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OBJECTIVE: To develop and evaluate the predictive value of a simplified lung ultrasound (LUS) method for forecasting respiratory support in term infants. METHODS: This observational, prospective, diagnostic accuracy study was conducted in a tertiary academic hospital between June and December 2023. A total of 361 neonates underwent LUS examination within 1 h of birth. The proportion of each LUS sign was utilized to predict their respiratory outcomes and compared with the LUS score model. After identifying the best predictive LUS sign, simplified models were created based on different scan regions. The optimal simplified model was selected by comparing its accuracy with both the full model and the LUS score model. RESULTS: After three days of follow-up, 91 infants required respiratory support, while 270 remained healthy. The proportion of confluent B-lines demonstrated high predictive accuracy for respiratory support, with an area under the curve (AUC) of 89.1% (95% confidence interval [CI]: 84.5-93.7%). The optimal simplified model involved scanning the R/L 1-4 region, yielding an AUC of 87.5% (95% CI: 82.6-92.3%). Both the full model and the optimal simplified model exhibited higher predictive accuracy compared to the LUS score model. The optimal cut-off value for the simplified model was determined to be 15.9%, with a sensitivity of 76.9% and specificity of 91.9%. CONCLUSIONS: The proportion of confluent B-lines in LUS can effectively predict the need for respiratory support in term infants shortly after birth and offers greater reliability than the LUS score model.
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Pulmón , Valor Predictivo de las Pruebas , Ultrasonografía , Humanos , Recién Nacido , Femenino , Estudios Prospectivos , Masculino , Pulmón/diagnóstico por imagen , Ultrasonografía/métodos , Respiración Artificial/métodos , Nacimiento a Término/fisiología , Estudios de SeguimientoRESUMEN
This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens â and â ¢, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens â and â ¢, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.
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Ferroptosis , Insuficiencia Cardíaca , Ratas , Animales , Ratas Sprague-Dawley , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Volumen Sistólico , Especies Reactivas de Oxígeno , Función Ventricular Izquierda , Ratas Wistar , Insuficiencia Cardíaca/tratamiento farmacológico , Fibrosis , Colágeno/farmacologíaRESUMEN
Autonomic nervous system imbalance is intricately associated with the severity and prognosis of pulmonary arterial hypertension (PAH). Carotid baroreceptor stimulation (CBS) is a nonpharmaceutical intervention for autonomic neuromodulation. The effects of CBS on monocrotaline-induced PAH were investigated in this study, and its underlying mechanisms were elucidated. The results indicated that CBS improved pulmonary hemodynamic status and alleviated right ventricular dysfunction, improving pulmonary arterial remodeling and right ventricular remodeling, thus enhancing the survival rate of monocrotaline-induced PAH rats. The beneficial effects of CBS treatment on PAH might be mediated through the inhibition of sympathetic overactivation and inflammatory immune signaling pathways.
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This study involved the design and synthesis of a series of novel 4-chromanone-derived compounds. Their in vivo anti-cucumber mosaic virus (CMV) activity in field trials against CMV disease in Passiflora spp. was then assessed. Bioassay results demonstrated that compounds 7c and 7g exhibited remarkable curative effects and protection against CMV, with inhibition rates of 57.69% and 51.73% and 56.13% and 52.39%, respectively, surpassing those of dufulin and comparable to ningnanmycin. Field trials results indicated that compound 7c displayed significant efficacy against CMV disease in Passiflora spp. (passion fruit) after the third spraying at a concentration of 200 mg/L, with a relative control efficiency of 47.49%, surpassing that of dufulin and comparable to ningnanmycin. Meanwhile, nutritional quality test results revealed that compound 7c effectively enhanced the disease resistance of Passiflora spp., as evidenced by significant increases in soluble protein, soluble sugar, total phenol, and chlorophyll contents in Passiflora spp. leaves as well as improved the flavor and taste of Passiflora spp. fruits, as demonstrated by notable increases in soluble protein, soluble sugar, soluble solid, and vitamin C contents in Passiflora spp. fruits. Additionally, a transcriptome analysis revealed that compound 7c primarily targeted the abscisic acid (ABA) signaling pathway, a crucial plant hormone signal transduction pathway, thereby augmenting resistance against CMV disease in Passiflora spp. Therefore, this study demonstrates the potential application of these novel 4-chromanone-derived compounds as effective inducers of plant immunity for controlling CMV disease in Passiflora spp. in the coming decades.
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Cromonas , Cucumovirus , Infecciones por Citomegalovirus , Passiflora , Frutas , Resistencia a la Enfermedad , Azúcares/metabolismoRESUMEN
Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies. Activation of the ADORA2A signaling rewires the proline metabolism via an ERK/MYC/PYCR cascade. Increased proline synthesis promotes deacetylases SIRT6/7-mediated deacetylation of histone H3 at lysine 27 (H3K27), and thereby biases a global transcriptional output toward a neuroendocrine lineage profile. Ablation of Adora2a in genetically engineered mouse models inhibits the development and progression of neuroendocrine prostate and lung cancers, and, intriguingly, prevents the adenocarcinoma-to-neuroendocrine phenotypic transition. Importantly, pharmacological blockade of ADORA2A profoundly represses neuroendocrine prostate and lung cancer growth in vivo. Therefore, we believe that ADORA2A can be used as a promising therapeutic target to govern the epigenetic reprogramming in neuroendocrine malignancies.
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Neoplasias Pulmonares , Neoplasias de la Próstata , Sirtuinas , Animales , Humanos , Masculino , Ratones , Línea Celular Tumoral , Epigénesis Genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Prolina/metabolismo , Prolina/uso terapéutico , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/patología , Sirtuinas/metabolismoRESUMEN
Macropodus opercularis is an ornamental fish species endemic to China, with obvious sexual dimorphism in phenotype. To obtain the gene expression profile of the gonads of M. opercularis and explore its sex-related genes, six cDNA libraries were constructed from the sexually mature M. opercularis, and RNA-seq analysis was performed. The sequenced clean data were assembled by de novo splicing to generate 171,415 unigenes, and differentially expressed genes (DEGs) screening revealed that there were 41,638 DEGs in the gonads of M. opercularis. By comparing those DEGS in the ovary with the testis, we found 29,870 DEGs were upregulated and 11,768 DEGs were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis showed that GO terms related to cell cycle and gamete formation were enriched, and pathway signals related to sex differences, such as FoxO signalling pathway and PI3K-Akt signalling pathway, were also detected. Reverse transcript fluorescence quantitative PCR (RT-qPCR) validation of 14 DEGs associated with sex differences showed that the RT-qPCR results were consistent with RNA-Seq analysis, and five genes, foxl2, sox3, foxo, zar1, cyp19a1, were significantly expressed in the ovaries. dmrt1, cyp11b, amh, sf1, sox9, gdf6, dmrt3, fstl1 and hsd11b2, a total of nine genes were significantly expressed in the testis. The results of this study provide a basis for the study of gonadal differentiation, developmental mechanisms and related functional genes in M. opercularis.
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Gónadas , Fosfatidilinositol 3-Quinasas , Femenino , Animales , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Gónadas/metabolismo , Perfilación de la Expresión Génica , Ovario/metabolismo , Testículo/metabolismo , Transcriptoma , Peces/metabolismoRESUMEN
OBJECTIVE: To investigate the therapeutic effect of Buyang huanwu decoction (BYHWD) on sepsis-induced myocardial injury (SIMI) and explore the mechanism by which BYHWD mitigates SIMI. METHODS: The Lipopolysaccharide (LPS)-induced SIMI mouse model was established to detect the effect of BYHWD-low (1 mg/kg), BYHWD-middle (5 mg/kg), and BYWHD-high (20 mg/kg) on SIMI. The survival of these BYHWD-treated septic mice was investigated. The histology of myocardial tissues was determined by hematoxylin and eosin (H&E) staining. The apoptotic index and inflamed microenvironment of myocardial tissues were assessed by immunofluorescent staining (IF) and flow cytometry analysis. Liquid chromatography-mass spectrometry (LC-MS/MS) was employed to determine the key chemical components in the serum of BYHWD-loaded septic mice. Immunoblotting assay was utilized to detect NF-κB and TGF-ß signaling activity, and M1/M2-macrophage markers using RAW264.7 cells. RESULTS: The high dosage of BYHWD (BYHWD-high, 20 mg/Kg) significantly attenuated SIMI and improved the survival of septic mice. The BYHWD-high solution markedly reduced myocardial cell apoptosis and mitigated the inflamed microenvironment by suppressing CD45+ immune cell infiltration. Importantly, BYHWD decreased macrophage accumulation and promoted an M2-macrophage polarization. Paeoniflorin (PF) and calycosin-7-O-ß-glucoside (CBG) were identified as the key molecules in BYWHD with therapeutic effect. PF (10 µM) and CBG (1 µM) inhibited NF-κB signaling, meanwhile they upregulated the TGF-ß pathway, thereby facilitating an M2-macrophage phenotypic transition in RAW264.7 cells. CONCLUSIONS: BYHWD, with two effective components PF and CBG, can mitigate SIMI by suppressing the inflamed myocardial microenvironment and skewing an immunosuppressive M2-macrophage phenotype.
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Salidroside (SAL) is a natural bioactive compound with anti-oxidative, anti-inflammatory, and neuroprotective properties. In the present study, we generate an experimental design to investigate SAL-mediated protective effect and underlying mechanism on lipopolysaccharide (LPS)-induced neuroinflammation and cognitive impairment in the septic encephalopathy mice model (SEMM). In SEMM, Open-Field Test (OFT) and Novel Object Recognition Test evaluated LPS-induced cognitive impairment, behavioural phenotypes, and memory impairment (NOR). Cytokines and protein expression were assessed using ELISA assay, RT-qPCR, and Western blotting. Our results showed cognitive dysfunction could be reversed when treated with SAL in SEMM. SAL treatment significantly reduced apoptotic TUNEL-positive cells and related gene expression (BAX and BCL-2) and considerably improved neuronal damage in SEMM. In addition, it markedly reduced the production of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and Iba-1-positive cells responsible for microglial activation in mice hippocampus (P < 0.05). The effects of SAL on ROS and oxidative stress markedly reduced malondialdehyde (MDA) content and increased superoxide dismutase (SOD) and catalase (CAT) in the hippocampal tissues of mice. Besides, SAL treatment enhanced LPS-induced autophagy in mice's hippocampus and increased autophagy-related protein expression (Beclin-1 and P62). In addition, the NLRP3 inflammasome pathway and its related proteins (NLRP3, ASC, and cleaved caspase-1) were suppressed by SAL treatment. However, SAL activated the SIRT1/Nrf2 pathway and exerts protection by enhanced expression of the proteins (SIRT1 and Nrf2) and downstream genes (HO-1 and NQO1). Our finding demonstrated that SAL employed neuroprotective effects in SEMM by promoting autophagy via activation of the SIRT1 pathway.
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Encefalopatías , Disfunción Cognitiva , Ratones , Animales , Lipopolisacáridos/efectos adversos , Sirtuina 1/metabolismo , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR , Factor 2 Relacionado con NF-E2 , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/inducido químicamente , Citocinas , Antiinflamatorios/uso terapéuticoRESUMEN
Intangible cultural heritage has a unique value. It is very important to evaluate and discover the value of intangible cultural heritage. Therefore, referring to the relevant references of countries around the world, this paper compares the research status of countries around the world with the development trend of China's intangible cultural heritage, indicating that the network resources of intangible cultural heritage can be converted into cultural capital according to the basic theory of cultural capital and then get an economic value. The use value of intangible cultural heritage is analyzed and considered according to IPA entity model analysis, kernel density estimation (KDE), and gray correlation calculation (calculated by using IPA analysis conclusion). Among them, because intangible cultural heritage cannot be measured and verified immediately, indirect measurement verification is carried out by selecting indirect indicators such as the total number of intangible cultural heritage and the development trend of intangible cultural heritage tourism. Based on the gray correlation analysis of the total number and relative density of national intangible cultural heritage and the intangible cultural heritage tourism and related industrial chains, the following proposals for the development trend of intangible cultural heritage are clearly put forward as follows: (1) Further excavate the meaning of "non-material property tourism" and increase the scope of development and design of cultural and art tourism network resources. (2) Make full use of the guiding effect of government departments on "intangible cultural heritage tourism," and improve the normalization of the combination of culture, art, and tourism. (3) Expand the whole industrial chain of "intangible cultural heritage tourism" in an orderly manner, and promote the concept of coordinated and sustainable development of cultural and art tourism.
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Reproducción , RetroalimentaciónRESUMEN
[This corrects the article DOI: 10.3389/fcimb.2021.820535.].
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In this study, using the botanical active component thiochromanone as the lead compound, a total of 32 new thiochromanone derivatives containing a carboxamide moiety were designed and synthesized and their in vitro antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicolaby (Xoc), and Xanthomonas axonopodis pv. citri (Xac) were determined, as well as their in vitro antifungal activities against Botryosphaeria dothidea (B. dothidea), Phomopsis sp., and Botrytis cinerea (B. cinerea). Bioassay results demonstrated that some of the target compounds exhibited moderate to good in vitro antibacterial and antifungal activities. In particular, compound 4e revealed excellent in vitro antibacterial activity against Xoo, Xoc, and Xac, and its EC50 values of 15, 19, and 23 µg/mL, respectively, were superior to those of Bismerthiazol and Thiodiazole copper. Meanwhile, compound 3b revealed moderate in vitro antifungal activity against B. dothidea at 50 µg/mL, and the inhibition rate reached 88%, which was even better than that of Pyrimethanil, however, lower than that of Carbendazim. To the best of our knowledge, this is the first report on the antibacterial and antifungal activities of this series of novel thiochromanone derivatives containing a carboxamide moiety.
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Botrytis/crecimiento & desarrollo , Cromanos , Phomopsis/crecimiento & desarrollo , Xanthomonas axonopodis/crecimiento & desarrollo , Xanthomonas/crecimiento & desarrollo , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Cromanos/síntesis química , Cromanos/química , Cromanos/farmacología , Relación Estructura-ActividadRESUMEN
The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue's robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.
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Péptidos/química , Péptidos/genética , Proteínas/química , Proteínas/genética , Adhesivos/química , Adulto , Animales , Cianoacrilatos/química , Modelos Animales de Enfermedad , Femenino , Regeneración Tisular Dirigida/métodos , Hemostasis , Humanos , Hígado/patología , Ratones , Ratas , Ratas Wistar , Piel/patología , Porcinos , Adhesivos Tisulares/química , Cicatrización de HeridasRESUMEN
A series of novel thiochromanone derivatives containing a sulfonyl hydrazone moiety were designed and synthesized. Their structures were determined by 1H-NMR, 13C-NMR, and HRMS. Bioassay results showed that most of the target compounds revealed moderate to good antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicolaby, and Xanthomonas axonopodis pv. citri. Compound 4i had the best inhibitory activity against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicolaby, and Xanthomonas axonopodis pv. citri, with the EC50 values of 8.67, 12.65, and 10.62 µg/mL, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, bioassay results showed that all of the target compounds proved to have lower antifungal activities against Sclerotinia sclerotiorum, Fusarium oxysporum, Gibberella zeae, Rhizoctonia solani, Verticillium dahlia, and Botrytis cinerea than those of Carbendazim.
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Cromanos/síntesis química , Cromanos/farmacología , Hidrazonas/síntesis química , Hidrazonas/farmacología , Sulfonas/síntesis química , Sulfonas/farmacología , Antibacterianos/farmacología , Antifúngicos/farmacología , Cromanos/química , Hongos/efectos de los fármacos , Hidrazonas/química , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Xanthomonas/efectos de los fármacosRESUMEN
Adhesive hydrogels have been developed for wound healing applications. However, their adhesive performance is impaired dramatically due to their high swelling on wet tissues. To tackle this challenge, we fabricated a new type of non-swelling protein adhesive for underwater and inâ vivo applications. In this soft material, the electrostatic complexation between supercharged polypeptides with oppositely charged surfactants containing 3,4-dihydroxylphenylalanine or azobenzene moieties plays an important role for the formation of ultra-strong adhesive coacervates. Remarkably, the adhesion capability is superior to commercial cyanoacrylate when tested in ambient conditions. Moreover, the adhesion is stronger than other reported protein-based adhesives in underwater environment. The ex vivo and in vivo experiments demonstrate the persistent adhesive performance and outstanding behaviors for wound sealing and healing.
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Materiales Biocompatibles/química , Ingeniería Genética , Hidrogeles/química , Péptidos/química , Péptidos/genética , Adhesivos Tisulares/química , Humanos , Tensoactivos/química , Cicatrización de HeridasRESUMEN
Complex coacervation enables important wet adhesion processes in natural and artificial systems. However, existed synthetic coacervate adhesives show limited wet adhesion properties, non-thermoresponsiveness, and inferior biodegradability, greatly hampering their translations. Herein, by harnessing supramolecular assembly and rational protein design, we present a temperature-sensitive wet bioadhesive fabricated through recombinant protein and surfactant. Mechanical performance of the bioglue system is actively tunable with thermal triggers. In cold condition, adhesion strength of the bioadhesive was only about 50â kPa. By increasing temperature, the strength presented up to 600â kPa, which is remarkably stronger than other biological counterparts. This is probably due to the thermally triggered phase transition of the engineered protein and the formation of coacervate, thus leading to the enhanced wet adhesion bonding.
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Adhesivos/química , Proteínas Recombinantes/química , Tensoactivos/química , Sustancias Viscoelásticas/química , Adhesividad , Transición de Fase , TemperaturaRESUMEN
BACKGROUND: Periodontitis is considered a risk factor for atherosclerosis, but the mechanism is not clear. It was reported that oral administration of Porphyromonas gingivalis altered the gut microbiota in mice. Gut dysbiosis and the intestinal metabolite trimethylamine N-oxide (TMAO) were verified to be associated with atherosclerosis. Therefore, the possible TMAO-related mechanism between periodontitis and atherosclerosis needs to be explored. METHODS: Experimental periodontitis was established by oral administration of P. gingivalis for 2 months in ApoE-/- mice. Mouse hemi-mandibles were scanned using Micro-CT. Quantification of TMAO was performed using liquid chromatography-tandem mass spectrometry. Mouse feces were collected and the bacterial DNA was extracted, then the gut microbiota was analyzed using 16S rRNA genes. Atherosclerotic lesion areas were quantified. Livers, small intestines, and large intestines were analyzed for gene expression. RESULTS: Aggravated atherosclerosis plaques were found in experimental periodontitis mice. Plasma TMAO, a pathogenic factor of atherosclerosis, was initially found to be increased in periodontitis mice. Changes in the composition and abundance of the intestinal microflora of periodontitis mice were found. Flavin monooxygenase 3 (FMO3), the catalyzing enzyme of TMAO in the liver, was significantly increased, accompanied by an increase of IL-6 in liver, the abnormal intestinal integrity and enhanced plasma LPS. The IL-6 and LPS were verified to be able to increase FMO3 in HepG2 cells. CONCLUSION: Our research discovered that experimental periodontitis in ApoE-/- mice induced gut dysbiosis and an increase in TMAO. These results suggest a possible mechanism by which periodontitis may accelerate atherosclerosis by influencing the intestinal microbes and the metabolism, which were triggered by inflammation of the liver and intestine.
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Aterosclerosis , Periodontitis , Animales , Aterosclerosis/microbiología , Metilaminas , Ratones , ARN Ribosómico 16S/genéticaRESUMEN
OBJECTIVE: To study the association between maternal age and adverse pregnancy outcome in twin pregnancy. METHODS: The clinical data of 2â363 women with twin pregnancy from January 2006 to June 2016 were retrospectively reviewed. According to the age, the women were divided into six groups: <20 years (n=15), 20-24 years (n=158), 25-29 years (n=894), 30-34 years (n=936), 35-39 years (n=320), and ≥40 years group (n=40). The above groups were compared in terms of related baseline features and incidence rates of adverse pregnancy outcomes (preterm birth, birth defect, stillbirth in late pregnancy and small-for-gestational-age birth). A generalized estimating equation was used to investigate the risk of adverse pregnancy outcomes in different age groups. RESULTS: After control for the factors including place of residence, primipara, pregnancy pattern, and gestational diseases, the incidence rates of very preterm birth and moderately preterm birth in the ≥40 years group were 2.60 and 1.99 times than those in the 25-29 years group respectively (P<0.05). The incidence rates of very preterm birth and late preterm birth in the 20-24 years group were 1.99 and 1.33 times than those in the 25-29 years group respectively (P<0.05). The incidence rates of stillbirth in late pregnancy in the <20 years group, the 20-24 years group, and the ≥40 years group were 9.10, 2.88 and 3.97 times than those in the 25-29 years group respectively (P<0.05). The incidence rates of small-for-gestational-age birth in the <20 years group and the 35-39 years group were 2.70 and 0.73 times than those in the 25-29 years group respectively (P<0.05). CONCLUSIONS: In twin pregnancy, pregnant women, aged <20 years, have a higher risk of smaller-for-gestational-age birth and stillbirth in late pregnancy, those aged ≥40 years have a higher risk of very preterm birth, moderately preterm birth and stillbirth in late pregnancy, and those aged 20-24 years have a higher risk of very preterm birth, late preterm birth and stillbirth in late pregnancy.
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Embarazo Gemelar , Nacimiento Prematuro , Adulto , Femenino , Humanos , Recién Nacido , Edad Materna , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Mortinato , Adulto JovenRESUMEN
AIMS: Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown. METHODS: We measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild-type control mice using liquid chromatography-mass spectrometry (LC-MS)-based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis. RESULTS: Metabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild-type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice. CONCLUSIONS: The data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU.