Macrophage extracellular vesicle-packaged miR-23a-3p impairs maintenance and angiogenic capacity of human endothelial progenitor cells in neonatal hyperoxia-induced lung injury.

BACKGROUND: Premature infants requiring mechanical ventilation and supplemental oxygen for respiratory support are at increased risk for bronchopulmonary dysplasia (BPD), wherein inflammation have been proposed as a driver of hyperoxia-induced injuries, including persistent loss of endothelial progenitor cells (EPCs), impaired vascularization and eventual alveolar simplification in BPD lungs. However, the underlying mechanisms linking these phenomena remain poorly defined. METHODS: We used clodronate liposomes to deplete macrophages in a mouse model of neonatal hyperoxia-induced lung injury to evaluate if EPC loss in BPD lungs could be an effect of macrophage infiltration. We further generated in vitro culture systems initiated with cord blood (CB)-derived CD34+ EPCs and neonatal macrophages either polarized from CB-derived monocytes or isolated from tracheal aspirates of human preterm infants requiring mechanical ventilation and oxygen supplementation, to identify EV-transmitted molecular mechanism that is critical for inhibitory actions of hyperoxic macrophages on EPCs. RESULTS: Initial experiments using mouse model identified the crucial role of macrophage infiltration in eliciting significant reduction of c-Kit+ EPCs in BPD lungs. Further examination of this concept in human system, we found that hyperoxia-exposed neonatal macrophages hamper human CD34+ EPC maintenance and impair endothelial function in the differentiated progeny via the EV transmission of miR-23a-3p. Notably, treatment with antagomiR-23a-3p to silence miR-23a-3p in vivo enhances c-Kit+ EPC maintenance, and increases capillary density, and consequently mitigates simplified alveolarization in BPD lungs. CONCLUSION: Our findings highlight the importance of pulmonary intercellular communication in the pathophysiology of BPD, by identifying a linkage through vesicle transfer of miR-23a-3p from hyperoxic macrophages to EPCs, and thus demonstrating potential for novel therapeutic target in BPD.

[Clinical characteristics of Ureaplasma urealyticum infection and colonization in extremely preterm infants]. / è¶ æ—©äº§å„¿è§£è„²è„²åŽŸä½“æ„ŸæŸ“åŠå®šæ¤çŠ¶æ€çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

BaP/BPDE suppresses homologous recombination repair in human trophoblast cells to induce miscarriage: The roles of lnc-HZ08.

Benzo(a)pyrene (BaP) or benzo (a) pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE) exposure causes trophoblast cell dysfunctions and induces miscarriage, which is generally epigenetically regulated. Homologous recombination (HR) repair of DNA double strand break (DSB) plays a crucial role in maintenance of genetic stability and cell normal functions. However, whether BaP/BPDE might suppress HR repair in human trophoblast cells to induce miscarriage, as well as its epigenetic regulatory mechanism, is largely unclear. In this study, we find that BaP/BPDE suppresses HR repair of DSB in trophoblast cells and eventually induces miscarriage by up-regulating lnc-HZ08. In mechanism, lnc-HZ08 (1) down-regulates the expression levels of FOXA1 (forkhead box A1) and thus suppresses FOXA1-mediated mRNA transcription of BRCA1 (Breast cancer susceptibility gene 1) and CtIP (CtBP-interacting protein), (2) impairs BRCA1 and CtIP protein interactions by competitive binding with CtIP through lnc-HZ08-1 fragment, and also (3) suppresses BRCA1-mediated CtIP ubiquitination without affecting CtIP stability, three of which eventually suppress HR repair in human trophoblast cells. Supplement with murine Ctip could efficiently restore (i.e. increase) HR repair and alleviate miscarriage in BaP-exposed mouse model. Collectively, this study not only reveals the association and causality among BaP/BPDE exposure, the defective HR repair, and miscarriage, but also discovers novel mechanism in lnc-HZ08-regulated BRCA1/CtIP-mediated HR repair, bridging epigenetic regulation and genetic instability and also providing an efficient approach for treatment against BaP/BPDE-induced unexplained miscarriage.

Kangaroo mother care enhances exclusive breastmilk feeding and shortens time to achieve full enteral feeding in extremely preterm infants requiring non-invasive assisted ventilation.

BACKGROUND: Extremely preterm infants (EPIs) frequently encounter challenges in feeding due to their underdeveloped digestive systems. Attaining full enteral feeding at the earliest possible stage can facilitate the removal of vascular catheters and decrease catheter-related complications. METHODS: We performed a retrospective cohort study comprising 145 extremely preterm infants with a gestational age < 28 weeks who underwent non-invasive mechanical ventilation at Shenzhen Maternity & Child Healthcare Hospital between January 2019 and June 2020. The KMC group received standard nursing care along with KMC, while the control group received standard nursing care without KMC. KMC initiation took place three weeks after admission and continued for a period of two weeks or more while maintaining stable vital signs. We evaluated the rate of exclusive breastmilk feeding within 24 h prior to discharge and the time to full enteral feeding throughout hospitalization. Additionally, we conducted a multiple linear regression analysis to identify the independent factors associated with exclusive breastmilk feeding rates and the time to full enteral feeding. RESULTS: The KMC group exhibited a significantly higher rate of exclusive breastmilk feeding in the 24 h before discharge in comparison to the Non-KMC group (52.8% vs. 31.5%, OR 2.43; 95% CI 1.24, 4.78). Moreover, the KMC group achieved full enteral feeding in a shorter duration than the Non-KMC group (43.1 ± 9.6 days vs. 48.7 ± 6.9 days, p < 0.001). Multiple linear regression analysis revealed that KMC was an independent protective factor associated with improved exclusive breastmilk feeding rates (OR 2.43; 95% CI 1.24, 4.78) and a reduction in the time to full enteral feeding (ß -5.35, p < 0.001) in extremely preterm infants. CONCLUSION: Kangaroo Mother Care (KMC) can expedite the achievement of full enteral feeding and enhance exclusive breastmilk feeding rates in extremely preterm infants receiving non-invasive assisted ventilation. These findings highlight the beneficial effects of KMC on the feeding outcomes of this vulnerable population, underscoring the importance of implementing KMC as a part of comprehensive care for extremely preterm infants.

Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment.

The current research models of breast cancer are usually limited in their capacity to recapitulate the tumor microenvironment in vitro. The lack of an extracellular matrix (ECM) oversimplifies cell-cell or cell-ECM cross-talks. Moreover, the lack of tumor-associated macrophages (TAMs), that can comprise up to 50% of some solid neoplasms, poses a major problem for recognizing various hallmarks of cancer. To address these concerns, a type of direct breast cancer cells (BCCs)-TAMs coculture organoid model was well developed by a sequential culture method in this study. Alginate cryogels were fabricated with appropriate physical and mechanical properties to serve as an alternative ECM. Then, our previous experience was leveraged to polarize TAMs inside of the cryogels for creating an in vitro immune microenvironment. The direct coculture significantly enhanced BCCs organoid growth and cancer aggressive phenotypes, including the stemness, migration, ECM remodeling, and cytokine secretion. Furthermore, transcriptomic analysis and protein-protein interaction networks implied certain pathways (PI3K-Akt pathway, MAPK signaling pathway, etc.) and targets (TNF, PPARG, TLR2, etc.) during breast cancer progression in a TAM-leading immune microenvironment. Future studies to advance treatment strategies for BCC patients may benefit from using this facile model to reveal and target the interactions between cancer signaling and the immune microenvironment.

Relationship between triglyceride-glucose index baselines and trajectories with incident cardiovascular diseases in the elderly population.

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a sophisticated surrogate biomarker for insulin resistance, offering a refined means for evaluating cardiovascular diseases (CVDs). However, prospective cohort studies have not simultaneously conducted baseline and multi-timepoint trajectory assessments of the TyG index in relation to CVDs and their subtypes in elderly participants. METHODS: After excluding data deficiencies and conditions that could influence the research outcomes, this study ultimately incorporated a cohort of 20,185 participants, with data chronicles extending from 2016 to 2022. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Latent Class Trajectory Model (LCTM) was used to assess the change trends of the TyG index over multiple time points. Utilizing the Cox proportional-hazards models, we assessed the relationship between the baseline quartiles of the TyG index and various trajectories with CVDs and subtypes. RESULTS: During the mean follow-up time of 4.25 years, 11,099 patients experienced new CVDs in the elderly population. After stratifying by baseline TyG quartiles, the higher TyG level was associated with an increased risk of CVDs; the aHR and 95% CI for the highest quartile group were 1.28 (1.19-1.39). Five trajectory patterns were identified by the LCTM model. The low gradual increase group as the reference, the medium stable group, and the high gradual increase group exhibited an elevated risk of CVDs onset, aHR and 95%CIs were 1.17 (1.10-1.25) and 1.25 (1.15-1.35). Similar results were observed between the trajectories of the TyG index with subtypes of CVDs. CONCLUSION: Participants with high levels of baseline TyG index and medium stable or high gradual increase trajectories were associated with an elevated risk of developing CVDs in elderly populations.

Lung ultrasound score as a tool to predict severity of bronchopulmonary dysplasia in neonates born ≤25 weeks of gestational age.

OBJECTIVE: The primary aim was to evaluate whether the addition of the posterior lung aided in diagnostic accuracy of predicting bronchopulmonary dysplasia (BPD) vs moderate-severe BPD (msBPD); the secondary aim was to explore the diagnostic accuracy of two protocols for BPD vs msBPD. STUDY DESIGN: This was a single-center prospective observational study. Preterm infants with a gestational age ≤ 25 weeks were included. Two LUS score protocols were evaluated on the 14th day of life (DOL): (A) evaluating the anterolateral (LUS score-al) lung and (B) the anterolateral combined with posterior (LUS score-alp) lung. The LUS score range for the two protocols was 0-32 and 0-48, respectively. RESULTS: A total of eighty-nine infants were enrolled. Both the LUS score-al and LUS score-alp were higher in neonates developing BPD and msBPD than in the rest of the cohort (LUS score-al 24 (23,26) vs 22 (20,23); LUS score-alp 36 (34,39) vs 28 (25,32)) (LUS score-al 25 (24,26) vs 23 (21,24); LUS score-alp 40 (39,40) vs 34 (28,36)). The LUS score-al on the 14th DOL showed a moderate diagnostic accuracy to predict BPD and msBPD (AUC 95% CI: 0.797 [0.697-0.896]; 0.811[0.713-0.909]), while the LUS score-alp significantly improved diagnostic accuracy of BPD and msBPD (AUC 95% CI: 0.902 [0.834-0.970]; 0.922 [0.848-0.996]). A cutoff of 25 points in the LUS score-al provided a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 76.9%, 79.4%, 3.7, and 0.3 respectively to predict msBPD. Meanwhile, that of 39 points in the LUS score-alp provided a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 81%, 98.4%, 50.5 and 0.19 to predict msBPD, respectively. CONCLUSIONS: The LUS score on the 14th DOL can predict BPD and msBPD with moderate diagnostic accuracy. Apart from that, scanning posterior enhanced diagnostic accuracy.

Sex-specific association of exposure to a mixture of phenols, parabens, and phthalates with thyroid hormone and antibody levels in US adolescents and adults.

Individuals are exposed to multiple phenols, parabens, and phthalates simultaneously since they are important endocrine-disrupting compounds (EDCs) and share common exposure pathways. It is necessary to assess the effects of the co-exposure of these EDCs on thyroid hormones (THs). In this study, data included 704 adolescents and 2911 adults from the 2007-2012 National Health and Nutrition Examination Survey (NHANES). Serum THs measured total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). And 16 EDCs (3 phenols, 2 parabens, and 11 phthalates) were measured from urine. The relationship between single EDCs and single THs was analyzed using generalized linear regression. And results showed that several EDCs were positively associated with serum T3 and FT3 levels in boys but negatively associated with serum T4 and FT4 levels in girls. And in adults, five EDCs were negatively associated with T3, T4, or FT4. The effects of co-exposure to 16 EDCs on THs were calculated using Bayesian kernel machine regression and quantile-based g-computational modeling, confirmed that co-exposure was related to the increase of T3 in adolescents and the decrease of T4 in both adolescents and adults. Besides, nonlinear and linear relationships were identified between co-exposure and the risk of positive TPOAb and TgAb in girls and adult females, respectively. In conclusion, phenols, parabens, and phthalates as a mixture might interfere the concentrations of THs and thyroid autoantibodies, and the interfering effect varies significantly by sex as well as by age. Further prospective research is warranted to investigate the causal effects and underlying mechanisms of co-exposure on thyroid dysfunction.

The value of hematocrit for predicting bronchopulmonary dysplasia in very low birth weight preterm infants.

To determine hematocrit (HCT) and to identify independent risk factors for predicting bronchopulmonary dysplasia (BPD) in preterm infants with very low birth weight (VLBW) infants. This retrospective study included 296 premature infants with VLBW in the neonatal intensive care unit of the First Affiliated Hospital of the University of Science and Technology of China between January 2015 and December 2019. Maternal pregnant information and clinical information as well as hematological parameters of preterm babies were collected and compared. Then the maximum area under the curve of receiver operating characteristic curve was developed to estimate the predictive indicator in the blood. Finally, differential variables together with the predictive index were screened for multiple logistic regression analysis to determine independent prognostic factors for BPD. Infants were divided into a BPD group (134 cases) and a non-BPD group (162 cases). The area under the curve of HCT at postnatal 1 week was 0.737 with the sensitivity of 52.30 % and the specificity of 86.00%. Birth weight (BW) <1.12 kg, gestational age <28.4 weeks, newborn respiratory distress syndrome, mechanical ventilation ≥ 7 days, ventilation associated pneumonia, patent arterial duct, PaO2/FiO2 <300 mm Hg and HCT <0.455 at postnatal 1 week were risk factors for BPD of VLBW infants. HCT levels below 0.455 at 1 week after birth serve as a valuable indicator for the potential development of BPD.

Diameter of ductus arteriosus on postnatal Day 7 is associated with late pulmonary hypertension in extremely preterm infants.

OBJECTIVES: A clinically feasible biomarker for pulmonary hypertension (PH) prediction is still lacking. Thus, we aim to assess the association between ductus arteriosus (DA) diameter and PH in extremely preterm infants. STUDY DESIGN: A retrospective case-control study was performed to compare the diameter of DA in infants with and without late PH. Propensity scores were calculated to match the gestational age in two groups with a match ratio of 1:2. The diameter of DA was measured by echocardiography on postnatal Days 3 and 7. RESULTS: A total of 91 infants were included in the study. The diagnosis of late PH was made in 32 infants between postnatal life of 28-159 days. Univariable analysis showed that late PH was associated with birth weight, invasive mechanical ventilation, hemodynamically significant PDA (hsPDA), duration of PDA exposure, the rate of surgical ligation, and diameter of DA on postnatal Days 3 and 7. After adjusting for these selected factors, the diameter of DA measured on postnatal Day 7 was independently associated with the risk of late PH (odds ratios: 5.511, 95% confidence interval: 1.552-19.562, p = .008). Receiver operator curve analysis indicated that 1.95 mm in DA diameter on postnatal Day 7 was the cutoff value for late PH with an area under the curve of 0.697. CONCLUSIONS: Our findings suggest that DA diameter (larger than or equal to 1.95 mm) on postnatal Day 7 might serve as a predictor for late PH in extremely preterm infants.

Association between plasma lysophosphatidic acid levels and bronchopulmonary dysplasia in extremely preterm infants: A prospective study.

BACKGROUND: Lysophosphatidic acid (LPA) is implicated in bronchopulmonary dysplasia (BPD) pathogenesis, but clinical evidence is lacking. This study aimed to investigate LPA levels in preterm infants with and without BPD and explore LPA as a biomarker for predicting BPD occurrence. METHODS: Premature infants with a gestational age of <28 weeks or a birth weight of <1000 g were enrolled. Blood samples were collected at postnatal day (PD) 7, 28, and postmenstrual age (PMA) 36 weeks, and plasma LPA levels were measured using a commercial ELISA kit. Receiver operating characteristic curve (ROC) curve analysis determined the PD 28 cutoff for LPA, and multivariable regression analyzed LPA's independent contribution to BPD and exploratory outcomes. RESULT: Among the 91 infants enrolled in this study, 35 were classified into the non-BPD group and 56 into the BPD group. Infants with BPD had higher plasma LPA levels at PD 28 (6.467 vs. 4.226 µg/mL, p = 0.034) and PMA 36 weeks (2.330 vs. 1.636 µg/mL, p = 0.001). PD 28 LPA level of 6.132 µg/mL was the cutoff for predicting BPD development. Higher PD 28 LPA levels (≥6.132 µg/mL) independently associated with BPD occurrence (OR 3.307, 95% CI 1.032-10.597, p = 0.044). Higher LPA levels correlated with longer oxygen therapy durations [regression coefficients (ß) 0.147, 95% CI 0.643-16.133, p = .034]. CONCLUSIONS: Infants with BPD had higher plasma LPA levels at PD 28 and PMA 36 weeks. Higher PD 28 LPA levels independently associated with an increased BPD risk.

Association of Ureaplasma infection pattern and azithromycin treatment effect with bronchopulmonary dysplasia in Ureaplasma positive infants: a cohort study.

BACKGROUND: It is unclear whether Ureaplasma-associated pneumonia and azithromycin treatment affect the risk for bronchopulmonary dysplasia (BPD). METHODS: A retrospective cohort study was performed in very low birth weight (VLBW) infants who tested positive for Ureaplasma within 72 h after birth in a tertiary unit. Chest X-ray (CXR) and laboratory test were performed before and after azithromycin treatment. Multivariate logistic regression analysis was used to identify the independent association between BPD and Ureaplasma-associated pneumonia, as well as BPD and effective azithromycin treatment. RESULTS: A total of 118 infants were included in the current study, of whom 36 developed BPD (defined as supplemental oxygen needed at postmenstrual age 36 weeks or discharge). The rate of BPD was significantly higher in infants with Ureaplasma-associated pneumonia (44.6%) compared to infants with Ureaplasma colonization (17.7%, P = 0.002). After adjusting for confounders, an effective azithromycin treatment was significantly associated with reduced risk of BPD [odd ratio (OR) 0.011; 95% confidence interval (CI): 0.000-0.250), whereas Ureaplasma-associated pneumonia was not significantly associated with BPD (OR 1.835; 95% CI: 0.548-6.147). CONCLUSION: Effective Azithromycin treatment in Ureaplasma positive VLBW infants was associated with a reduced risk of BPD.

Mixed Feedings and Necrotizing Enterocolitis: The Proportion of Human Milk Matters.

Objectives: Impact of the proportion of human milk (HM) in mixed feeding on necrotizing enterocolitis (NEC) remains unknown. This study explores the influence of different proportions of HM on the risk of NEC. Materials and Methods: A retrospective cohort study was performed in infants with very low birth weight (VLBW). A spline smoothing curve was used to evaluate the dose-dependent association between HM and the risk of NEC. Univariate and multivariate analyses were performed to detect the association between the proportion of HM and NEC. Results: Twenty-four infants developed NEC, with 4 (1.9%) in the high HM group, 18 (28.1%) in the low HM group, and 2 (8.0%) in the exclusive formula group (p < 0.001). After adjusting for the relevant confounders, low HM (proportion of HM ≤54%) (OR 33.526, 95% confidential interval [CI] 7.183-156.475, p < 0.001) and exclusive formula feeding (OR 8.493, 95% CI 1.107-65.187, p = 0.040) significantly increased the incidence of NEC, compared with the high HM feeding (proportion of HM >54%). Similarly, low HM was independently associated with an increased risk of feeding intolerance compared with high HM feeding (OR 4.383, 95% CI 2.243-8.564, p < 0.001). Conclusion: A low ratio of HM (≤54%) significantly increased the risk of intestinal complications in VLBW infants. Mixed feeding should relate to the proportion of HM in premature infants.

Association of NAD+ levels with metabolic disease in a community-based study.

Background: Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and plays a crucial role in several metabolic processes. This study explored the association of nicotinamide adenine dinucleotide (NAD+) levels with metabolic disease (MD) in adults. Methods: In this cross-sectional study, all data were collected from the Jidong community. MD was defined as the presence of one or more of the following disease components: hypertension, dyslipidemia, diabetes, hyperuricemia, obesity, and non-alcoholic fatty liver disease (NAFLD). The MD components were categorized into three groups: those with one component, those with two components, and those with three to six components. The whole blood NAD+ level was measured using a cycling assay and LC-MS/MS analysis. The participants were divided into four groups based on their NAD+ level quartiles. Multivariable logistic regression was used to evaluate the association of the whole blood NAD+ levels with MD. Results: Of the 1,394 eligible participants, the average age was 43.2 years, and 74.3% had MD. In the top quartile of NAD+, the prevalence of MD and each of its components (hypertension, hyperlipidemia, diabetes, hyperuricemia, obesity, and NAFLD) were 87.9% 35.2%, 62.3%, 8.7%, 36.9%, 21.0%, and 60.5%, respectively. As compared with the lowest NAD+ quartile (≤29.4 µmol/L), the adjusted odds ratios and 95% confidence interval of the highest quartile were 3.01 (1.87-4.87) for MD, 2.48 (1.44-4.29) for 1 MD component, 2.74 (1.45-5.17) for 2 MD components, and 4.30 (2.32-7.98) for 3-6 MD components. The risk of MD began to increase at NAD+ levels of 31.0 µmol/L, as revealed by the gradient associations of NAD+ levels with MD. There was no significant interaction between age, sex, drinking, smoking, and NAD+ for MD (p for interaction ≥0.10). Conclusions: Increased NAD+ was significantly associated with MD, as well as its individual components. Our findings provide new evidence for the relationship between blood NAD+ levels and MD.

Optical Logic Gates Excited by a Gauss Vortex Interference Beam Based on Spatial Self-Phase Modulation in 2D MoS2.

Vortex beams with optical orbital angular momentum have broad prospects in future high-speed and large-capacity optical communication. In this investigation of materials science, we found that low-dimensional materials have feasibility and reliability in the development of optical logic gates in all-optical signal processing and computing technology. We found that spatial self-phase modulation patterns through the MoS2 dispersions can be modulated by the initial intensity, phase, and topological charge of a Gauss vortex superposition interference beam. We utilized these three degrees of freedom as the input signals of the optical logic gate, and the intensity of a selected checkpoint on spatial self-phase modulation patterns as the output signal. By setting appropriate thresholds as logic codes 0 and 1, two sets of novel optical logic gates, including AND, OR, and NOT gates, were implemented. These optical logic gates are expected to have great potential in optical logic operations, all-optical networks, and all-optical signal processing.

Brachial-ankle pulse wave velocity trajectories in a middle-aged population.

Objective: The "trajectory" phenotype was observed in several cardiovascular risk factors with aging. We aim to identify multiple brachial-ankle Pulse Wave Velocity (baPWV) trajectory phenotypes and assess their determinants. Methods: Among 5,182 participants with baPWV measurements (2010-2016) at no less than three time points in Kailuan Study, we derived baPWV trajectory pattern using SAS Proc Traj program. We applied the lowest Bayesian information criterion to identify the best typing model, related the identified trajectory pattern to baseline and changes in characteristics. Results: Among 5.3 ± 1.7 years follow-up, four distinct baPWV trajectories were identified as low (1,961,37.8%), medium-low (1,846,35.6%), medium-high (1,024,19.8%), and high (351,6.8%) groups. In the stepwise models, mean arterial pressure and age were the main determinators of the trajectory patterns, with a Δpseudo-R2 of 0.335 and 0.164, respectively. With the low trajectory group as reference and multivariable adjustment, odd ratios of medium low, medium high and high associated with 1 mmHg increment of mean arterial pressure were 1.08(95%CI: 1.07-1.09), 1.13(1.12-1.14), and 1.16(1.15-1.18). The estimates for age were 1.08(1.07-1.10), 1.20(1.18-1.21) and 1.28(1.26-1.31). Additionally, baseline resting heart rate, low-density lipoprotein cholesterol, fasting blood glucose, hypersensitive C-reaction protein and uric acid, and changes in mean arterial pressure, resting heart rate, fasting blood glucose, and uric acid were positively associated with the trajectory, while BMI was negatively associated. Conclusions: The changes in baPWV overtime followed a "trajectory" pattern, mainly determined by mean arterial pressure and age.

Vascular and pulmonary effects of ibuprofen on neonatal lung development.

BACKGROUND: Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD). METHODS: We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression. RESULTS: Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening. CONCLUSIONS: In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.

The regulatory roles of socio-economic status, social and intellectual activity in the relationship between alcohol consumption and cognitive decline trajectory in middle-aged and elderly Chinese: A prospective cohort study.

OBJECTIVES: To determine the relationship between alcohol consumption and cognitive decline, and to further explore the potential regulatory role of education, socio-economic status (SES), and social or intellectual activity in this relationship. METHODS: 6197 participants aged 45-75 years with four repeated measures data from 2011 to 2018 were included. A mixed-effect model was used to explore the relationship between alcohol consumption and the rate of change in cognitive decline, a latent class growth mixed model (LCGMM) was applied to determine the potential trajectory of cognitive decline, and finally, the mediating and moderating analyses were used to determine the regulatory effect of all four variables on the relationship between alcohol consumption and potential trajectory. RESULTS: Compared to never-drinkers, moderate alcohol consumption was a protective factor for overall cognitive function (ß = 0.13, 95% CI: 0.04-0.20, p < 0.001), but there was no statistical correlation with the decline rate of cognitive function. And this protective effect was no longer significant after additional adjustments for education, SES, social and intellectual activity. The LCGMM model divided participants into two trajectories, a high-level-to-decline group including 79.75% of participants (quadratic: ß [SE]: -0.90 [0.07], p < 0.001), and a low-level-to-decline group including 20.25% participants (linear: ß [SE]: -3.05 [0.49], p < 0.001). With the latter as the reference, SES played a reverse regulation role in the harmful effect of heavy drinking on cognitive trajectories (odd ratio [OR] = 0.46, 95% CI: 0.23-0.93, p < 0.05). Social and intellectual activities played a negative mediating role in the harmful effect of alcohol consumption on cognitive trajectories (light: OR = 0.96, p < 0.001; moderate: OR = 0.96, p < 0.001; heavy: OR = 0.97, p < 0.01). CONCLUSIONS: Alcohol itself has no protective effect on the decline of longitudinal cognitive trajectory. But the regulatory effect of SES, social and intellectual activities slows down the harm of alcohol consumption on the decline of cognitive function. CLINICAL TRIAL REGISTRATION: The data used in this study are from publicly available databases. They are retrospective cohort studies without any intervention. Therefore, no clinical trial registration has been conducted.

Comparing the efficacy of thyroglobulin and thyroglobulin/ thyroid-stimulating hormone ratio models in predicting a successful response to radioactive iodine therapy.

BACKGROUND: The thyroglobulin (Tg)/ thyroid-stimulating hormone (TSH) ratio has manifested to be a reliable marker for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The objective of this study was to compare the efficacy of Tg and Tg/TSH ratio models in predicting a successful response to radioactive iodine therapy. METHODS: One thousand six hundred forty-two DTC patients receiving 131I radiotherapy were finally enrolled in this retrospective study. The patients were divided into a training set (n = 973) and a validation set (n = 669) by the patient consultation time (July 2019). A receiver-operating characteristic curve was constructed for Tg and the Tg/TSH ratio to establish their cutoffs. Then, the variables were screened by univariate logistic regression and incorporated into logistic prediction models by stepwise regression, where Tg/TSH was excluded from model 1 and Tg was excluded from model 2. RESULTS: In 1642 enrolled DTC patients, the first 131I radiotherapy had an excellent response in 855 patients. The cut-offs for Tg level and Tg/TSH ratio were 3.40 ng/ mL [area under the curve (AUC): 0.789] and 36.03 ng/mIU (AUC: 0.788), respectively. In addition, the AUC of the model including Tg was higher than that of the model including Tg/TSH in both the training set (0.837 vs 0.833) and the testing set (0.854 vs 0.836). CONCLUSIONS: Both Tg and Tg/TSH ratios could be considered predictors of the effects of the first 131I ablative therapy. However, the prediction model including Tg performed better than the model including Tg/TSH.

Genome-Wide Identification and Characterization of the Trehalose-6-Phosphate Synthetase Gene Family in Chinese Cabbage (Brassica rapa) and Plasmodiophora brassicae during Their Interaction.

Trehalose is a nonreducing disaccharide that is widely distributed in various organisms. Trehalose-6-phosphate synthase (TPS) is a critical enzyme responsible for the biosynthesis of trehalose, which serves important functions in growth and development, defense, and stress resistance. Although previous studies have found that the clubroot pathogen Plasmodiophora brassicae can lead to the accumulation of trehalose in infected Arabidopsis organs, it has been proposed that much of the accumulated trehalose is derived from the pathogen. At present, there is very little evidence to verify this view. In this study, a comprehensive analysis of the TPS gene family was conducted in Brassica rapa and Plasmodiophora brassicae. A total of 14 Brassica rapa TPS genes (BrTPSs) and 3 P. brassicae TPS genes (PbTPSs) were identified, and the evolutionary characteristics, functional classification, and expression patterns were analyzed. Fourteen BrTPS genes were classified into two distinct classes according to phylogeny and gene structure. Three PbTPSs showed no significant differences in gene structure and protein conserved motifs. However, evolutionary analysis showed that the PbTPS2 gene failed to cluster with PbTPS1 and PbTPS3. Furthermore, cis-acting elements related to growth and development, defense and stress responsiveness, and hormone responsiveness were predicted in the promoter region of the BrTPS genes. Expression analysis of most BrTPS genes at five stages after P. brassicae interaction found no significant induction. Instead, the expression of the PbTPS genes of P. brassicae was upregulated, which was consistent with the period of trehalose accumulation. This study deepens our understanding of the function and evolution of BrTPSs and PbTPSs. Simultaneously, clarifying the biosynthesis of trehalose in the interaction between Brassica rapa and P. brassicae is also of great significance.