Predicting autism spectrum disorder using maternal risk factors: A multi-center machine learning study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090). The extreme gradient boosting model performed best, achieving an accuracy of 66.2 % on the external cohort from three cities (ASD:266, TD:353). The most important risk factors were identified as unstable emotions and lack of multivitamin supplementation using Shapley values. ASD risk scores were calculated based on predicted probabilities from the optimal model and divided into low, medium, and high-risk groups. The logistic analysis indicated that the high-risk group had a significantly increased risk of ASD compared to the low-risk group. Our study demonstrated the potential of machine learning models in predicting the risk for ASD based on maternal factors. The developed model provided insights into the maternal emotion and nutrition factors associated with ASD and highlighted the potential clinical applicability of the developed model in identifying high-risk populations.

Intestinal Symptoms Among Children aged 2-7 Years with Autism Spectrum Disorder in 13 Cities of China.

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. METHODS: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. RESULTS: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. CONCLUSION: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.

Understanding green loyalty: A literature review based on bibliometric-content analysis.

Green loyalty is a crucial factor that influences consumers' purchase intentions and is essential for the sustainable development of ecological environments. However, research on this topic is still scattered, and exploring the research hotspots and trends of green loyalty is vital for future studies. This systematic literature review clarified the conceptual content, structure, and measurement of green loyalty. Additionally, the study conducted a bibliometric analysis of 236 articles on green loyalty from 2002 to 2022 in the Web of Science database. The content analysis revealed the theoretical basis, antecedent and outcome variables, and mechanisms of green loyalty, providing important guidance for future research.

High-normal unconjugated bilirubin is associated with decreased risk of chronic kidney disease in type 2 diabetes: A real-world study.

OBJECTIVE: To investigate the association between serum unconjugated bilirubin (UCB) within normal limits and chronic kidney disease (CKD) in T2DM patients. METHOD: This cross-sectional, real-world study was performed in 8661 hospitalised T2DM patients. The subjects were stratified into quintiles based on serum UCB levels. The clinical characteristics and CKD prevalence were compared among the UCB quantile groups. The associations of serum UCB levels and quintiles with CKD were also analysed by binary logistic regression. RESULTS: After controlling for age, sex, and diabetes duration (DD), the CKD prevalence (20.4%, 12.2%, 10.6%, 8.3%, and 6.4% for the first, second, third, fourth, and fifth quintiles, respectively, p < 0.001 for trend) was significantly decreased across the serum UCB quintiles. The fully adjusted regression model showed negative associations of serum UCB levels (OR: 0.660, 95% CI: 0.585-0.744; p < 0.001 for trend) and quintiles (p < 0.001) with the presence of CKD. Compared with the subjects in the lowest UCB quintile, the risk of CKD decreased by 36.2%, 54.3%, 53.8%, and 62.1%, respectively, in those from the second to the highest UCB quintile. Additionally, C-reactive protein (CRP) levels were significantly higher in the subjects with CKD than in those without CKD (p < 0.001), and significantly decreased across the UCB quintiles (p < 0.001 for trend). CONCLUSIONS: Serum UCB levels within the normal range were significantly and negatively linked to CKD in T2DM patients. High-normal UCB may be an independent protective factor for CKD by its antioxidant and the following anti-inflammatory activities through its signalling activity, which was indicated by clearly decreased CRP levels across the UCB quintiles.

CHOP promotes coelomocyte apoptosis through p38-MAPK pathway in Vibrio splendidus-challenged sea cucumber Apostichopus japonicus.

CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) belongs to the C/EBP family of transcription factors that has been proven to regulate apoptosis in many vertebrate species. However, the functional role of CHOP in invertebrates is largely unknown. In this paper, the open reading frame of CHOP was cloned and characterized in the sea cucumber Apostichopus japonicus (AjCHOP). The deuced amino acid of AjCHOP shared a conserved RTP801_C domain from 63 to 171 aa. Phylogenetic analysis indicated that AjCHOP clustered with CHOPs from Lytechinus variegatus and Strongylocentrotus purpuratus. To confirm the immune function of AjCHOP, the time-course expression profiles of AjCHOP were investigated, and the findings revealed AjCHOP was significantly induced in coelomocytes at mRNA and protein levels after Vibro splendidus challenge. Furthermore, knockdown of AjCHOP in coelomocyes by siRNA transfection significantly decreased the apoptosis level induced by V. splendidus. Mechanically, AjCHOP-mediated apoptosis was dependent on the activation of p38-MAPK pathway but not JNK/ERK-MAPK. Overall, our results supported that V. splendidus triggers apoptosis among the coelomocytes, whereas AjCHOP mediates through the p38-MAPK pathway in A. japonicus.

Association of feeding patterns in infancy with later autism symptoms and neurodevelopment: a national multicentre survey.

BACKGROUND: We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. METHODS: We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. RESULTS: Children with ASD had a shorter breastfeeding duration in infancy (8 (3-12) months vs. 10 (6-14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4-6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance. CONCLUSIONS: Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than TD children. These feeding patterns may be related to the symptoms and growth of children with ASD. The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms and that infants who have difficulty introducing complementary foods should be followed up for neurodevelopment. TRIAL REGISTRATION: The ethics committee of the Children's Hospital of Chongqing Medical University approved the study. Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194, registered on 23/03/2020).

Enhanced efficiency of calcium-derived oleoyl serine on osteoporosis via Wnt/ß-catenin pathway.

Osteoporosis is a common disease of the elderly that affects millions of patients worldwide. It is mainly characterized by low bone mineral density and increased risk of fracture due to the deterioration of the bone structure, leading to difficulties in functional recovery, reduced quality of life, increased disability risk and mortality in the population. It has already been a major public health problem. Osteoporosis is a chronic disease that is difficult to treat in the elderly population, so it is crucial to develop new drugs for the treatment of osteoporosis. Oleoyl serine, an endogenous fatty acyl amide found in bone, has been shown to have excellent anti-osteoporosis effects, but it is easily hydrolyzed by amidases in vivo. The aim of this study is to determine the anti-osteoporotic effect of calcium-derived oleoyl serine, a novel oleoyl serine derivative and the molecular mechanism underneath. In vitro experiments demonstrated that calcium-derived oleoyl serine suppressed the expression of Fabp4, and Cebpα while Alp, and Runx2 was significantly upregulated compared with the oleoyl serine group and control. With the activation of ß-catenin, calcium-derived oleoyl serine restored the abnormal osteogenesis and lipogenesis, indicating calcium-derived oleoyl serine compared with oleoyl serine has better effects on promoting osteogenesis and suppressing lipogenesis. In vivo experiment agreed with these findings that calcium-derived oleoyl serine promotes osteogenesis and suppresses its lipogenesis to ameliorate osteoporosis via a ß-catenin dependent method. It is a new candidate for treating osteoporosis.

Effect of medical researchers' creative performance on scientific misconduct: a moral psychology perspective.

BACKGROUND: In recent years, some researchers have engaged in scientific misconduct such as fabrication, falsification, and plagiarism to achieve higher research performance. Considering their detrimental effects on individuals' health status (e.g., patients, etc.) and extensive financial costs levied upon healthcare systems, such wrongdoings have even more salience in medical sciences. However, there has been little discussion on the possible influence of medical researchers' existing creative performance on scientific misconduct, and the moral psychological mechanisms underlying those effects are still poorly understood. METHODS: We build a moderated mediation model to test how medical researchers' creative performance affects their scientific misconduct and explore the role of moral licensing and moral identity in this process. Based on situational experiments and projection techniques, 287 medical researchers in China participated in a survey. RESULTS: Medical researchers' creative performance positively relates to scientific misconduct, and moral licensing plays a mediating role in the relationship between them. In addition, moral identity has a negative moderating effect on the mediating effect of moral licensing on creative performance and scientific misconduct. CONCLUSION: Moral licensing plays a fully mediating role in the relationship between creative performance and scientific misconduct. And moral identity negatively moderates the indirect effect of creative performance on scientific misconduct through moral licensing. The findings provide theoretical and practical implications for the prevention of medical researchers' scientific misconduct.

Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes.

Purpose: The association between serum osteocalcin (OCN) levels and metabolic dysfunction-associated fatty liver disease (MAFLD) is still controversial. Moreover, few studies have explored their relationship in type 2 diabetes mellitus (T2DM) patients so far. The present study aimed to investigate the association of serum OCN levels with MAFLD in Chinese T2DM patients. Methods: This cross-sectional, real-world study included 1889 Chinese T2DM inpatients. MAFLD was diagnosed by abdominal ultrasonography. Participants were divided into four groups according to serum OCN quartiles, among which the clinical characteristics were compared. The association of serum OCN levels with the presence of MAFLD was also analyzed in subjects. Results: After controlling for sex, age, and diabetes duration, the prevalence of MAFLD significantly decreased across the serum OCN quartiles (55.3%, 52.0%, 48.6%, and 42.1% for the first, second, third, and fourth quartiles, respectively, P < 0.001 for trend). A fully adjusted multiple logistic regression analysis showed that serum OCN levels were independently and negatively associated with the presence of MAFLD in T2DM patients (odds ratio, 0.832; 95% confidence interval, 0.719-0.962; P = 0.013). Furthermore, there were significant decreases in HOMA-IR (P = 0.001 for trend) and C-reactive protein (P < 0.001 for trend) levels across the serum OCN quartiles after controlling for sex, age, and diabetes duration. Conclusion: Serum OCN levels were independently and negatively associated with the presence of MAFLD in Chinese T2DM patients, partially due to the improvement of insulin resistance and inflammation mediated by OCN. Serum OCN may be used as a biomarker to assess the risk of MAFLD in T2DM patients.

Low-normal serum unconjugated bilirubin levels are associated with late but not early carotid atherosclerotic lesions in T2DM subjects.

Aims: We aimed to examine the association of serum unconjugated bilirubin (UCB) within normal limits with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, real-world study was performed in 8,006 hospitalized T2DM patients including 4,153 men and 3,853 women with normal UCB. The subjects were stratified into quintiles based on serum UCB levels (<6.2, 6.2-7.9, 8.0-8.9, 9.0-10.9, and >10.9 µmol/l, respectively). Carotid atherosclerotic lesions detected by ultrasonography, including carotid intima-media thickness (CIMT), carotid plaque, and stenosis, were compared among the five groups. The associations of serum UCB levels and quintiles with carotid atherosclerotic lesions were also determined by multiple logistic regression. Results: The prevalence of carotid plaque (55.3%, 49.5%, 47.4%, 43.8%, and 37.5%, respectively; p < 0.001 for trend) and stenosis (15.2%, 12.2%, 9.1%, 7.7%, and 5.4%, respectively; p < 0.001 for trend) was progressively lower across the UCB quintiles even after adjusting for age, sex, and duration of diabetes. Results of a fully adjusted multiple logistic regression analysis revealed that serum UCB levels and quintiles were significantly associated with carotid plaque and stenosis. Compared with the subjects in the lowest UCB quintile, the risk of carotid plaque decreased by 25.5%, 28.7%, 33.5%, and 42.8%, and that of carotid stenosis by 24.6%, 37.4%, 44.9%, and 47.3%, respectively, in those from the second to highest UCB quintiles. High serum UCB within the normal range was a protective factor against carotid plaque [odds ratio (OR) 0.810, 95% confidence interval (CI) 0.747-0.878; p < 0.001] and stenosis [OR 0.722, 95% CI 0.647-0.805; p < 0.001]. However, no significant association was observed between serum UCB and CIMT in T2DM patients. Furthermore, C-reactive protein (CRP) levels were significantly higher in the subjects with carotid atherosclerosis than in those without carotid atherosclerosis and clearly decreased across the UCB quintiles. Conclusions: Serum UCB within normal limits is inversely associated with late carotid atherosclerotic lesions including carotid plaque and stenosis but not CIMT, an early carotid atherosclerotic lesion in T2DM patients. High-normal UCB may be protective against carotid atherosclerosis by its anti-inflammation effect, which was indicated by significantly decreased CRP levels from the lowest to highest UCB quintiles.

Waist-to-height ratio is a simple and practical alternative to waist circumference to diagnose metabolic syndrome in type 2 diabetes.

Background: As an indicator of abdominal obesity, waist circumference (WC) varied with race and gender in diagnosing metabolic syndrome (MetS). Therefore, it is clinically important to find an alternative indicator of abdominal obesity independent of these factors to diagnose MetS. Our aims were to evaluate the association between waist-to-height ratio (WHtR) and MetS and further determine whether WHtR could be used as a simple and practical alternative to WC to diagnose MetS in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, real-world study recruited 8488 hospitalized T2DM patients including 3719 women (43.8%) aged from 18 to 94 years and 4769 men (56.2%) aged from 18 to 91 years. A WHtR cut-off of 0.52 was used to diagnose MetS in both men and women T2DM patients based on our previous study. The association of WHtR with MetS in T2DM patients was analyzed by binary logistic regression. The consistency of two diagnostic criteria for MetS according to WC and WHtR was determined by Kappa test. Results: The prevalence of MetS according to WHtR was 79.4% in women and 68.6% in men T2DM patients, which was very close to the prevalence of MetS according to WC in both women (82.6%) and men (68.3%). The prevalence of MetS diagnosed by WC in both men and women with WHtR ≥ 0.52 was significantly higher than in those with WHtR < 0.52 after adjustment for age and duration of diabetes (89.2 vs. 38.7% for men; 92.8 vs. 57.4% for women; respectively, all p < 0.001). Binary logistic regression analysis displayed that after adjusting for confounding factors, WHtR was significantly associated with the presence of MetS in both men and women (men: OR = 4.821, 95% CI: 3.949-5.885; women: OR = 3.096, 95% CI: 2.484-3.860; respectively, all p < 0.001). Kappa test revealed that there was an excellent consistency between the diagnosis of MetS based on WC and on WHtR in T2DM patients (men: kappa value = 0.929, 95% CI: 0.918-0.940; women: kappa value = 0.874, 95% CI: 0.854-0.894; total: kappa value = 0.911, 95% CI: 0.901-0.921; respectively, all p < 0.001). Conclusion: WHtR is independently associated with the presence of MetS and can be used as a simple and practical alternative to WC to diagnose MetS regardless of gender in T2DM patients.

GA/HbA1c ratio is a simple and practical indicator to evaluate the risk of metabolic dysfunction-associated fatty liver disease in type 2 diabetes: an observational study.

BACKGROUND: It is still debatable whether glycated albumin/glycated hemoglobin A1C (GA/HbA1C) ratio is associated with metabolic dysfunction-associated fatty liver disease (MAFLD), and few studies have been conducted in type 2 diabetes mellitus (T2DM). Therefore, we aimed to investigate the association between GA/HbA1C ratio and MAFLD and to evaluate whether GA/HbA1C ratio can be used an indicator of MAFLD in Chinese patients with T2DM. METHODS: This cross-sectional study consisted of 7117 T2DM patients including 3296 men and 3821 women from real-world settings. Abdominal ultrasonography was performed to diagnose MAFLD. In addition to comparing the clinical characteristics among the GA/HbA1C ratio quartile groups, we also investigated the associations of GA/HbA1C ratio and quartiles with MAFLD in T2DM subjects. RESULTS: There was a significantly decreased trend in the MAFLD prevalence across the GA/HbA1C ratio quartiles (56.3%, 47.4%, 37.8%, and 35.6% for the first, second, third, and fourth quartile, respectively, P < 0.001 for trend) after adjusting for gender, age, and diabetes duration. Fully adjusted Binary logistic regression indicated that both GA/HbA1C ratio (OR: 0.575, 95% CI: 0.471 to 0.702, P < 0.001) and quartiles (P < 0.001 for trend) were inversely associated with the presence of MAFLD among T2DM patients. Additionally, HOMA2-IR values were clearly increased in the T2DM subjects with MAFLD compared with those without MAFLD (P < 0.001), and markedly increased from the highest to the lowest GA/HbA1C ratio quartile (P < 0.001 for trend). CONCLUSIONS: GA/HbA1C ratio is closely and negatively associated with MAFLD in T2DM subjects, which may attribute to that GA/HbA1C ratio reflects the degree of insulin resistance. GA/HbA1C ratio may act as a simple and practical indicator to evaluate the risk of MAFLD in T2DM.

Early life exposure to triclosan from antimicrobial daily necessities may increase the potential risk of autism spectrum disorder: A multicenter study in China.

BACKGROUND: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention. OBJECTIVE: The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children. METHODS: A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS. RESULTS: Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted ß = 0.277, P < 0.001). TCS concentration was higher in ASD children (P = 0.005), and positively correlated with ABC (Sensory subscales: P = 0.03; Social self-help subscales: P = 0.011) and SRS scale scores (Social awareness subscales: P = 0.045; Social communication subscales: P = 0.001; Autism behavior mannerisms subscales: P = 0.006; SRS total score: P = 0.003) in ASD children. This association was more pronounced in boys than in girls. CONCLUSION: To our knowledge, this is the first case-control study to examine the correlation between TCS and ASD. Our results suggest that maternal UADN during pregnancy may be a potential risk of ASD in offspring. Further detection of TCS levels showed that maternal UADN during pregnancy may be associated with excessive TCS exposure. In addition, the level of TCS in children with ASD is higher than TD children. The higher levels of TCS in children with ASD may be significantly associated with more pronounced core symptoms, and this association was more significant in male children with ASD.

Vitamin D status is primarily associated with core symptoms in children with autism spectrum disorder: A multicenter study in China.

OBJECTIVE: We aimed to investigate the relationship between vitamin D status and core symptoms and neurodevelopmental levels in children with ASD with a multicenter survey. METHODS: We enrolled 1321 ASD children and 1279 typically developing (TD) children aged 2-7 years from 13 cities in China. ASD symptoms were assessed with the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS), and neurodevelopmental levels were evaluated with the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). RESULTS: Children with ASD had lower serum 25(OH)D levels than TD children. Serum 25(OH)D levels were negatively associated with CARS and communication warning behavior of CNBS-R2016 scores, and were not associated with the development quotients of ASD children. ASD Children were grouped based on the quartiles for 25(OH)D levels in the controls, and children in the first to third quartiles had higher SRS social communication and/or CARS and communication warning behavior of CNBS-R2016 scores than those in the fourth quartile. CONCLUSIONS: Serum 25(OH)D levels were primarily associated with core symptoms in children with ASD, and individuals with relatively lower 25(OH)D levels displayed worse autistic symptomatology. More research is needed to determine whether vitamin D supplements would be a useful treatment for ASD.

Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study.

Aims: There is still a debate about the relationship between serum iron and metabolic dysfunction-associated fatty liver disease (MAFLD). Furthermore, few relevant studies were conducted in type 2 diabetes mellitus (T2DM). Therefore, this study aimed to explore the association of serum iron levels with MAFLD in Chinese patients with T2DM. Methods: This cross-sectional, real-world study consisted of 1,467 Chinese T2DM patients. MAFLD was diagnosed by abdominal ultrasonography. Based on serum iron quartiles, the patients were classified into four groups. Clinical characteristics were compared among the four groups, and binary logistic analyses were used to assess the associations of serum iron levels and quartiles with the presence of MAFLD in T2DM. Results: After adjusting for gender, age, and diabetes duration, significantly higher prevalence of MAFLD was found in the second (45.7%), third (45.2%), and fourth (47.0%) serum iron quartiles than in the first quartiles (26.8%), with the highest MAFLD prevalence in the fourth quartile (p < 0.001 for trend). Moreover, increased HOMA2-IR (p = 0.003 for trend) and decreased HOMA2-S (p = 0.003 for trend) were observed across the serum iron quartiles. Fully adjusted binary logistic regression analyses indicated that both increased serum iron levels (OR: 1.725, 95% CI: 1.427 to 2.085, p < 0.001) and quartiles (p < 0.001 for trend) were still closely associated with the presence of MAFLD in T2DM patients even after controlling for multiple confounding factors. Conclusions: There is a positive correlation between the presence of MAFLD and serum iron levels in T2DM patients, which may be attributed to the close association between serum iron and insulin resistance. Serum iron levels may act as one of the indicators for evaluating the risk of MAFLD in T2DM individuals.

Neurodevelopmental domain characteristics and their association with core symptoms in preschoolers with autism spectrum disorder in China: a nationwide multicenter study.

BACKGROUND: Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. METHODS: We enrolled 1019 ASD preschoolers aged 2-7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. RESULTS: Based on general developmental quotient (GQ) < 70, 68.4% of the preschoolers with ASD had a developmental delay (DD), rated mild in 32.7% of them. The highest DD rate (> 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55-69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. CONCLUSIONS: Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. TRIAL REGISTRATION: ChiCTR2000031194 , registered on 03/23/2020.

Vitamin A Status Is More Commonly Associated With Symptoms and Neurodevelopment in Boys With Autism Spectrum Disorders-A Multicenter Study in China.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and show a striking male bias in prevalence. Vitamin A (VA) is essential for brain development, and abnormalities in its metabolite retinoic acid are associated with the pathophysiology of ASD. This national multicenter study was conducted to investigate the relationship between serum VA level and core symptoms in ASD children and whether there are still sex differences. Method: A total of 1,300 children with ASD and 1,252 typically-developing (TD) controls aged 2-7 years old from 13 cities in China were enrolled in this study. The symptoms of children with ASD were evaluated by the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS). The neurodevelopmental level of the children was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). The serum level of VA was measured by high-performance liquid chromatography (HPLC). Results: The serum VA level in children with ASD was significantly lower than that in TD children, especially in boys with ASD. Furthermore, VA levels in male children with ASD were lower than those in female children with ASD. In addition, we found that serum VA level was negatively correlated the SRS, CARS and communication warming behavior of CBNS-R2016 scores in boys with ASD. In terms of developmental quotients, serum VA level was positively associated with the general quotient, language quotient, gross motor quotient and personal-social quotient of boys with ASD, but no difference was found in girls with ASD. Conclusions: ASD children, especially boys, have lower serum VA levels than TD children. Moreover, serum VA status is more commonly associated with clinical symptoms and neurodevelopment in boys with ASD.

Sex Differences in Diurnal Sodium Handling During Diet-Induced Obesity in Rats.

BACKGROUND: Emerging evidence over the past several years suggests that diurnal control of sodium excretion is sex dependent and involves the renal endothelin system. Given recent awareness of disruptions of circadian function in obesity, we determined whether diet-induced obesity impairs renal handling of an acute salt load at different times of day and whether this varies by sex and is associated with renal endothelin dysfunction. METHODS: Male and female Sprague-Dawley rats were placed on a high-fat diet for 8 weeks before assessing renal sodium handling and blood pressure. RESULTS: Male, but not female, rats on high fat had a significantly reduced natriuretic response to acute NaCl injection at the beginning of their active period that was associated with lower endothelin 1 (ET-1) excretion, lower ET-1 mRNA expression in the cortex and outer medulla as well as lower ETB receptor expression in the outer medulla of the high-fat rats. Obese males also had significantly higher blood pressure (telemetry) that was exacerbated by adding high salt to the diet during the last 2 weeks. While female rats developed hypertension with a high-fat diet, they were not salt sensitive and ET-1 excretion was unchanged. CONCLUSIONS: These data identify diet-induced obesity as a sex-specific disruptive factor for maintaining proper sodium handling. Although high-fat diets induce hypertension in both sexes, these data reveal that males are at greater risk of salt-dependent hypertension and further suggest that females have more redundant systems that can be productive against salt-sensitive hypertension in at least some circumstances.

Possible Catch-Up Developmental Trajectories for Children with Mild Developmental Delay Caused by NAA15 Pathogenic Variants.

Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three de novo variants and one maternal variant. The in vitro minigene splicing assay confirmed one noncanonical splicing variant (c.1410+5G>C), which resulted in abnormal mRNA splicing. All affected children presented mild developmental delay, and catch-up trajectories were noted in three patients based on their developmental scores at different ages. Meanwhile, the literature review also showed that half of the reported patients with NAA15 variants presented mild/moderate developmental delay or intellectual disability, and possible catch-up sign was indicated for three affected patients. Taken together, our study expanded the spectrum of NAA15 variants in NDD patients. The affected patients presented mild developmental delay, and possible catch-up developmental trajectories were suggested. Studying the natural neurodevelopmental trajectories of NDD patients with pathogenic variants and their benefits from physical rehabilitations are needed in the future for precise genetic counseling and clinical management.

A Multi-Center Study on the Relationship Between Developmental Regression and Disease Severity in Children With Autism Spectrum Disorders.

Introduction: This study aimed to investigate the prevalence of developmental regression in children with Autism Spectrum Disorder (ASD) and to explore its relationship with disease severity. Methods: We finally included 1,027 ASD children aged 2-5 years from 13 cities in China: 138 with regressive ASD and 889 with non-regressive ASD. The Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) were used to evaluate the core symptoms and developmental status of children in the two groups. Results: Among the 1,027 ASD children eventually included, 138 (13.44%) cases showed regressive behavior and the average regression occurring age was 24.00 (18.00-27.00) months. Among the regressive children, 105 cases (76.09%) had language regression, 79 cases (57.25%) had social regression, and 4 cases (2.90%) had motor regression. The total scores of ABC and the sub-score of sensory and stereotypic behavior (ß = 5.122, 95% CI: 0.818, 9.426, P < 0.05; ß = 1.104, 95% CI: 0.120, 2.089, P < 0.05; ß = 1.388, 95% CI: 0.038, 2.737, P < 0.05), the SRS total scores and the sub-score of autistic mannerisms (ß = 4.991, 95% CI: 0.494, 9.487, P < 0.05; ß = 1.297, 95% CI: 0.140, 2.453, P < 0.05) of children in the regressive group were all higher than the non-regressive group. The total developmental quotient (DQ) of CNBS-R2016 and the DQ of gross motor, fine motor, adaptive behavior, language (ß = -5.827, 95% CI: -11.529, -0.125, P < 0.05) and personal society in the regressive group were lower than the non-regressive group and the proportion of children with intelligent developmental impairment was higher the non-regressive group. Conclusion: Regressive autism is mainly manifested as language and social regression. Children with regressive ASD have more severe core symptoms, lower neurodevelopmental level DQ, and more serious disease degree than children with non-regressive ASD, which requires further etiological examinations and more clinical attention.