Association of cord blood Ang-1 and sCD105 levels with bronchopulmonary dysplasia in preterm infants.

BACKGROUND: To investigate the relationship between cord blood levels of Angiopoietin-1 (Ang-1) and S-endoglin (sCD105) and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Sixty-one preterm infants admitted to the neonatal intensive care unit of the study hospital between July 2021 and September 2022 were included. Cord blood was collected after the birth of premature infants. Ang-1 and sCD105 levels were quantified using the vascular endothelial growth factor enzyme-linked immunosorbent assay. Preterm infants were divided into BPD and non-BPD groups, and differences in Ang-1 and sCD105 levels between the two groups were compared. A binary logistic model was used to assess the association between low and high levels Ang-1 and BPD in preterm infants. RESULTS: In the study, there were 20 preterm infants with BPD (32.8%) and 41 preterm infants with non-BPD (67.2%). Ang-1 concentration levels were lower in the BPD group than in the non-BPD group (7105.43 (5617.01-8523.00) pg/ml vs. 10488.03 (7946.19-15962.77) pg/ml, P = 0.027). However, the sCD105 concentration levels were not significantly different between the BPD and non-BPD groups (P = 0.246). A median Ang-1 concentration of 8800.40 pg/ml was calculated. Logistic regression analysis showed that after adjusting for gestational age, birth weight, and maternal prenatal steroid hormone application, the odds ratio (OR) was 8.577 for the risk of BPD in preterm infants with Ang-1 concentrations of ≤ 8800.40 pg/ml compared to those with Ang-1 concentrations of > 8800.40 pg/ml (OR: 8.577, 95% confidence interval: 1.265-58.155, P = 0.028). CONCLUSION: Our study indicated that Ang-1 levels in the cord blood of preterm infants may be associated the risk of BPD. In the future, we will continue to conduct study with large samples.

Eating order and childhood obesity among preschoolers in China: A cross-sectional study.

Background: Early childhood is a critical period for dietary education and development of good eating habits. However, few studies have investigated the effect of eating order in children and childhood obesity in real-world settings. Objective: To examine whether the order in which meats/fish or vegetables are consumed affects the risk of obesity in preschoolers. Methods: We conducted a population-based cross-sectional study using a self-administered online survey on the lifestyle and health behaviors of preschoolers in Taizhou, China. A total of 3,200 parents were invited to take part in the survey, and 2,049 of them completed the questionnaire. Children were classified as having a normal weight, overweight, or obesity using the definitions provided by the International Obesity Task Force, and z-scores for body mass index were calculated. We divided the children's eating order at the beginning of the meal into two groups: "vegetables before meats/fish" or "meats/fish before vegetables". We analyzed the relationship between what was consumed first at a meal and the overweight status of each child. Results: No difference in body mass index was observed between the children eating meats/fish-first and the children eating vegetables-first during a meal. Children with parents who were affected by obesity were more likely to eat vegetables first. Among children of mothers with obesity, body mass index was significantly higher in the meats/fish-first group than that in the vegetable-first group (2.891 vs. 0.845, P = 0.007). In children whose mothers were affected by obesity, those that ate meats/fish first had a 12.21 times higher risk of being overweight compared with those that ate vegetables first (95% CI:1.22-121.74, P = 0.033). Conclusion: Our findings suggest eating vegetables or meats/fish at the start of a meal does not affect weight status in preschoolers.

Magnetic Resonance Imaging Evaluation of Hemangioma Resection for Encephalofacial Angiomatosis (Sturge-Weber Syndrome) in Children under Intelligent Algorithm.

This study was aimed to evaluate the clinical efficacy of hemangioma resection in the treatment of infantile encephalofacial angiomatosis (Sturge-Weber syndrome, SWS) through magnetic resonance imaging (MRI) images, and intelligent algorithms were employed to process MRI images. A retrospective study of 45 children diagnosed with facial hemangioma admitted to hospital was conducted. Then, MRS images were acquired, and a mathematical model for MRI image denoising and reconstruction was constructed based on nonlocal similar block low-rank prior algorithms. The processing effect was assessed regarding the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). Finally, MRI images were collected to analyze the difference between the metabolites of N-acetylaspartic acid (NAA), creatine (Cr), choline (Cho), and their ratios in the lesions of the children before and after treatment. The improvement rate was analyzed through a twelve-month follow-up. The algorithm test results showed that compared with the classic K-singular value decomposition (K-SVD) denoising algorithm and the Sparse MRI reconstruction algorithm, the proposed algorithm processed MRI images more clearly and had more detailed information. The quantitative results showed that the PSNR and SSIM in the image processed by the algorithm proposed were remarkably large. The clinical treatment results showed that compared with those before treatment, the nCho level after treatment, the ratio of Cho/Cr and Cho/NAA were remarkably reduced, and the difference was remarkable (P < 0.05). The follow-up results showed that the considerable improvement rate was 88.89%, the postoperative organ remodeling rate was 17.78%, and the probability of reoperation was only 6.67%. In summary, the introduction of intelligent algorithms for denoising and reconstruction of MRI images can remarkably improve image quality and help doctors use image information to diagnose diseases and evaluate treatment effects. The hemangioma resection for the treatment of pediatric SWS had a high treatment improvement rate and was worthy of clinical adoption.

Analysis of association between eating behaviours and childhood obesity among pre-school children: A cross-sectional study.

Background: Childhood obesity is a worldwide critical health concern. We aimed to clarify whether eating behaviours increased the risk of childhood obesity. Methods: We recruited 2,049 pre-school children aged 3-6 years between 1 December 2021 and 31 January 2022 in Taizhou, China. Children's weight status was classified according to the International Obesity Task Force criteria, and their eating behaviours were evaluated using the Children's Eating Behaviour Questionnaire. Correlation analyses, linear regressions, and one-way ANCOVA. were performed to analyse the association between children's eating behaviours and weight status. Results: In 'Food Avoidant' subscales, the scores of satiety responsiveness (P < 0.001) and slowness in eating (P = 0.001) were negatively associated with body mass index z score among pre-school children of both sexes. In 'Food Approach' subscales, the score of enjoyment of food was positively associated with body mass index z score in both boys (P = 0.007) and girls (P = 0.035), but the association of scores of food responsiveness with body mass index z score was found only in girls (P = 0.001). Conclusion: Our results supported that pre-school children with low scores in 'Food Avoidant' subscales and high scores in 'Food Approach' scales were more likely to become obese.

Complete mitochondrial genome and phylogenetic analysis of Schizothorax sinensis (Teleostei: Cypriniformes: Cyprinidae).

This study describes the first sequencing of the complete mitochondrial genome of Schizothorax sinensis, a species of cyprinid snowtrout from the Jialing River and Fujiang River basins in China's Sichuan Province. The total length is 16,571 base pairs. Similar to most Schizothoracinae mitochondrial genomes, there are 37 genes including 13 protein coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. In addition, it contains a control region rich in A-T nucleotides. The overall nucleotide composition is 29.6% for A, 27.1% for C, 17.9% for G and 25.4% for T, and the percentage of GC content is 45.0%. Phylogenetic analysis suggested that Schizothorax sinensis and Schizothorax prenanti clustered together in a clade. This work provides additional molecular information for studying Schizothorax sinensis conservation genetics and evolutionary relationships.

CDK7 inhibitors as anticancer drugs.

Cyclin-dependent kinase 7 (CDK7), along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs progression through the cell cycle via T-loop phosphorylation of cell cycle CDKs. CAK is also a component of the general transcription factor, TFIIH. CDK7-mediated phosphorylation of RNA polymerase II (Pol II) at active gene promoters permits transcription. Cell cycle dysregulation is an established hallmark of cancer, and aberrant control of transcriptional processes, through diverse mechanisms, is also common in many cancers. Furthermore, CDK7 levels are elevated in a number of cancer types and are associated with clinical outcomes, suggestive of greater dependence on CDK7 activity, compared with normal tissues. These findings identify CDK7 as a cancer therapeutic target, and several recent publications report selective CDK7 inhibitors (CDK7i) with activity against diverse cancer types. Preclinical studies have shown that CDK7i cause cell cycle arrest, apoptosis and repression of transcription, particularly of super-enhancer-associated genes in cancer, and have demonstrated their potential for overcoming resistance to cancer treatments. Moreover, combinations of CDK7i with other targeted cancer therapies, including BET inhibitors, BCL2 inhibitors and hormone therapies, have shown efficacy in model systems. Four CDK7i, ICEC0942 (CT7001), SY-1365, SY-5609 and LY3405105, have now progressed to Phase I/II clinical trials. Here we describe the work that has led to the development of selective CDK7i, the current status of the most advanced clinical candidates, and discuss their potential importance as cancer therapeutics, both as monotherapies and in combination settings. ClinicalTrials.gov Identifiers: NCT03363893; NCT03134638; NCT04247126; NCT03770494.

ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942.

The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become resistant to CDK7i. Resistant lines were established through continuous drug selection. ABC-transporter copy number, expression and activity were examined using real-time PCR, immunoblotting and flow cytometry. Drug responses were measured using growth assays. ABCB1 was upregulated in ICEC0942-resistant cells and there was cross-resistance to THZ1. THZ1-resistant cells upregulated ABCG2 but remained sensitive to ICEC0942. Drug resistance in both cell lines was reversible upon inhibition of ABC-transporters. CDK7i response was altered in adriamycin- and mitoxantrone-resistant cell lines demonstrating ABC-transporter upregulation. ABCB1 expression correlated with ICEC0942 and THZ1 response, and ABCG2 expression with THZ2 response, in a panel of cancer cell lines. We have identified ABCB1 upregulation as a common mechanism of resistance to ICEC0942 and THZ1, and confirmed that ABCG2 upregulation is a mechanism of resistance to THZ1. The identification of potential mechanisms of CDK7i resistance and differences in susceptibility of ICEC0942 and THZ1 to ABC-transporters, may help guide their future clinical use.

Altered expression of PGC-1α and PDX1 and their methylation status are associated with fetal glucose metabolism in gestational diabetes mellitus.

PURPOSE: To investigate the effect of gestational diabetes mellitus (GDM) on the expression and methylation of PGC-1α and PDX1 in placenta and their effects on fetal glucose metabolism. METHODS: 20 cases of full-term placenta without pregnancy complications and umbilical cord abnormalities and 20 cases of GDM group were collected. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery. DNA methylation was quantified at 7 CpG sites within the PGC-1α and PDX1 genes using PCR amplification of bisulfite treated DNA and subsequent DNA sequencing. PGC-1α and PDX1 mRNA levels were measured by reverse transcription-quantitative PCR (RT-qPCR). Meanwhile, the placental insulin, blood glucose and HbA1c levels were determined. RESULTS: The fetus birth weight and placental weight in GDM group were significantly higher than those in control group (P < 0.05). Insulin, HbA1c and blood glucose levels in GDM group were significantly higher than those in control group (P < 0.01). Insulin content was positively correlated with newborn birth weight and placental weight while HbA1c and blood glucose were positively correlated with insulin concentration (r = 0.92, P < 0.01, r = 0.85, P < 0.01). The levels of PGC-1α and PDX1 mRNA were lower in the GDM group compared to the control group. The methylation level of PGC-1α gene was higher in the GDM group compared to the control group (P < 0.05). Blood glucose was negatively correlated with the expression of PGC-1α and PDX1 mRNA in the placenta (r = -0.42, P < 0.01, r = -0.49, P < 0.01). CONCLUSION: The changes of epigenetic modification of PGC-1α gene in pregnant women with gestational diabetes mellitus may be a mechanism of abnormal glucose metabolism in offspring.

Absorption of Nasal and Bronchial Fluids: Precision Sampling of the Human Respiratory Mucosa and Laboratory Processing of Samples.

The methods of nasal absorption (NA) and bronchial absorption (BA) use synthetic absorptive matrices (SAM) to absorb the mucosal lining fluid (MLF) of the human respiratory tract. NA is a non-invasive technique which absorbs fluid from the inferior turbinate, and causes minimal discomfort. NA has yielded reproducible results with the ability to frequently repeat sampling of the upper airway. By comparison, alternative methods of sampling the respiratory mucosa, such as nasopharyngeal aspiration (NPA) and conventional swabbing, are more invasive and may result in greater data variability. Other methods have limitations, for instance, biopsies and bronchial procedures are invasive, sputum contains many dead and dying cells and requires liquefaction, exhaled breath condensate (EBC) contains water and saliva, and lavage samples are dilute and variable. BA can be performed through the working channel of a bronchoscope in clinic. Sampling is well tolerated and can be conducted at multiple sites in the airway. BA results in MLF samples being less dilute than bronchoalveolar lavage (BAL) samples. This article demonstrates the techniques of NA and BA, as well as the laboratory processing of the resulting samples, which can be tailored to the desired downstream biomarker being measured. These absorption techniques are useful alternatives to the conventional sampling techniques used in clinical respiratory research.

[Expressions of P-JNK in nerve cell apoptosis of A2AR knockout newborn mice after hypoxia/ischemia brain damage].

OBJECTIVE: To investigate the effect of adenosine A2A receptor knockout (A(2A)RKO) on relationship between continuous activation of phospho-c-Jun N-terminal kinase (P-JNK) and expression of nerve cell apoptosis in hippocampus CA1 domain of newborn mice after hypoxia/ischemia brain damage(HIBD) and its potential mechanism. METHODS: A(2A)RKO mice and adenosine A2A receptor wildtype (A(2A)RWT) littermates (n = 80) were divided into Sham operation group (S) and model group (M), 1, 3 and 7 day after HIBD, totally 8 groups. HIBD was developed with 7 day-old neonatal mice according classical Rice-Vannucci method. It was tested the effect of A(2A)RKO on short-term neurofunctional outcomes consisted of three developmental reflexes (righting, geotaxis and cliff aversion), the changes of brain pathology with hematoxylin-eosin (HE) staining and Nissl staining, the expressions of nerve cell apoptosis with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling(TUNEL) staining and P-JNK were observed by immunohistochemistry. RESULTS: The neurological behavior injuries and brain histopathological damages and nerve apoptosis cells were aggravated in A(2A)RKO newborn mice after HIBD. The positive expressions of P-JNK were significantly higher in the ischemic hippocampus CA1 domain after HIBD than ones in group S respectively (P < 0.01), reaching to peak at 1 day and then began gradually decreasing. P-JNK expression in model knockout(MKO) at 1, 3 and 7 day increased greatly compared to those in the previous time point of corresponding model wildtype (MWT) (P < 0.01, P < 0.05, P > 0.05); there was a positive correlation between the expressions of P-JNK and nerve cell apoptosis after HIBD in newborn mice(r = 0.837, P < 0.01). CONCLUSION: Early continuous activation of P-JNK might be involved in the aggravated nerve apoptosis cells and brain damage induced by A(2A) RKO newborn mice after HIBD.