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BACKGROUND: In 2016, the "universal two-child" policy, allowing each couple to have two children, was introduced in China. The characteristic change of the long-term period after the implementation of the universal two-child policy was unclear. We studied trends in the obstetric characteristics and their potential impact on the rates of cesarean section and preterm birth in the era of China's universal two-child policy. METHODS: A tertiary center-based study (2010-2021) retrospectively focused single high-risk pregnancies who delivered from the one-child policy period (OCP, 2010-2015) to the universal two-child policy period (TCP, 2016-2021). A total of 39, 016 pregnancies were enrolled. Maternal demographics, complications, delivery mode and obstetric outcomes were analyzed. Furthermore, logistic regression analysis was used to explore the association between the cesarean section rate, preterm birth and implementation of the universal two-child policy, adjusting maternal age, parity, and fetal distress. RESULTS: Ultimately a total of 39,016 pregnant women met the criteria and were included in this analysis. The proportion of women with advanced maternal age (AMA) increased from 14.6% in the OCP to 31.6% in the TCP. The number of multiparous women increased 2-fold in the TCP. In addition, the overall rate of cesarean section significantly decreased over the policy change, regardless of maternal age, whereas the risk of preterm birth significantly increased in the TCP. Adjusting for maternal age, parity and fetal distress, the universal two-child policy showed a significantly favorable impact on the cesarean section rate (RR 0.745, 95%CI (0.714-0.777), P < 0.001). Compared to the OCP group, a higher increase in fetal distress and premature rupture of membranes (PROM) were observed in the TCP group. In pregnancies with AMA, there was no increase in the risk of postpartum hemorrhage, whereas more women who younger than 35 years old suffered from postpartum hemorrhage in TCP. The logistic regression model showed that the universal two-child policy was positively associated with the risk of postpartum hemorrhage (RR: 1.135, 95%CI: 1.025-1.257, P = 0.015). CONCLUSIONS: After the implementation of the universal two-child policy in China, the rate of the cesarean section significantly decreased, especially for women under 35 years old. However, the overall risk of postpartum hemorrhage increased in women under 35 years old, while there was no change in women with AMA. Under the new population policy, the prevention of postpartum hemorrhage in the young women should not be neglected.
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Política de Planejamento Familiar , Hemorragia Pós-Parto , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Adulto , Cesárea , Estudos Retrospectivos , Gestantes , Nascimento Prematuro/epidemiologia , Sofrimento Fetal , Paridade , China/epidemiologiaRESUMO
Low-dose prophylactic aspirin is widely recommended for pregnant women for the prevention of preeclampsia (PE). Although the efficacy of aspirin in preventing PE has been evaluated in many studies, due to the differences in dosage, initiation time, and screening methods for the identification of women at high risk of PE and the lack of a uniform opinion on the medication regimen of aspirin, currently in China there is no consensus on the standardized treatment scheme of aspirin for the prevention of PE in clinical guidelines. Herein, we reviewed the current available evidence and the recommendations of clinical guidelines concerning the controversies about aspirin dosage as well as the timing of starting and stopping aspirin, so as to provide further guidance for clinical practice. Based on the existing research findings on and clinical practice of using aspirin for PE prevention, we suggested that PE risk screening should be conducted at 11-13+6 weeks of gestation. In addition, the recommended dose for prophylactic use of aspirin for pregnant women at high risk of PE is 150 mg/d, and the recommended minimum effective dose is 100 mg/d. Pregnant women at high risk of PE should start taking low-dose aspirin orally before 16 weeks of pregnancy. Week 36 of gestation is considered the window of opportunity for discontinuation of low-dose aspirin.
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Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/diagnóstico , Aspirina/uso terapêutico , ChinaRESUMO
BACKGROUND: First-trimester cervical length for the prediction of spontaneous preterm delivery remains controversial. A better method for the measurement of the first-trimester cervical length and additional cervical ultrasound parameters for the identification of women at high risk for spontaneous preterm delivery are needed. OBJECTIVE: This study aimed to compare the predictive value of cervical length measured by 2 different methods in the first trimester of pregnancy to predict spontaneous preterm delivery and to explore the potential value of first-trimester cervical shear-wave elastography for the prediction of spontaneous preterm delivery. STUDY DESIGN: This was a prospective study in unselected singleton pregnancies at 11+0 to 13+6 weeks' gestation. Cervical length was measured by the following 2 methods in the base-cohort population: (1) a linear distance between the 2 ends of the glandular area around the endocervical canal (single-line method: cervical length-s) and (2) a sum of the linear distance from the internal os to the greatest cervical curvature and the linear distance from this point to the external os (2-line method: cervical length-t). In a substudy, cervical shear-wave elastography scores for 9 regions of interest (inner, middle, and external parts of anterior lip, endocervical canal, and posterior lip) in midsagittal plane were also obtained by transvaginal ultrasonography. The screening performance of the first-trimester cervical length measured by the 2 different methods for the prediction of spontaneous preterm delivery was assessed by receiver operating characteristics curve analysis. The areas under the curves were compared using a DeLong test. The predictive performance of a soft cervix (mean elastography scores with multiple of median <5th, 10th, 15th, 20th, and 25th percentile) for spontaneous preterm delivery was also determined. RESULTS: Among a total of 2316 included pregnancies, spontaneous delivery at <37 and <34 weeks' gestation occurred in 111 cases (4.8%) and 20 cases (0.9%), respectively. In the total study population, when compared with the term delivery group, the median cervical length-t was shorter in women with spontaneous delivery at <34 weeks' gestation (36.9 mm vs 35.1 mm; P=.015), but there was no clear correlation for cervical length-s. Receiver operating characteristics curves demonstrated that cervical length-t achieved better performance in predicting spontaneous delivery at <34 weeks' gestation (area under the curve, 0.658 vs 0.573; P<.01) than cervical length-s. The best combined model to predict spontaneous delivery at <34 weeks' gestation was provided by cervical length-t and history of preterm delivery (area under the curve, 0.692). In the substudy, a soft cervix with a mean elastography scores multiple of median <10th percentile had a relative risk of 7.8 (95% confidence interval, 2.1-28.6) for spontaneous delivery at <34 weeks' gestation; the detection rate was 44.4% at a false-positive rate of 9.0%. CONCLUSION: The 2-line approach provides a better estimate of the actual first-trimester cervical length and achieves better performance as a screening tool for spontaneous preterm delivery at <34 weeks' gestation than the conventional measurement. A soft cervix as determined by shear-wave elastograpthy in the first trimester is associated with an increased risk for subsequent spontaneous preterm delivery.
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Técnicas de Imagem por Elasticidade , Nascimento Prematuro , Medida do Comprimento Cervical/métodos , Colo do Útero/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Estudos ProspectivosRESUMO
Macleaya cordata extracts (MCE) are listed as feed additives in animal production by the European Food Authority. The core components of MCE are mainly sanguinarine (SA) and chelerythrine (CHE). This study aims to investigate sex differences in the pharmacokinetics and tissue residues of MCE in rats.Male and female rates were intragastrically administered MCE (1.25 mg·kg-1 body weight and 12.5 mg·kg-1 body weight dose for 28 days). SA and CHE concentrations were determined using high-performance liquid chromatography/tandem mass spectrometry.The peak plasma concentration (Cmax) and area under the curve (AUC) of both CHE and SA were higher in female than in male rats (12.5 mg·kg-1 body weight group), whereas their half-life (T1/2) and apparent volume of distribution (Vd) was lower (p < 0.05). Tissue rfesidue analysis indicated that SA and CHE were more distributed in male than in female rats and were highly distributed in the caecum and liver. SA and CHE were completely eliminated from the liver, kidney, lung, heart, spleen, leg muscle, and caecum after 120 h, indicating they did not accumulate in rats for a long time.Overall, we found that the pharmacokinetics and tissue residues of SA and CHE of male and female rats showed sex differences.
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Papaveraceae , Caracteres Sexuais , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Espectrometria de Massas , Papaveraceae/química , Extratos Vegetais , RatosRESUMO
INTRODUCTION: This study aimed to identify risk factors among maternal characteristics, obstetric history, and first trimester preeclampsia-specific biomarkers that were associated with subsequent development of gestational diabetes mellitus (GDM) and evaluate the performance of the prediction models. METHODS: This study was a secondary analysis of a prospective cohort study. The performance of the prediction models was assessed by area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 837 (8.9%) cases of GDM and 8,535 (91.1%) unaffected cases were included. The AUROC of the prediction model combining maternal characteristics and obstetric history (0.735) was better than that of the model utilizing maternal characteristics (AUROC 0.708) and preeclampsia-specific biomarkers (AUROC 0.566). Among the preeclampsia-specific biomarkers, the mean arterial pressure (MAP) contributed to the increasing risk of GDM; however, its addition did not improve the AUROC of the model combining maternal characteristics and obstetric history (0.738). CONCLUSION: The first trimester prediction model for GDM with maternal characteristics and obstetric history achieves moderate predictability. The inclusion of MAP in the model combining maternal characteristics and obstetric history does not improve the screening performance for GDM. Future studies are needed to explore the effect of blood pressure control from early pregnancy on preventing GDM.
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Diabetes Gestacional , Pré-Eclâmpsia , Biomarcadores , Diabetes Gestacional/diagnóstico , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez , Primeiro Trimestre da Gravidez , Estudos ProspectivosRESUMO
Osthol (osthole), known as a neuroprotective drug, has shown potent anticancer activity. However, the potential clinical application of osthol is limited due to its low water solubility and low bioavailability. Polybutyl cyanoacrylate (PBCA) has been widely used to improve the solubility of drugs with poor water solubility. In this study, an orthogonal experimental design (OED) was applied to design the preparation process of PBCA nanoparticles (NPs). Then, nanoparticles were prepared and evaluated in terms of physicochemical properties, in vitro release, and cellular uptake, etc. Further, the anti-cancer activity of osthol-PBCA NPs was demonstrated in SH-SY5Y cells. The pharmacokinetics and area under the curve (AUC) were investigated. The obtained osthol-NPs presented a spherical shape with a particle size of 110 ± 6.7 nm, a polydispersity index (PDI) of 0.126, and a zeta potential of −13 ± 0.32 mV. Compared with the free osthol, the drugs in osthol-NPs presented better stability and sustained release pattern activity. In vitro analysis using SH-SY5Y neuroblastoma cells showed that osthol-loaded nanoparticles displayed a significantly enhanced intracellular absorption process (three times) and cytotoxicity compared with free osthol (p < 0.05, increased 10−20%). The in vivo pharmacokinetic study revealed that the AUC of osthol-NPs was 3.3-fold higher than that of free osthol. In conclusion, osthol-PBCA NPs can enhance the bioactivity of osthol, being proposed as a novel, promising vehicle for drug delivery.
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Embucrilato , Nanopartículas , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Embucrilato/química , Portadores de Fármacos/química , Preparações de Ação Retardada , Neuroblastoma/tratamento farmacológico , Nanopartículas/química , Tamanho da Partícula , ÁguaRESUMO
BACKGROUND: The prevalence of both placenta previa and cesarean are on the rise. Multiple adverse outcomes are critically increased when placenta previa is subsequent to prior cesarean. The purpose of the present study is to develop a pre-surgical method for predicting adverse outcomes in pregnancy complicated with both placenta previa and prior cesarean. METHODS: Clinical data was obtained from the medical history system at the First Affiliated Hospital of Sun Yat-sen University from February 2003 to December 2016. All cases with a final diagnosis of "placenta previa/low lying placenta (ICD:O44.001-105)" and "scarred uterus complicated with pregnancy (ICD: O34.200-202)" were collected and reviewed. Hysterectomy was taken as the primary outcome; and blood loss was taken as the secondary outcome. RESULTS: Of 219 pregnant women in the final analysis, 25 received a hysterectomy following delivery, and 48 had blood loss exceeding 1000 ml. Pre-surgical risk factors for hysterectomy are ultrasonic signs of vascular lacunae, central placenta previa, and loss of normal hypoechoic retroplacental zone. A pre-surgical predictive equation referred to as "Hysterectomy Index in Placenta Previa with Prior cesarean (HIPs)" was generated and each risk factor was weighted to create an 8-point scale. This index yielded an area under the curve of 0.972 for the prediction of hysterectomy. CONCLUSIONS: Application of the HIPs score may provide an effective pre-surgical prediction of cesarean hysterectomy in pregnant women complicated with both placenta previa and prior cesarean.
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Histerectomia , Placenta Prévia/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Cesárea/efeitos adversos , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Curva ROC , Estudos Retrospectivos , Fatores de RiscoRESUMO
Photodynamic therapy (PDT) involves the administration and activation of photosensitizing reagents in cancer tissues to induce cytotoxicity. Here we examined the effects of 5-5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP) -mediated PDT on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line. LA795 murine lung adenocarcinoma cell line was used in the study, with cellular uptake of DTPP being quantified by a UV-visible spectrophotometer. The subcellular localization of DTPP was detected by confocal laser scanning microscopy, alteration of cell morphology after PDT was observed by an inverted light microscope, and late-stage apoptosis was examined by terminal dUTP nick end labeling (TUNEL) . The effects of influencing factors on cytotoxicity of PDT in LA795 cells was investigated with varying concentrations of DTPP, energy densities, power densities, and antioxidants by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Effects of PDT on cell cycle and plasma membrane integrity were studied by flow cytometry analysis. The uptake of DTPP by LA795 cells reached maximum after incubation for 24 h. Confocal laser scanning microscopy showed that DTPP was mainly in the mitochondrion, and slight localization was detected in the lysosomes. Cellular inhibitory effects increased with increased irradiation dose and DTPP concentration, while unactivated DTPP had low toxicity. Flow cytometry analysis revealed that DTPP-PDT-treated cells showed S phase arrest. Cell membrane damage initiation, repair, and irreversible damage were observed at 2, 4, and 5 h after DTPP-PDT , respectively. Together, our results demonstrated cell apoptosis, compromised viability, and cell cycle S phase arrest of LA795 in response to DTPP-PDT , while no effect on the lung cancer cells was observed with irradiation or photosensitizer treatment alone.
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Adenocarcinoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Forma do Núcleo Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Compostos Organofosforados , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/metabolismo , Porfirinas/metabolismoRESUMO
INTRODUCTION: Pre-eclampsia (PE) affects about 5% of Chinese pregnant women and is a major cause of maternal and perinatal morbidity and mortality. The first trimester screening model developed by the Fetal Medicine Foundation, which uses the Bayes theorem to combine maternal characteristics and medical history together with measurements of biomarkers, has been proven to be effective and has superior screening performance to that of the traditional risk factor-based approach for the prediction of PE. Prophylactic use of low-dose aspirin in women at risk for PE has resulted in a lower incidence of preterm-PE. However, there is no consensus on the preferred aspirin dosage for the prevention of preterm-PE. Evidence has also suggested that metformin has the potential benefit in preventing PE in pregnant women who are at high risk of the disorder. METHOD AND ANALYSIS: We present a protocol (V.2.0, date 17 March 2022) for the AVERT trial, which is a multicentre, double-blinded, 3-arm randomised controlled trial (RCT) that uses an effective PE screening programme to explore the optimal dosage of aspirin and the role of metformin for the prevention of PE among high-risk pregnant women in China. We intend to recruit 66 000 singleton pregnancies without treatment of low-dose aspirin and metformin at 11-13 weeks' gestation and all eligible women attending for their first trimester routine scan will be invited to undergo screening for preterm-PE by the combination of maternal factors, mean arterial pressure and placental growth factor. Women found to be at high risk of developing preterm-PE will be invited to take part in the RCT. This study will compare the incidence of preterm-PE with delivery at <37 weeks' gestation, as the primary outcome, of three different interventional groups: (1) aspirin 75 mg daily, (2) aspirin 150 mg daily and (3) aspirin 75 mg with metformin 1.5 g daily. 957 participants per treatment group are required to detect a significant difference of 59% in the reduction of the incidence of preterm-PE with 80% power and type I error of 5%. Pregnancy and neonatal outcomes will be collected and analysed. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No. 2021.406) in Hong Kong and the Ethics Committee of each participating hospital in Mainland China. The study is registered at ClinicalTrials.gov. The results of the AVERT trial will be disseminated at international academic conferences and published in high-impact factor journals. TRIAL REGISTRATION NUMBER: NCT05580523.
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Metformina , Pré-Eclâmpsia , Gravidez , Feminino , Recém-Nascido , Humanos , Aspirina , Pré-Eclâmpsia/epidemiologia , Método Duplo-Cego , China , Biomarcadores , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Although accumulated evidence supports the notion that calpain contributes to eye disease, the mechanisms by which calpain promotes RPE injury are not defined. The present study is aimed at investigating whether the effect of NaIO3-exos (exosomes derived from RPE cells under NaIO3 stimulation) on the dysfunction of the autophagy-lysosomal pathway (ALP) and apoptosis is based on its regulation of calpain activation in ARPE-19 cells and rats. The results showed that calpain-2 activation, ALP dysfunction, and apoptosis were induced by NaIO3-exos in ARPE-19 cells. NaIO3-exo significantly increased autophagic substrates by activating lysosomal dysfunction. ALP dysfunction and apoptosis in vitro could be eliminated by knocking down calpain-2 (si-C2) or the inhibitor calpain-2-IN-1. Further studies indicated that NaIO3-exo enhanced calpain-2 expression, ALP dysfunction, apoptosis, and retinal damage in rats. In summary, these results demonstrate for the first time that calpain-2 is one of the key players in the NaIO3-exo-mediated ALP dysfunction, apoptosis, and retinal damage and identify calpain-2 as a promising target for therapies aimed at age-related macular degeneration (AMD).
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Apoptose , Autofagia , Calpaína , Exossomos , Animais , Ratos , Calpaína/metabolismo , Lisossomos , Epitélio Pigmentado da Retina/metabolismoRESUMO
This study aimed to assess the feasibility of diagnosing secondary pulmonary fungal infections (PFIs) in patients with hematological malignancies (HM) using computerized tomography (CT) imaging and a support vector machine (SVM) algorithm. A total of 100 patients with HM complicated by secondary PFI underwent CT scans, and they were included in the training group. Concurrently, 80 patients with the same underlying disease who were treated at our institution were included in the test group. The types of pathogens among different PFI patients and the CT imaging features were compared. Radiomic features were extracted from the CT imaging data of patients, and a diagnostic SVM model was constructed by integrating these features with clinical characteristics. Aspergillus was the most common pathogen responsible for PFIs, followed by Candida, Pneumocystis jirovecii, Mucor, and Cryptococcus, in descending order of occurrence. Patients typically exhibited bilateral diffuse lung lesions. Within the SVM algorithm model, six radiomic features, namely the square root of the inverse covariance of the gray-level co-occurrence matrix (square root IV), the square root of the inverse covariance of the gray-level co-occurrence matrix, and small dependency low gray-level emphasis, significantly influenced the diagnosis of secondary PFIs in patients with HM. The area under the curve values for the training and test sets were 0.902 and 0.891, respectively. Therefore, CT images based on the SVM algorithm demonstrated robust predictive capability in diagnosing secondary PFIs in conjunction with HM.
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The plant species Gelsemium elegans Benth. (GEB) promotes pig and sheep growth; however, little is known about its effects in chickens. In this study, a GEB extract (GEBE) was prepared, and its effects on the growth, slaughter, antioxidant performance, meat quality, serum biochemical indices, intestinal morphology, and microflora of yellow-feathered chickens were evaluated. In total, 600 chickens aged 15 days were randomly divided into four groups with five replicates each and fed a basal diet containing 0% (control), 0.25% (0.25 GEBE), 0.75% (0.75 GEBE), or 1.25% (1.25 GEBE) GEBE until 49 days of age. Chickens were then killed, and their meat, organs, and serum and cecal contents were collected. GEBE reduced the feed conversion ratio, particularly in the 0.75 and 1.25 GEBE groups. Furthermore, the GEBE diet improved meat tenderness and reduced the meat expressible moisture content and liver malondialdehyde content, indicating high meat quality. Whereas the 0.25 GEBE diet increased the level of Lactobacillus acidophilus in the cecum, the 0.75 GEBE diet decreased the Escherichia coli level therein. These findings demonstrate that GEBE may improve the meat quality and cecal microbiota of yellow-feathered chickens, providing a basis for identifying candidate alternatives to conventional antibiotics as growth promoting feed additives.
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In the crystal of the title salt, C(26)H(34)N(2) (2+)·2I(-), the dication lies on a center of inversion that exists along the mid-point of the butyl chain; its five-membered ring is approximately planar (r.m.s. deviation = 0.011â Å). In the crystal, the iodide anion is disordered over two positions in a 1:1 ratio.
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BACKGROUND: To investigate the susceptibility of SH-SY5Y cells to DTPP-based photodynamic therapy (PDT) and the antagonistic effects of chrysophanol (Chr) on PDT. METHODS: PDT photocytotoxicity to cells was quantified and determined by exposing increasing concentrations of DTPP between 2.5 to 20 µg/mL to radiation with energy densities of 1.2-9.6 J/cm2 at 630-nm wavelength. Sodium azide (SA, NaN3) and d-mannitol (DM) were employed to study the reaction type of PDT. The photodynamic stress after PDT was assessed by superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidative capacity (T-AOC) assays. The apoptosis pathway of SH-SY5Y cells after PDT was studied by the determination of JC-1 and caspase-9/Caspase-3 concentrations. MTT and double fluorescence staining assays were applied to study the effect of Chr on cell survival and apoptosis rate in PDT, respectively. PI was used to detect the effect of Chr on cell membrane integrity after DTPP-PDT treatment. RESULTS: The dose-dependent killing effect of high DTPP concentrations and irradiation doses were identified. Cell apoptosis is mediated by a mitochondrial pathway with a total apoptosis rate of 33.8% at 10 µg/mL of DTPP after irradiation with 2.4 J/cm2. Oxidative stress was produced by ROS in PDT and non-reversible cell oxidative damage appeared due to the cells' modulation of the oxidative stress balance during the PDT response. Chr had a- effect on ROS capture and an inhibitory effect on the PDT-induced destruction of cell membranes. CONCLUSIONS: SH-SY5Y cells were susceptible to DTPP-PDT, resulting in a mitochondrial apoptosis pathway. There is an antagonistic effect of Chr on PDT in SH-SY5Y neuroblastoma cells.
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Neuroblastoma , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Apoptose , Estresse Oxidativo , Sobrevivência Celular , Espécies Reativas de Oxigênio/metabolismoRESUMO
Objective: To investigate the correlation of trends in lipid profiles from first to second trimester with trends in insulin indices and gestational diabetes mellitus (GDM). Methods: Secondary analysis of an ongoing prospective cohort study was conducted on 1234 pregnant women in a single center. Lipid profiles, glucose metabolism and insulin indices were collected in the first and second trimesters. Trends in lipid profiles were divided into four subgroups: low-to-low, high-to-high, high-to-low and low-to-high group. Insulin indices including homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were calculated to evaluate insulin resistance (IR). Trends in insulin indices were described as: no IR, persistent IR, first-trimester IR alone and second-trimester IR alone. Pearson correlation analysis and multivariate logistic regression were performed to assess the associations of lipid profiles subgroups with insulin indices and GDM. Results: First- and second-trimester total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol were strongly correlated to first- and second-trimester insulin indices. Only TG had a sustained correlation with glucose metabolism indices. High-to-high low-density lipoprotein cholesterol (LDL-c) was an independent risk factor for GDM. High-to-high TG and high-to-low TG groups were independent risk factors for persistent IR. High-to-high TG and low-to-high TG groups were independent risk factors for second-trimester IR alone. Conclusion: TG has a sustained correlation with insulin indices and glucose metabolism indices. Persistently high TG is an independent risk factor for persistent IR and second-trimester IR alone. Regardless of whether pregnant women have first-trimester IR, lower TG levels help reduce the risk for persistent IR or subsequent development of IR. These results highlight the benefit of lowering TG levels in early and middle pregnancy to prevent the development of IR.
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Diabetes Gestacional , Resistência à Insulina , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/etiologia , Insulina , Estudos Prospectivos , Colesterol , Triglicerídeos , HDL-Colesterol , GlucoseRESUMO
AIMS: To characterise retinal microvascular alterations in the eyes of pregnant patients with anaemia (PA) and to compare the alterations with those in healthy controls (HC) using optical coherence tomography angiography (OCTA). METHODS: This nested caseâcontrol study included singleton PA and HC from the Eye Health in Pregnancy Study. Fovea avascular zone (FAZ) metrics, perfusion density (PD) in the superficial capillary plexus, deep capillary plexus and flow deficit (FD) density in the choriocapillaris (CC) were quantified using FIJI software. Linear regressions were conducted to evaluate the differences in OCTA metrics between PA and HC. Subgroup analyses were performed based on comparisons between PA diagnosed in the early or late trimester and HC. RESULTS: In total, 99 eyes of 99 PA and 184 eyes of 184 HC were analysed. PA had a significantly reduced FAZ perimeter (ß coefficient=-0.310, p<0.001), area (ß coefficient=-0.121, p=0.001) and increased circularity (ß coefficient=0.037, p<0.001) compared with HC. Furthermore, higher PD in the central (ß coefficient=0.327, p=0.001) and outer (ß coefficient=0.349, p=0.007) regions were observed in PA. PA diagnosed in the first trimester had more extensive central FD (ß coefficient=4.199, p=0.003) in the CC, indicating impaired perfusion in the CC. CONCLUSION: It was found that anaemia during pregnancy was associated with macular microvascular abnormalities, which differed in PA as pregnancy progressed. The results suggest that quantitative OCTA metrics may be useful for risk evaluation before clinical diagnosis. TRIAL REGISTRATION NUMBERS: 2021KYPJ098 and ChiCTR2100049850.
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The etiology for liver cancer has been clearly defined. Unfortunately, therapeutic approaches for liver cancer are rather limited, and liver cancer is insensitive to chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) has become a promising strategy for cancer treatment as TCM elicits broad spectrum anticancer activity. In the present study, we evaluated the anticancer efficacy of AB4, an extract from the medical herb Pulsatilla chinensis (Bunge) Regel, in liver cancer in vitro and in vivo. We found that AB4 readily dose and timedependently inhibited liver cancer HepG2 and Huh7 cell proliferation and colony formation. Western blot and flow cytometry analyses suggested that AB4 treatment induced liver cancer cell apoptosis. Moreover, these findings could be readily recaptured in vivo, in which the AB4 regimen resulted in tumor suppression and cancer cell apoptosis in xenograft tumorbearing nude mice. Importantly, we noted that treatment with a Notch signaling inhibitor DAPT produced very similar anticancer efficacy in both HepG2 and Huh7 cell lines, and administration of DAPT also efficiently suppressed HepG2 xenograft outgrowth. To this end, we anticipated that AB4 and DAPT may act on the same signaling pathway, probably through inhibition of the Notch pathway. Indeed, we found decreased expression of Notch1 protein, as well as downstream targets Hes1 and Hey1, after AB4 treatment. Immunohistochemistry analysis further confirmed the suppression of Notch signaling in HepG2 xenograftbearing mice. Taken together, our study highlighted the anticancer efficacy of AB4 in liver cancer. We also provided preliminary data showing Notch as a therapeutic target of AB4. It would be interesting to investigate the anticancer efficacy of AB4 in other types of cancer with elevated Notch activity.
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Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Pulsatilla/química , Animais , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/uso terapêutico , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Receptores Notch/antagonistas & inibidores , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Organismos Livres de Patógenos Específicos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The adverse effects of sleep disorders on male fertility are of increased concern. In this study, a rat model of chronic sleep restriction (CSR) was established using the modified multiplatform method. The effects of CSR on the fertility of male rats were evaluated first based on sexual behavior. Serum hormones, including testosterone (T), prolactin (PRL), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and sperm parameters (concentration, viability, motility, deformation rate) were measured, and testicular histology was analysed by hematoxylin and eosin staining. The transcriptional differences between CSR rats and control rats were detected by RNA sequencing (RNA-Seq), and DNA methylation was then detected by bisulfite sequencing. After the differentialy expressed genes of CSR rats were sequenced and screened, representative up- and down-regulated genes were randomly sampled to verify the sequencing results by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Finally, functional annotations were completed, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomic (KEGG) pathway analyses. The results showed that the sexual behavior of CSR rats did not change when compared with control group rats. The sperm concentration, viability and motility of the CSR rats decreased significantly, while the sperm malformation rate increased significantly. In the KEGG pathway analysis database, some specific differentially expressed genes were screened, which are involved in metabolic pathways, inflammation-related pathways, the renin-angiotensin system, as well as others. However, the aforesaid differentially expressed genes in the testes were not related to their DNA methylation status. CSR could significantly reduce the fertility of male rats, and one of its mechanisms occurs by altering gene expression in the testes, which is not related to their state of DNA methylation. The results of this study suggest that CSR could cause male infertility by significantly altering the testicular transcriptome.Abbreviations: CSR: chronic sleep restriction; SD: sleep deprivation; RNA-Seq: RNA sequencing; NGS: next generation sequencing; qRT-PCR: real-time quantitative reverse transcription polymerase chain reaction; KEGG: Kyoto encyclopedia of genes and genomic; NO: nitric oxide; INOS: Inducible nitric oxide synthase; Il6: interleukin-6; Tnf: tumour necrosis factor alpha; Hsd11b1: hydroxysteroid 11-beta dehydrogenase 1; Dnmt3a: DNA methyltransferase 3Ax; PSD: paradoxic sleep deprivation; DNMTs: DNA methyltransferases family; REM: rapid eye movement sleep; PGD: preimplantation genetic diagnosis; PGS: preimplantation genetic screening; ECS: expanded carrier screening; T: testosterone; FSH: follicle stimulating hormone; LH: luteinizing hormone; PRL: prolactin; BC group: Blank Control group; MC group: Model Control group; Hist1h2ba: histone cluster 1 H2ba; Lgr4: leucine-rich repeat-containing G protein-coupled receptor 4; Atrn: attractin ; Ogg1: 8-oxoguanine DNA glycosylase; SNVs: single nucleotide variants ; HPG axis: hypothalamic-pituitary-adrenal axis; Star protein: steroid acute regulatory protein; Dmac2l: distal membrane arm assembly complex 2 like; Esr1: estrogen receptor 1; MAPK pathways: mitogen-activated protein kinase pathways; Sos2: SOS Ras/Rho guanine nucleotide exchange factor 2; Jak2: Janus kinase 2; Pik3cb: phosphatidylinositol-4,5-bisphosphate 3-kinase, and catalytic subunit beta; Kras: KRAS proto-oncogene and GTPase; RRBS: reduced representation bisulfite sequencing; DEGs: differently expressed genes; SPF: Specific Pathogen Free; HE: hematoxylin & eosin; DMR: differentially methylated region; GO Analysis: Gene Ontology analysis; SINE: short interspersed nuclear elements; LINE: long interspersed nuclear elements; LTR: long terminal repeats.
Assuntos
Regulação da Expressão Gênica/genética , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Privação do Sono/complicações , Privação do Sono/genética , Animais , Sequência de Bases , DNA/biossíntese , Metilação de DNA , Hormônios Esteroides Gonadais/sangue , Masculino , Ratos , Ratos Wistar , Comportamento Sexual Animal , Testículo/metabolismoRESUMO
To examine the difference between early kernels at different ear position in maize and the effect of nitrogen supply rates on kernel development, physiological indices in apical and mid-basal kernel 5-20 days after pollination in maize under different nitrogen supply rates (0, 120, 180 and 240 kg x ha(-1)) were determined with UV-Vis spectrophotometry. The results showed that nitrogen supply obviously increased the contents of soluble sugar, sucrose and starch, and the activities of enzymes related to sucrose inversion and starch synthesis. Twenty days after pollination, the kernel volume, dry weight and the contents of soluble sugar, sucrose and starch in apical kernel under nitrogen supply rate of 180 kg x ha(-1) were higher than those with other treatments. Five to twenty days after pollination, higher activities of acid sucrose invertase (AI), neutral sucrose invertase (NI), sucrose synthase (SS), ADPGase and starch synthase in apical kernel were also obtained under nitrogen supply rate of 180 kg x ha(-1), indicating that the sucrose utilization and starch synthesis were improved, the kernel development was promoted and the kernel abortion was reduced, which resulted in higher yield.
Assuntos
Metabolismo dos Carboidratos , Zea mays , Nitrogênio , Espectrofotometria , Amido , Sacarose , beta-FrutofuranosidaseRESUMO
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and novel therapeutic approaches are urgently required. Anemoside B4 (AB4) is a compound extracted from Pulsatilla chinensis (P. chinensis). Previous studies have indicated that P. chinensis extract P. chinensis saponins has anti-cancer activity. However, the pharmacological effect of AB4 in cancer is largely unknown. In this study, we investigated the anti-cancer efficacy of AB4 in HCC. We used CCK-8 assay and colony formation assay to evaluate the cytotoxicity of AB4 and found that this agent markedly inhibited SMMC7721 cell proliferation. By using a panel of morphological and molecular experiments, we reported that AB4 induced HCC SMMC7721 cell apoptosis and autophagy. Notably, AB4 treatment acts on the Bcl-2-caspase-3 pathway and Beclin-1-LC3-p62 pathway, thereby regulates both apoptosis and autophagy. Finally, we showed that AB4-induced apoptosis and autophagy converges at the PI3K/Akt/mTOR signaling. AB4 treatment inhibits this signaling transduction pathway and leads to HCC cell death. Collectively, our study highlighted the anti-cancer efficacy of AB4 and suggested that AB4 might be a novel way to treat HCC.