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BACKGROUND: Nutrient-rich cheese supplements were demonstrated to have improvements in markers of sarcopenia in healthy elders. However, the potential effects of cheese in individuals with possible sarcopenia remain unknown. METHOD: This 90-day randomized controlled trial (RCT) included 68 women aged 60-80 years with possible sarcopenia in China, who were randomly assigned to three groups: Control group (CG), Original cheese group (OG: 9.0 g protein; 322.8 mg calcium), and Golden cheese group (GG: 12.7 g protein; 802.1 mg calcium). OG and GG were instructed to consume their habitual diet along with 4 slices of supplied cheese, while CG was directed to maintain their usual dietary habits. Face-to-face interviews, anthropometric measurements, and blood sample collection were conducted at baseline, midway (60 days), and the end of the trial. RESULT: At the end of the trial, the primary outcome, changes of Skeletal Muscle Mass Index (SMI) were found to be higher in OG (0.18 ± 0.02 kg/m2) and GG (0.14 ± 0.02 kg/m2) compared to CG (0.09 ± 0.02 kg/m2). The secondary outcome, changes of handgrip strength were higher in GG (1.82 ± 4.16 kg) than CG (-0.61 ± 3.78 kg). There were no significant differences in makers for muscle function between three groups (P > 0.05). In the self-comparison, Creatinine/Cystatin C significantly increased in both OG and GG. In addition, OG had a significant increase in changes of free and total carnitine compared to CG. CONCLUSION: Both golden and original cheese supplementation enhanced muscle strength and mass in older women with possible sarcopenia. The mechanism behind this effect may be linked to muscle cell energy metabolism. TRIAL REGISTRATION: The present study was registered in the Chinese Clinical Trial Registry with the registration number ChiCTR2300078720 (retrospectively registered, 20231215).
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BACKGROUND: Limited studies explored the association between ultra-processed food (UPF) consumption and rheumatoid arthritis (RA). OBJECTIVE: This study aimed to examine the association between UPF consumption and RA risk and explore the potential mediating effects of RA-related biomarkers. METHODS: This retrospective cohort study included 207,012 participants without RA at recruitment and completed 24 h dietary recalls. UPF was defined based on the NOVA classification system. Incident RA was ascertained using the International Classification of Diseases version 10. Cox regression models were used to examine the association between UPF consumption and the incidence of RA. Additionally, mediation analyses were conducted to evaluate the contribution of biomarkers related to the lipid profile, systemic inflammatory factors, serum liver enzymes, and glucose metabolism to the observed associations. RESULTS: The mean [standard deviation (SD)] age of the participants at recruitment was 56.08 (7.95) years. During a median follow-up of 12.24 (interquartile range: 11.66-13.03) years, 1,869 RA events were recorded. Compared with the lowest quintile of UPF consumption (weight percentage of the UPF), the adjusted hazard ratio (HR) of RA in the highest quintile was 1.17 (95% CI: 1.01, 1.36). There was a 6% elevated risk of RA incidence per SD increase in UPF intake (HR: 1.06; 95% CI: 1.01, 1.11). In the mediation analyses, the biomarkers explained 3.07-14.80% of the association between UPF intake and RA. CONCLUSION: Higher UPF consumption was associated with an increased risk of RA, which may be mediated by inflammation, lipids, and liver enzymes. Lower UPF consumption is recommended to reduce RA incidence.
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Importance: Previous studies on alcohol consumption and incident gout have mostly included men or combined both sexes, and the sex-specific associations between alcohol consumption and gout are poorly understood. Objective: To evaluate the consumption of total and specific alcoholic beverages in association with incident gout in men and women. Design, Setting, and Participants: This prospective cohort study included 401â¯128 participants in the UK Biobank aged 37 to 73 years who were free of gout at baseline (2006-2010). Participants were followed up through December 31, 2021, and data were analyzed between August 2023 and June 2024. Exposure: Questionnaire-based consumption of total alcohol and specific alcoholic beverages. Main Outcomes and Measures: The outcome was incident gout, identified using hospital records. Multivariable Cox proportional hazards regression models were used to estimate sex-specific hazard ratios (HRs) and 95% CIs of incident gout associated with alcohol consumption, with a particular consideration of reverse causation bias. Results: The main analysis included 179â¯828 men (mean [SD] age, 56.0 [8.2] years) and 221â¯300 women (mean [SD] age, 56.0 [8.0] years). Current drinkers showed a higher risk of gout than never drinkers among men (HR, 1.69; 95% CI, 1.30-2.18) but not among women (HR, 0.83; 95% CI, 0.67-1.03). Among current drinkers, higher total alcohol consumption was associated with a higher risk of gout among both sexes and more strongly among men than women (men: HR, 2.05 [95% CI, 1.84-2.30]; women: HR, 1.34 [95% CI, 1.12-1.61]). The most evident sex difference in the consumption of specific alcoholic beverages was observed for beer or cider (men: mean [SD], 4.2 [4.8] pints per week; women: mean [SD], 0.4 [1.1] pints per week). Consumption of champagne or white wine, beer or cider, and spirits each was associated with a higher risk of gout among both sexes, with beer or cider showing the strongest association per 1 pint per day (men: HR, 1.60 [95% CI, 1.53-1.67]; women: HR, 1.62 [95% CI, 1.02-2.57]). Some inverse associations between light to moderate consumption of specific alcoholic beverages and gout were eliminated after adjusting for other alcoholic beverages and excluding individuals who had reduced alcohol consumption for health reasons, self-reported poor health, or had cardiovascular disease, cancer, or kidney failure at baseline, or developed gout within the first 2 years of follow-up. Conclusions and Relevance: In this cohort study, higher consumption of several specific alcoholic beverages was associated with a higher risk of gout among both sexes. The sex-specific associations for total alcohol consumption may be associated with differences between men and women in the types of alcohol consumed.
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Consumo de Bebidas Alcohólicas , Bebidas Alcohólicas , Gota , Humanos , Gota/epidemiología , Gota/etiología , Masculino , Femenino , Persona de Mediana Edad , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/efectos adversos , Anciano , Estudios Prospectivos , Adulto , Bebidas Alcohólicas/estadística & datos numéricos , Bebidas Alcohólicas/efectos adversos , Factores de Riesgo , Reino Unido/epidemiología , Modelos de Riesgos Proporcionales , Incidencia , Factores SexualesRESUMEN
Although unregulated aliphatic disinfection byproducts (DBPs) had a much higher concentration and cytotoxicity than known aromatic DBPs, a recent study indicated that seven classes of regulated and unregulated priority DBPs (one and two-carbon-atom DBPs) just accounted for 16.2% of disinfected water cytotoxicity in the U.S., meaning some of the highly toxic aliphatic DBPs may be overlooked. Haloketones (HKs) are an essential class of priority DBPs with a 1-100 µg/L concentration in drinking water but lack cytotoxicity data. This study investigated the cytotoxicity of seven HKs using Chinese hamster ovary (CHO) cells. The order for cytotoxicity of HKs from most to least toxic was: 1,3-dichloroacetone (LC50: 1.0 ± 0.20 µM) ≈ 1,3-dibromoacetone (1.5 ± 0.19 µM) ≈ bromoacetone (1.9 ± 0.49 µM) > chloroacetone (4.3 ± 0.22 µM) > 1,1,3-trichloropropanone (6.6 ± 0.46 µM) > 1,1,1-trichloroacetone (222 ± 7.7 µM) > hexachloroacetone (3269 ± 344 µM). The cytotoxicity of HKs was higher than most regulated and priority aliphatic DBPs in mono-halogenated, di-halogenated, and tri-halogenated categories. A prediction model of HK cytotoxicity was developed based on the quantitative structure-activity relationship (QSAR), optimizing structures and computing descriptors with Gaussian 09 W. The average concentrations of HKs in representative drinking water samples from South Carolina (U.S.) and Suzhou (China) were 12.4 and 0.9 µg/L, respectively, accounting for 18.8% and 1.7% of their specific total DBPs measured (i.e. not TOX). For South Carolina drinking water, their contributions to total calculated additive cytotoxicity of aliphatic DBPs and overall drinking water cytotoxicity were 86.7% and 14.0%, respectively, demonstrating that HKs are an essential class of overlooked DBPs with a high contribution to drinking water cytotoxicity. Our study can help to explain the conflict that why regulated and priority DBPs (except HKs) just accounted for 16% of chlorinated drinking water cytotoxicity even enough they had much higher concentration and cytotoxicity than known aromatic DBPs.
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Cricetulus , Agua Potable , Contaminantes Químicos del Agua , Animales , Células CHO , Contaminantes Químicos del Agua/toxicidad , Desinfección , Purificación del Agua , Cricetinae , Cetonas/toxicidad , Desinfectantes/toxicidadRESUMEN
CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of â¼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.
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Amino acids (AAs) account for about 15-35% of dissolved organic nitrogen (DON), and are known as the important precursors of nitrogenous disinfection by-products (N-DBPs). Determining the formation potential (FP) of AAs to DBPs is used to reveal the key precursors of DBPs for further control, while the ideal method for N-DBPs FP of AAs during chlorination is not revealed. In this study, the ideal FP test models for five classes of priority DBPs during chlorination of four representative AAs (accounted for about 35% of total AAs) were analyzed. For haloaldehydes (HALs), haloketones (HKs), haloacetonitriles (HANs), haloacetamides (HAMs), and halonitromethanes (HNMs), their FPs during chlorination of four AAs were 0.1-13.0, 0.01-1.1, 0.1-104, not detectable (nd)-173, and nd-0.4 µg/mg, respectively. The FPs of priority DBPs had significant deviations between different FP test models and different tested AAs. For HALs, the model, whose chlorine dosage was determined by 15 × molar concentration of AAs [Cl (mM) = 15 × M](named: model II), was the ideal model. For HKs, model II was also the ideal FP test model for AAs with ≤3 carbons, while for AAs with 4 carbons, the model, whose chlorine dosage was determined by keeping the residual chlorine at 1 ± 0.2 mg/L after 24 h of reaction (named: model 4), was the ideal model. For HANs and HNMs, model 4 was the ideal FP test model for most of the studied AAs. The performance of HAMs during chlorination of amino acids was totally different from other P-DBPs, and model 3 was recommended to be the ideal model, in which chlorine dosage was determined by 3 × mass concentration of AAs [Cl (mg/L) = X × DOC]. This study is a reference that helps researchers select an ideal model for N-DBPs FP study of AAs.
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Aminoácidos , Cloro , Desinfectantes , Desinfección , Halogenación , Contaminantes Químicos del Agua , Aminoácidos/química , Aminoácidos/análisis , Cloro/química , Desinfectantes/química , Desinfectantes/análisis , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodosRESUMEN
Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.
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Eosina Amarillenta-(YS)/análogos & derivados , Interleucina-8 , Fosfatidiletanolaminas , Preeclampsia , Embarazo , Humanos , Femenino , Interleucina-8/genética , Fosfatidilinositol 3-Quinasas , Preeclampsia/genética , Placenta , Arterias , Medios de Cultivo Condicionados , Proteínas Adaptadoras Transductoras de Señales , Proteínas Reguladoras de la ApoptosisRESUMEN
Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.
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Oryza , Fitomejoramiento , Secuencias Reguladoras de Ácidos Nucleicos , Estrés Fisiológico/genética , Cationes/metabolismo , Variación GenéticaRESUMEN
Background: A healthy eating pattern characterized by a higher intake of healthy plant foods has been associated with a lower risk of premature mortality, but whether this applies to individuals with varying glycemic status remains unclear. Methods: This study included 4621 participants with diabetes and 8061 participants with prediabetes from the US National Health and Nutrition Examination Survey (2007-2016). Using the dietary data assessed by two 24 h dietary recalls, a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) were created based on 15 food groups and were assessed for their relationships with mortality risk. Results: Over a median follow-up of 7.2 years, there were 1021 deaths in diabetes and 896 deaths in prediabetes. A higher hPDI (highest vs. lowest quartile) was associated with a 41% (HR = 0.59, 95% CI: 0.49-0.72; P-trend < 0.001) lower risk of all-cause mortality in diabetes and a 31% (HR = 0.69, 95% CI: 0.55-0.85; P-trend < 0.001) lower risk in prediabetes. A higher uPDI was associated with an 88% (HR = 1.88, 95% CI: 1.55-2.28; P-trend < 0.001) higher risk of mortality in diabetes and a 63% (HR = 1.63, 95% CI: 1.33-1.99; P-trend < 0.001) higher risk in prediabetes. Mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.0% to 10.9% of the relationships between hPDI or uPDI and all-cause mortality among participants with diabetes. Conclusions: For adults with diabetes as well as those with prediabetes, adhering to a plant-based diet rich in healthier plant foods is associated with a lower mortality risk, whereas a diet that incorporates less healthy plant foods is associated with a higher mortality risk.
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Biomarcadores , Diabetes Mellitus , Dieta a Base de Plantas , Encuestas Nutricionales , Estado Prediabético , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Diabetes Mellitus/mortalidad , Estado Prediabético/mortalidad , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Rare gene variants have been found to play a role in complex disorders. Preeclampsia, and especially early-onset preeclampsia, has a strong genetic link. However, the role of rare variants in the offspring of mothers with preeclampsia remains unclear. In this study, whole-exome sequencing (WES) was used to identify rare pathogenic variants in two families with early-onset preeclampsia. Two heterozygous rare variants in CCDC7, c.625C>T (p.R209C) and c.1015C>T (p.R339X), were detected in two families and were cosegregated in the offspring of preeclamptic pregnancies. We examined the spatiotemporal expression pattern of CCDC7 in human placental villi and the effects of CCDC7 on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of CCDC7 in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The CCDC7 p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of CCDC7 suppressed the migration and invasion of JEG-3 cells. In conclusion, CCDC7 is a potential susceptibility gene for preeclampsia, which is key for the migration and invasion of trophoblast cells. Rare variants of preeclampsia in offspring may play a crucial role in the pathogenesis of preeclampsia and require further research.
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BACKGROUND: The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for placenta accreta spectrum could enable early treatment and improved outcomes. Endometrial thickness plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of endometrial thickness on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of endometrial thickness on placenta accreta spectrum. OBJECTIVE: This study aimed to evaluate the association between preimplantation endometrial thickness and the occurrence of placenta accreta spectrum in women undergoing assisted reproductive technology cycles. STUDY DESIGN: A total of 4637 women who had not undergone previous cesarean delivery and who conceived by in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 and December 2020 were included in this study. To explore the relationship between endometrial thickness and placenta accreta spectrum, we used smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between endometrial thickness and placenta accreta spectrum while adjusting for potential confounding factors. Propensity score matching was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we used causal mediation effect analysis to investigate the mediating role of endometrial thickness in the relationship between gravidity and ovarian stimulation protocol and the occurrence of placenta accreta spectrum. RESULTS: Among the 4637 women included in this study, pregnancies with placenta accreta spectrum (159; 3.4%) had significantly thinner endometrial thickness (non-placenta accreta spectrum, 10.08±2.04 mm vs placenta accreta spectrum, 8.88±2.21 mm; P<.001) during the last ultrasound before embryo transfer. By using smooth curve fitting, it was found that changes in endometrial thickness had a significant effect on the incidence of placenta accreta spectrum up to a thickness of 10.9 mm, beyond which the effect plateaued. Then, the endometrial thickness was divided into the following 4 groups: ≤7, >7 to ≤10.9, >10.9 to ≤13, and >13 mm. The absolute rates of placenta accreta spectrum in each group were 11.91%, 3.73%, 1.35%, and 2.54%, respectively. Compared with women with an endometrial thickness from 10.9 to 13 mm, the odds of placenta accreta spectrum increased from an adjusted odds ratio of 2.27 (95% confidence interval, 1.33-3.86) for endometrial thickness from 7 to 10.9 mm to an adjusted odds ratio of 7.15 (95% confidence interval, 3.73-13.71) for endometrial thickness <7 mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 11.80; 95% confidence interval, 7.65-18.19). Moreover, endometrial thickness <7 mm was still an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 3.91; 95% confidence interval, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on placenta accreta spectrum were mediated by endometrial thickness. CONCLUSION: The findings of our study indicate that thin endometrial thickness is an independent risk factor for placenta accreta spectrum in women without previous cesarean delivery undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than that of placenta previa. Furthermore, our results demonstrate that endometrial thickness plays a significant mediating role in the relationship between gravidity or ovarian stimulation protocol and placenta accreta spectrum.
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Hexafluoropropylene oxide dimer acid (GenX) is an alternative to perfluorooctanoic acid (PFOA), whose environmental concentration is close to its maximum allowable value established by the US Environmental Protection Agency, so its effects on human health are of great concern. The liver is one of the most crucial target organ for GenX, but whether GenX exposure induces liver cancer still unclear. In this research project, male C57 mice were disposed to GenX in drinking water at environmental concentrations (0.1 and 10 µg/L) and higher concentrations (1 and 100 mg/L) for 14 weeks to explore its effects on liver injury and potential carcinogenicity in mice. GenX was found to cause a dose-dependent increase in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG). As the content of GenX in drinking water increased, so did the concentrations of Glypican-3 (GPC-3) and detachment gamma-carboxyprothrombin (DCP), indicators of early hepatocellular cancer. GenX destroyed the boundaries and arrangements of hepatocytes, in which monocyte infiltration, balloon-like transformation, and obvious lipid vacuoles were observed between cells. Following exposure to GenX, Masson sections revealed a significant quantity of collagen deposition in the liver. Alpha-feto protein (AFP), vascular endothelial growth factor (VEGF), Ki67, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) gene expression increased in a dose-dependent manner in the treatment group relative to the control group. In general, drinking water GenX exposure induced liver function impairment, elevated blood lipid level, caused liver pathological structure damage and liver fibrosis lesions, changed the liver inflammatory microenvironment, and increased the concentration of liver-related tumor indicator even in the environmental concentration, suggesting GenX is a potential carcinogen.
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Carcinoma Hepatocelular , Agua Potable , Fluorocarburos , Neoplasias Hepáticas , Ratones , Masculino , Humanos , Animales , Carcinoma Hepatocelular/inducido químicamente , Metaloproteinasa 2 de la Matriz , Factor A de Crecimiento Endotelial Vascular , Neoplasias Hepáticas/inducido químicamente , Fluorocarburos/análisis , Hígado/química , Microambiente TumoralRESUMEN
OBJECTIVE: Compare the clinical severity of second preeclampsia with the first preeclampsia. METHODS: This retrospective longitudinal cohort study was conducted in three teaching hospitals in Guangzhou, where there were a total of 296â405 deliveries between 2010 and 2021. Two consecutive singleton deliveries complicated with preeclampsia were included. Clinical features, laboratory results within 1âweek before delivery, and maternal and neonatal outcomes of both deliveries were collected. Univariate analyses were made using paired Wilcoxon tests and McNemar tests. Multivariable logistic regression and generalized linear models were performed to assess the association of adverse maternal and neonatal outcomes with second preeclampsia. RESULTS: A total of 151 women were included in the study. The mean maternal age was 28 and 33âyears for the first and second deliveries, respectively. The proportion of preventive acetylsalicylic acid use was 4.6% for the first delivery and 15.2% for the second delivery. No significant differences were observed in terms of blood pressure on admission, gestational weeks of admission and delivery, application of perinatal antihypertensive agents, rates of preterm delivery, and severe features between the two occurrences. However, the rates of heart disease, edema, and admission to the ICU were lower, and hospital stays were shorter in the second preeclampsia compared with the first preeclampsia. Sensitivity analysis conducted among women who did not use preventive acetylsalicylic acid yielded similar results. After adjusting for potential confounding variables, the occurrence of second preeclampsia was associated with significantly decreased risks of heart disease, edema, complications, and admission to the NICU, with odds ratios ranging between 0.157 and 0.336. CONCLUSION: Contrary to expectations, the second preeclampsia did not exhibit worse manifestations or outcomes to the first occurrence. In fact, some clinical features and outcomes appeared to be better in the second preeclampsia.
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Cardiopatías , Preeclampsia , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Aspirina/uso terapéutico , Edema , Estudios Longitudinales , Preeclampsia/diagnóstico , Preeclampsia/epidemiología , Estudios RetrospectivosRESUMEN
OBJECTIVES: We aim to establish a predictive model for recurrent preeclampsia. METHODS: A retrospective review of medical records from three hospitals between 2010 and 2021 was conducted. The study included women who had two consecutive singleton deliveries at the same hospital, with the first delivery complicated by preeclampsia. A multivariable logistic regression model was constructed using a training cohort, and subsequently cross-validated and tested using an independent cohort. The model's performance was assessed in terms of discrimination and calibration, and its clinical utility was evaluated using decision curve analysis (DCA). RESULTS: Among 296â405 deliveries, 694 women met the inclusion criteria, with 151 (21.8%) experiencing recurrent preeclampsia. The predictive model incorporated 10 risk factors from previous preeclampsia, including gestational weeks with elevated blood pressure, gestational diabetes mellitus (GDM), pericardial effusion, heart failure, limb edema, serum creatinine, white blood cell count, low platelet counts within one week before delivery, SBP on the first postpartum day, and postpartum antihypertensive use. Additionally, one risk factor from the index pregnancy was included, which was antihypertensive use before 20âweeks. The model demonstrated better discrimination, calibration, and a net benefit across a wide range of recurrent preeclampsia risk thresholds. Furthermore, the model has been translated into a clinical risk calculator, enabling clinicians to calculate individualized risks of recurrent preeclampsia. CONCLUSION: Our study demonstrates that a predictive tool utilizing routine clinical and laboratory factors can accurately estimate the risk of recurrent preeclampsia. This predictive model has the potential to facilitate shared decision-making by providing personalized and risk-stratified care.
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Diabetes Gestacional , Hipertensión , Preeclampsia , Embarazo , Femenino , Humanos , Preeclampsia/diagnóstico , Preeclampsia/epidemiología , Preeclampsia/etiología , Antihipertensivos , Hipertensión/complicaciones , Factores de RiesgoRESUMEN
Hydrogels with three-dimensional structures have been widely applied in various applications because of their tunable structures, which can be easily tailored with desired functionalities. However, the application of hydrogel materials in bioengineering is still constrained by their limited dosage flexibility and the requirement of invasive surgical procedures. Compared to traditional hydrogels, injectable hydrogels, with shear-thinning and/or in situ formation properties, simplify the implantation process and reduce tissue invasion, which can be directly delivered to target sites using a syringe injection, offering distinct advantages over traditional hydrogels. These injectable hydrogels incorporate physically non-covalent and/or dynamic covalent bonds, granting them self-healing abilities to recover their structural integrity after injection. This review summarizes our recent progress in preparing injectable hydrogels and discusses their performance in various bioengineering applications. Moreover, the underlying molecular interaction mechanisms that govern the injectable and functional properties of hydrogels were characterized by using nanomechanical techniques such as surface forces apparatus (SFA) and atomic force microscopy (AFM). The remaining challenges and future perspectives on the design and application of injectable hydrogels are also discussed. This work provides useful insights and guides future research directions in the field of injectable hydrogels for bioengineering.
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Hidrogeles , Hidrogeles/química , InyeccionesRESUMEN
OBJECTIVE: This study aims to develop physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) predictive models for nifedipine in pregnant women, enhancing precision medicine and reducing adverse reactions for both mothers and infants. METHODS: A PBPK/PD model was constructed using PK-Sim, MoBi, and MATLAB software, integrating literature and pregnancy-specific physiological information. The process involved: (1) establishing and validating a PBPK model for serum clearance after intravenous administration in non-pregnant individuals, (2) establishing and validating a PBPK model for serum clearance after oral administration in non-pregnant individuals, (3) constructing and validating a PBPK model for enzyme clearance after oral administration in non-pregnant individuals, and (4) adjusting the PBPK model structure and enzyme parameters according to pregnant women and validating it in oral administration. (5) PK/PD model was explored through MATLAB, and the PBPK and PK/PD models were integrated to form the PBPK/PD model. RESULTS: The Nifedipine PBPK model's predictive accuracy was confirmed by non-pregnant and pregnant validation studies. The developed PBPK/PD model accurately predicted maximum antihypertensive effects for clinical doses of 5, 10, and 20 mg. The model suggested peak effect at 0.86 h post-administration, achieving blood pressure reductions of 5.4 mmHg, 14.3 mmHg, and 21.3 mmHg, respectively. This model provides guidance for tailored dosing in pregnancy-induced hypertension based on targeted blood pressure reduction. CONCLUSION: Based on available literature data, the PBPK/PD model of Nifedipine in pregnancy demonstrated good predictive performance. It will help optimize individualized dosing of Nifedipine, improve treatment outcomes, and minimize the risk of adverse reactions in mothers and infants.
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Nifedipino , Mujeres Embarazadas , Lactante , Humanos , Femenino , Embarazo , Medicina de Precisión , Modelos Biológicos , Toma de Decisiones ClínicasRESUMEN
BACKGROUND: Wide phthalate exposure has been associated with both declines in renal function and an elevated risk of mortality. Whether phthalate-associated risk of premature mortality differs by renal function status remains unclear. METHODS: This study included 9605 adults from the U.S. National Health and Nutrition Examination Survey. Urinary concentrations of 11 phthalate metabolites were assessed using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. According to estimated glomerular filtration rate (eGFR), participants were grouped as having normal or modestly declined renal functions, or chronic kidney disease (CKD). Multivariable Cox regression models estimated all-cause mortality associated with phthalate exposure, overall and by renal function status. RESULTS: Overall, Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and Mono-(2-ethyl-5-carbox-ypentyl) phthalate (MECPP) were associated with an elevated risk of mortality (P-trend across tertile <0.05). Moreover, significant interactions were observed between eGFR and MEHHP, MEOHP, MECPP, DEHP in the whole population (P for interactions <0.05). After stratification by renal function, total Di (2-ethylhexyl) phthalate (DEHP) was additionally found to be associated with mortality risk in the CKD group (HR = 1.12; 95% CI: 1.01, 1.25). Co-exposure to the 11 phthalate metabolites was associated with a higher risk of all-cause mortality in the CKD (HR = 1.47; 95% CI: 1.18, 1.84) and modestly declined renal function group (HR = 1.25; 95% CI: 1.09, 1.44). CONCLUSIONS: The associations between phthalate exposure and risk of all-cause mortality were primarily observed in CKD patients, reinforcing the need for monitoring phthalate exposure in this patient population.
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Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Insuficiencia Renal Crónica , Adulto , Humanos , Exposición a Riesgos Ambientales/análisis , Encuestas Nutricionales , Ácidos Ftálicos/metabolismo , Insuficiencia Renal Crónica/inducido químicamente , Riñón/metabolismo , Contaminantes Ambientales/análisisRESUMEN
Soil is the source and sink of microplastics (MPs), which is more polluted than water and air. In this paper, the pollution levels of MPs in the agriculture, roadside, urban and landfill soils were reviewed, and the influence of MPs on soil ecosystem, including soil properties, microorganisms, animals and plants, was discussed. According to the results of in vivo and in vitro experiments, the possible risks of MPs to soil ecosystem and human health were predicted. Finally, in light of the current status of MPs research, several prospects are provided for future research directions to better evaluate the ecological risk and human health risk of MPs. MPs concentrations in global agricultural soils, roadside soils, urban soils and landfill soils had a great variance in different studies and locations. The participation of MPs has an impact on all aspects of terrestrial ecosystems. For soil properties, pH value, bulk density, pore space and evapotranspiration can be changed by MPs. For microorganisms, MPs can alter the diversity and abundance of microbiome, and different MPs have different effects on bacteria and fungi differently. For plants, MPs may interfere with their biochemical and physiological conditions and produce a wide range of toxic effects, such as inhibiting plant growth, delaying or reducing seed germination, reducing biological and fruit yield, and interfering with photosynthesis. For soil animals, MPs can affect their mobility, growth rate and reproductive capacity. At present epidemiological evidences regarding MPs exposure and negative human health effects are unavailable, but in vitro and in vivo data suggest that they pose various threats to human health, including respiratory system, digestive system, urinary system, endocrine system, nervous system, and circulation system. In conclusion, the existence and danger of MPs cannot be ignored and requires a global effort.
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Microbiota , Suelo , Animales , Humanos , Ecosistema , Microplásticos , Plásticos , AgriculturaRESUMEN
Hexafluoropropylene oxide dimer acid (HFPO-DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 µg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 µM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1ß, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Agua Potable , Fluorocarburos , Propionatos , Ratones , Masculino , Humanos , Animales , Metabolismo de los Lípidos , PPAR alfa/farmacología , Agua Potable/análisis , Fluorocarburos/farmacología , Hígado , Transducción de SeñalRESUMEN
Cation-π interaction is one of the most important noncovalent interactions identified in biosystems, which has been proven to play an essential role in the strong adhesion of marine mussels. In addition to the well-known catecholic amino acid, l-3,4-dihydroxyphenylalanine, mussel foot proteins are rich in various aromatic moieties (e.g., tyrosine, phenylalanine, and tryptophan) and cationic residues (e.g., lysine, arginine, and histidine), which favor a series of short-range cation-π interactions with adjustable strengths, serving as a prototype for the development of high-performance underwater adhesives. This work highlights our recent advances in understanding and utilizing cation-π interactions in underwater adhesives, focusing on three aspects: (1) the investigation of the cation-π interaction mechanisms in mussel foot proteins via force-measuring techniques; (2) the modulation of cation-π interactions in mussel mimetic polymers with the variation of cations, anions, and aromatic groups; (3) the design of wet adhesives based on these revealed principles, leading to functional materials in the form of films, coacervates, and hydrogels with biomedical and engineering applications. This review provides valuable insights into the development and optimization of smart materials based on cation-π interactions.