervention around risk factors for hypertension should be taken.

The Exploration of Fetal Growth Restriction Based on Metabolomics: A Systematic Review.

Fetal growth restriction (FGR) is a common complication of pregnancy and a significant cause of neonatal morbidity and mortality. The adverse effects of FGR can last throughout the entire lifespan and increase the risks of various diseases in adulthood. However, the etiology and pathogenesis of FGR remain unclear. This study comprehensively reviewed metabolomics studies related with FGR in pregnancy to identify potential metabolic biomarkers and pathways. Relevant articles were searched through two online databases (PubMed and Web of Science) from January 2000 to July 2022. The reported metabolites were systematically compared. Pathway analysis was conducted through the online MetaboAnalyst 5.0 software. For humans, a total of 10 neonatal and 14 maternal studies were included in this review. Several amino acids, such as alanine, valine, and isoleucine, were high frequency metabolites in both neonatal and maternal studies. Meanwhile, several pathways were suggested to be involved in the development of FGR, such as arginine biosynthesis, arginine, and proline metabolism, glyoxylate and dicarboxylate metabolism, and alanine, aspartate, and glutamate metabolism. In addition, we also included 8 animal model studies, in which three frequently reported metabolites (glutamine, phenylalanine, and proline) were also present in human studies. In general, this study summarized several metabolites and metabolic pathways which may help us to better understand the underlying metabolic mechanisms of FGR.

Epigenetic remodeling by vitamin C potentiates plasma cell differentiation.

Ascorbate (vitamin C) is an essential micronutrient in humans. The severe chronic deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. From a micronutrient analysis, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique as other antioxidants failed to promote plasma cell differentiation. Ascorbate is especially critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. As a cofactor for epigenetic enzymes, ascorbate facilitates TET2/3-mediated DNA modification and demethylation of multiple elements at the Prdm1 locus. DNA demethylation augments STAT3 association at the Prdm1 promoter and a downstream enhancer, thus ensuring efficient gene expression and plasma cell differentiation. The results suggest that an adequate level of ascorbate is required for antibody response and highlight how micronutrients may regulate the activity of epigenetic enzymes to regulate gene expression. Our findings imply that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.

Application of metabolomics in intrahepatic cholestasis of pregnancy: a systematic review.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a severe idiopathic disorder of bile metabolism; however, the etiology and pathogenesis of ICP remain unclear. AIMS: This study comprehensively reviewed metabolomics studies related to ICP, to help in identifying the pathophysiological changes of ICP and evaluating the potential application of metabolomics in its diagnosis. METHODS: Relevant articles were searched through 2 online databases (PubMed and Web of Science) from January 2000 to March 2022. The metabolites involved were systematically examined and compared. Pathway analysis was conducted through the online software MetaboAnalyst 5.0. RESULTS: A total of 14 papers reporting 212 metabolites were included in this study. There were several highly reported metabolites: bile acids, such as glycocholic acid, taurochenodeoxycholic acid, taurocholic acid, tauroursodeoxycholic acid, and glycochenodeoxycholic acid. Dysregulation of metabolic pathways involved bile acid metabolism and lipid metabolism. Metabolites related to lipid metabolism include phosphatidylcholine, phosphorylcholine, phosphatidylserine, sphingomyelin, and ceramide. CONCLUSIONS: This study provides a systematic review of metabolomics of ICP and deepens our understanding of the etiology of ICP.