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Fibroblast growth factor 21 (FGF21), a known risk factor for atherosclerosis, is readily regulated by exercise, and it can inhibit NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis. However, it is not clear whether aerobic exercise inhibits atherosclerosis via these pathways. Eight-week-old apolipoprotein E-deficient ( ApoE -/- ) mice on a high-fat diet were randomly divided into 1-h post-exercise (EX-1h), 24-h post-exercise (EX-24h), and sedentary (SED) groups. C57BL/6J wild-type mice fed normal chow served as controls (WT group). Mice in the EX-1h and EX-24h groups were subjected to treadmill exercise training for 12 weeks. Aerobic exercise reduced body weight; blood glucose, lipid, and inflammation levels; and aortic plaque area proportion. Aerobic exercise increased the sensitivity of FGF21 by upregulating the expression of the downstream receptor adiponectin (ApN); the serum FGF21 level after exercise increased initially, and then decreased. Aerobic exercise downregulated the expression of NLRP3 inflammasome-mediated pyroptosis-related markers in the aorta, and FGF21 may participate in the above process. Meanwhile, the liver may be the tissue source of serum FGF21 during aerobic exercise. In conclusion, aerobic exercise may inhibit atherogenesis by regulating FGF21 and NLRP3 inflammasome-mediated pyroptosis. Our study provides new information on the atherosclerosis-preventing mechanism of aerobic exercise.

Hospice care is a multidisciplinary approach that focused on patients' quality of life, and nurses allocate more of their time with patients and patients' families than those nurses working in other disciplines. Nurses' knowledge of and attitudes toward hospice care can affect the quality of hospice care. At present, China's hospice care institutions are suffering from an obvious shortage of nursing staff. Since clinical nurses are the main force behind the future provision of hospice care, their knowledge of, attitudes and willingness to practice can greatly promoted the growth of hospice care, however, available data on clinical nurses' willingness to practice hospice care are limited. A cross-sectional descriptive study design was employed to collect data from 1833 nurses working in tertiary or secondary general hospitals in Guangxi, China. We examined nurses' demographic characteristics and scores on the Chinese version of the hospice care knowledge scale, the Chinese version of the Bradley Attitude Assessment Questionnaire, and a brief quiz concerning their willingness to practice hospice care in the future. Descriptive, single factor, multiple regression analyses and logistic regression analyses were used for data analysis. Nurses displayed moderate mean scores for both knowledge of and attitudes, and only 505 (27.5%) nurses expressed their willingness to practice hospice care, 1329 (72.5%) of nurses sampled expressed their unwillingness or uncertainty. Multivariate regression analyses showed that education, professional qualification, monthly income, whether they had been trained in hospice care, and willingness to practice hospice care were the main influencing factors of knowledge; education, whether they lived with someone aged >60 years, and whether they had been trained in hospice care were main factors influencing attitudes. Additionally, logistic regression analyses showed that hospice care knowledge, whether they had been trained in hospice care, and whether they had clinical experience affected the nurses' willingness to practice hospice care. This study highlighted a knowledge gap and moderate attitudes toward hospice care among nurses, and most nurses did not prefer to practice hospice care. Having been trained in hospice care was the main common factor of nurses' knowledge of, attitudes toward, and willingness to practice hospice care in the future, indicating the necessity to provide nurses with more targeted hospice care training.

BackgroundHospice care is a multidisciplinary approach that focused on patients' quality of life, and nurses allocate more of their time with patients and patients' families than those nurses working in other disciplines. Nurses' knowledge of and attitudes toward hospice care can affect the quality of hospice care. At present, China's hospice care institutions are suffering from an obvious shortage of nursing staff. Since clinical nurses are the main force behind the future provision of hospice care, their knowledge of, attitudes and willingness to practice can greatly promoted the growth of hospice care, however, available data on clinical nurses' willingness to practice hospice care are limited.MethodsA cross-sectional descriptive study design was employed to collect data from 1833 nurses working in tertiary or secondary general hospitals in Guangxi, China. We examined nurses' demographic characteristics and scores on the Chinese version of the hospice care knowledge scale, the Chinese version of the Bradley Attitude Assessment Questionnaire, and a brief quiz concerning their willingness to practice hospice care in the future. Descriptive, single factor, multiple regression analyses and logistic regression analyses were used for data analysis.ResultsNurses displayed moderate mean scores for both knowledge of and attitudes, and only 505 (27.5%) nurses expressed their willingness to practice hospice care, 1329 (72.5%) of nurses sampled expressed their unwillingness or uncertainty. Multivariate regression analyses showed that education, professional qualification, monthly income, whether they had been trained in hospice care, and willingness to practice hospice care were the main influencing factors of knowledge; education, whether they lived with someone aged >60 years, and whether they had been trained in hospice care were main factors influencing attitudes. Additionally, logistic regression analyses showed that hospice care knowledge, whether they had been trained in hospice care, and whether they had clinical experience affected the nurses' willingness to practice hospice care.ConclusionThis study highlighted a knowledge gap and moderate attitudes toward hospice care among nurses, and most nurses did not prefer to practice hospice care. Having been trained in hospice care was the main common factor of nurses' knowledge of, attitudes toward, and willingness to practice hospice care in the future, indicating the necessity to provide nurses with more targeted hospice care training.

We explore neurodevelopmental heterogeneity in Autism Spectrum Disorder (ASD) through normative modeling of cross-cultural cohorts. By leveraging large-scale datasets from Autism Brain Imaging Data Exchange (ABIDE) and China Autism Brain Imaging Consortium (CABIC), our model identifies two ASD subgroups with distinct brain morphological abnormalities: subgroup “L” is characterized by generally smaller brain region volumes and higher rates of abnormality, while subgroup “H” exhibits larger volumes with less pronounced deviations in specific areas. Key areas, such as the isthmus cingulate and transverse temporal gyrus, were identified as critical for subgroup differentiation and ASD trait correlations. In subgroup H, the regional volume of the isthmus cingulate cortex showed a direct correlation with individuals’ autistic mannerisms, potentially corresponding to its slower post-peak volumetric declines during development. These findings offer insights into the biological mechanisms underlying ASD and support the advancement of subgroup-driven precision clinical practices. Using the lifespan brain chart and two large-scale cross-cultural consortia (ABIDE and CABIC), we disentangle the heterogeneity of brain morphology in ASD into two structural impairment pathways that could disrupt sensory to association functions.

The six-degree-of-freedom flexible joint manipulator is a complex system that suffers from the problem that the trajectory planning results are inconsistent with the control results. To keep the planned trajectory within the control range of the manipulator, a hierarchical structure control strategy is designed, which consists of a trajectory planning layer, a model predictive control layer, and a bottom control layer. Specifically, first, the target joint angles are obtained by a time-optimal trajectory planning algorithm based on a genetic algorithm in the trajectory planning layer. Second, in the model predictive control layer, considering the system physical constraints, the model predictive controller is adopted to provide the set points for the Proportion-Differentiation (PD) controllers. Finally, in the bottom control layer, the manipulator moves along the target trajectory under the PD controllers with the feedback control law. The simulation results show that, compared with the PD control strategy, the hierarchical structure control strategy can achieve better control performance and reduce the tracking error of the terminal trajectory by 33.70%.

BackgroundCongenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied.MethodsCHD cases were extracted from the China Neonatal Genomes Project (2016–2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes.ResultsIn total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05).ConclusionThis is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.

Congenital auricular deformity (CAD) is a complex phenotype that may occur as a single malformation or part of a congenital syndrome. The genetic architecture and utility of next-generation sequencing (NGS) in a sizable cross-sectional study of critically ill neonates with CAD have not yet been systematically investigated. This cross-sectional study investigated the genetic spectrum in critically ill neonates with CADs. Critically ill neonates with CADs (n = 251) were enrolled between August 8, 2016 and October 1, 2022. All neonates underwent NGS. The outcomes were molecular diagnostic yield, spectrum of genetic events, and clinical findings. Genetic findings were obtained in 107 neonates (42.6%), of which 67.3% (72/107) had pathogenic/likely pathogenic/variants of uncertain significance (P/LP/VUS) gene variations and 32.7% (35/107) had P/LP/VUS copy number variations (CNVs). The diagnostic rates of clinical exome sequencing were similar to those of exome sequencing. The logistic regression model revealed that CAD neonates with craniofacial abnormalities (OR = 4.15, 95% CI 2.29–7.53) or cardiovascular malformation (OR = 2.09, 95% CI 1.14–3.84) are more likely to be attributed to genetic causes. Follow-up analysis revealed that, compared to those in the undiagnosed group, the number of neonates whose care was withdrawn or who died was higher in the genetically diagnosed group (P < 0.05). This study identified a high incidence of genetic causes in critically ill neonates with CADs, with a combination of single-nucleotide variations and CNVs among the genetic causes of CAD. These findings highlight potential of NGS in the genetic testing of critically ill neonates with CADs.

ObjectiveTo investigate the distribution of aetiologies and outcomes in neonates with prolonged neonatal jaundice.DesignAn observational study.SettingMultiple tertiary centres from the China Neonatal Genome Project.PatientsTerm infants with jaundice lasting more than 14 days or preterm infants with jaundice lasting more than 21 days were recruited between 1 June 2016 and 30 June 2020.Main outcome measuresAetiology and outcomes were recorded from neonates with prolonged unconjugated hyperbilirubinaemia (PUCHB) and prolonged conjugated hyperbilirubinaemia (PCHB).ResultsA total of 939 neonates were enrolled, and known aetiologies were identified in 84.1% of neonates (790 of 939). Among 411 neonates with PCHB, genetic disorders (27.2%, 112 of 411) were the leading aetiologies. There were 8 deceased neonates, 19 neonates with liver failure and 12 with neurodevelopmental delay. Among 528 neonates with PUCHB, a genetic aetiology was identified in 2 of 219 neonates (0.9%) who showed disappearance of jaundice within 4 weeks of age and in 32 of 309 neonates (10.4%) with persistent jaundice after 4 weeks of age. A total of 96 of 181 neonates (53.0%) who received genetic diagnoses had their clinical diagnosis modified as a result of the genetic diagnoses.ConclusionKnown aetiologies were identified in approximately 80% of neonates in our cohort, and their overall outcomes were favourable. Genetic aetiology should be considered a priority in neonates with PCHB or the persistence of jaundice after 4 weeks of age. Moreover, genetic data can modify the clinical diagnosis and guide disease management, potentially improving outcomes.

Detect the intersect lines of multiple planes is one way to recognize and reconstruct the 3D space. First, analyzed the depth data grabbed by SR3000, sampled the depth data into gray bitmap and detect the depth gradient edge. By using the improved Hough Transformation method, get the parameters of spatial intersection lines.

Aim： To investigate the mechanisms underlying the hepatotoxicity of timosaponin A3 （TA3）, a steroidal saponin from Anemarrhena asphodeloides, in rats. Methods： Male SD rats were administered TA3 （100 mg.kg^-1·d^-1, po） for 14 d, and the blood and bile samples were collected after the final administration. The viability of a sandwich configuration of cultured rat hepatocytes （SCRHs） was assessed using WSTol. Accumulation and biliary excretion index （BEI） of d8-TCA in SCRHs were determined with LC-MS/MS. RT-PCR and Western blot were used to analyze the expression of relevant genes and proteins. ROS and ATP levels, and mitochondrial membrane potential （MMP） were measured. F-actin cytoskeletal integrity was assessed under confocal microscopy. Results： TA3 administration in rats significantly elevated the total bile acid in serum, and decreased bile acid （BA） component concentrations in bile. TA3 inhibited the viability of the SCRHs with an IC50 value of 15.21±1.73 pmol/L. Treatment of the SCRHs with TA3 （1-10 μmol/L） for 2 and 24 h dose-dependently decreased the accumulation and BEI of d8-TCA. The TA3 treatment dose- dependently decreased the expression of BA transporters Ntcp, Bsep and Mrp2, and BA biosynthesis related Cyp7a1 in hepatocytes. Furthermore, the TA3 treatment dose-dependently increased ROS generation and HO-1 expression, decreased the ATP level and MMP and disrupted F-actin in the SCRHs. NAC （5 mmol/L） significantly ameliorated TA3-induced effects in the SCRHs, whereas mangiferin （10-200 μg/mL） almost blocked TA3-induced ROS generation. Conclusion： TA3 triggers liver injury through inducing ROS generation and suppressing the expression of BA transporters. Mangiferin, an active component in Anemarrhena, may protect hepatocytes from TA3-induced hepatotoxicity.