Analysis of the expression level and predictive value of CLEC16A|miR-654-5p|RARA regulatory axis in the peripheral blood of patients with ischemic stroke based on biosignature analysis.

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed. Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments. Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis. Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

Effects of Maternal Health During Pregnancy and Child Immunization on Mother-to-Child Transmission of Hepatitis B Virus: A Multicentre, Large-Sample Study in Southeast China.

Purpose: High hepatitis B infection rates in China are a major public health issue, and mother-to-child transmission (MTCT) is a significant risk factor. Patients and Methods: This study was conducted with a prospective multicentre design from January 2021 to December 2022 in 245 hospitals providing midwifery services in southeastern China. The participants were pregnant women who were positive for hepatitis B surface antigen (HBs Ag) and their children. The HBs Ag concentration was tested in children aged 8-12 months. The odds ratio for each risk factor was calculated by logistic regression analysis, and the decision tree model was used. Results: A total of 5369 children born to hepatitis B-infected mothers between 8 and 12 months of age were enrolled, among whom 81 (1.51%) were positive for HBsAg. The risk factors for hepatitis B infection in 5369 children under one-year-old were a high intrauterine hepatitis B exposure level, a history of hepatitis B immunoglobulin (HBIG) delay beyond 12 hours after birth, and lack of full hepatitis B vaccine (HepB), with risks of 3.356 (1.223~9.209), 5.691 (1.931~16.773), and 5.137 (2.265~11.650), respectively. The discrimination accuracy of the decision tree was 98.5%. The risk factors for hepatitis B infection in 4542 children under one year old with high exposure risk were nonstandard treatment by the mother during pregnancy, HBIG delay beyond 12 hours after birth, and no complete HepB administration, with risks of 2.925 (1.063-8.047), 5.354 (1.806-15.871) and 5.147 (2.258-11.733), respectively. The discrimination accuracy of the decision tree was 98.3%. Conclusion: To prevent mother-to-child transmission of hepatitis B, it is necessary to standardize the treatment of pregnant women with a high exposure risk of hepatitis B, implement combined vaccination within 12 hours of birth, and standardise the full course of HepB.

Gadolinium Retention and Nephrotoxicity in a Mouse Model of Acute Ischemic Stroke: Linear Versus Macrocyclic Agents.

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, whether GBCAs and AIS would generate a synergistic negative effect remains undefined. PURPOSE: To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs. STUDY TYPE: Animal study. ANIMAL MODEL: Seventy-two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 µL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group). ASSESSMENT: Inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis. STATISTICAL TESTS: Two-way analysis of variances with post hoc Sidak's tests and independent-samples t-tests were performed. A P-value <0.05 was considered statistically significant. RESULTS: AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group. DATA CONCLUSION: AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Factors Influencing Long-Term Behavioral Intervention Outcomes in Preschool Children with Attention-Deficit Hyperactivity Disorder in Southeast China.

Introduction: Previous studies have demonstrated the long-term effectiveness of behavioral interventions for attention-deficit hyperactivity disorder (ADHD) in preschool children. We continue to design a case‒control study to further investigate the factors influencing the long-term effect of behavioral intervention. Methods: From May 2020 to August 2021, children who were newly diagnosed with ADHD and not receiving any treatment received a one-year behavioral intervention. A total of 86 children completed the behavioral intervention and assessment. Results: 50 children (58.140%) were in the effective group, and 36 children (41.860%) were in the ineffective group. Attention retention time (OR=0.559, 0.322-0.969), Swanson, Nolan, and Pelham total score (OR=1.186, 1.024-1.374) at baseline, performance score for parents (OR=0.631, 0.463-0.859), and teacher coordination (OR=0.032, 0.002-0.413) were the influencing factors of behavioral intervention effects. The area under the receiver operating curve was 0.979 (p<0.001). The comprehensive nomogram model showed that the discrimination and mean absolute error were 0.979 and 0.023, respectively. Discussion: During behavioral intervention, the implementation skills of parents should be evaluated in a timely manner. The behavioral intervention effect can be predicted based on a child's attention retention time at baseline, teacher involvement, behavioral scale score, and performance score for parents, which can guide clinicians in adjusting personalized treatment plans and provide a basis for clinical decision-making. The treatment of ADHD in preschool children requires a systematic framework that integrates family, school, and society.

Lipidomic analysis identifies long-chain acylcarnitine as a target for ischemic stroke.

INTRODUCTION: Lipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance. METHODS: Untargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes. RESULTS: Long-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage. CONCLUSION: LCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS.

Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke.

Neutrophil aggregation and clearance are important factors affecting neuroinflammatory injury during acute ischemic stroke. Emerging evidence suggests that energy metabolism is essential for microglial functions, especially microglial phagocytosis, which determines the degree of brain injury. Here, we demonstrate that Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenic acid (DHA), promotes the phagocytosis of neutrophils by microglia, thereby reducing neutrophil accumulation in the brain and alleviating neuroinflammation in the ischemic brain. Further studies reveal that RvD1 reprograms energy metabolism from glycolysis to oxidative phosphorylation (OXPHOS), providing sufficient energy for microglial phagocytosis. Moreover, RvD1 enhances microglial glutamine uptake and stimulates glutaminolysis to support OXPHOS to boost ATP production depending on adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Overall, our results reveal that RvD1 reprograms energy metabolism to promote the microglial phagocytosis of neutrophils after ischemic stroke. These findings may guide perspectives for stroke therapy from modulating microglial immunometabolism.

[Association between maternal job burnout and adolescent depression: the chain mediating effect of maternal depression and parenting style]. / æ¯äº²èŒä¸šå€¦æ€ å’Œé’å°‘å¹´æŠ‘éƒçš„å ³ç³»ï¼šæ¯äº²æŠ‘éƒå’Œæ•™å »æ–¹å¼çš„é“¾å¼ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between maternal job burnout and adolescent depression and the mediating effect of maternal depression and parenting style. METHODS: A cross-sectional study was conducted. The cluster random sampling method was used to select 2 572 adolescents from 7 middle schools in Shanghai, China, from April to May, 2021. A survey was performed for these adolescents and their mothers. The research tools included a general information questionnaire, Maslach Burnout Inventory-General Survey, Center for Epidemiologic Studies Depression Scale, short-form of Egna Minnen av Barndoms Uppfostran, and Children's Depression Inventory. A structural equation model was established, and the Bootstrap method was used to investigate the mediating effect. RESULTS: The detection rate of depressive symptoms was 12.71% (327/2 572) among the adolescents. The scores of maternal job burnout, maternal depression, and negative parenting style were positively correlated with the score of adolescent depression (P<0.05), and the score of positive parenting style was negatively correlated with the score of adolescent depression (P<0.05). Maternal depression and parenting style played a mediating role between maternal job burnout and adolescent depression, including the individual mediating effect of maternal depression, the individual mediating effect of positive parenting style, and the chain mediating effect of maternal depression-negative/positive parenting style. CONCLUSIONS: Maternal job burnout may affect adolescent depression through the mediating effect of depression, parenting style, and depression-parenting style, suggesting that the symptoms of adolescent depression can be reduced by alleviating maternal job burnout, improving maternal depression, increasing positive parenting behaviors, and reducing negative parenting behaviors.

[The influence of family structure on depression and anxiety symptoms in adolescents: the mediating role of emotional neglect]. / å®¶åº­ç»“æž„å¯¹é’å°‘å¹´æŠ‘éƒå’Œç„¦è™‘ç—‡çŠ¶çš„å½±å“ï¼šæƒ æ„Ÿå¿½è§†çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To study the influence of family structure on depression and anxiety symptoms in adolescents and its mechanism. METHODS: The cluster sampling method was used to select the students from seven middle schools in Shanghai, China. An online questionnaire survey was conducted using a self-made general status questionnaire, Childhood Trauma Questionnaire, Children's Depression Inventory, and Screen for Child Anxiety Related Emotional Disorders. The methods including one-way analysis of variance, chi-square test, binary logistic regression analysis, and mediating effect analysis were used to evaluate depression and anxiety symptoms in adolescents and the difference in childhood trauma and its mediating effect. RESULTS: Compared with the adolescents from nuclear families, the adolescents from three-generation lineal families had a lower risk of depression symptoms (OR=0.794, 95%CI: 0.649-0.972, P<0.05), while those from host families had a higher risk of depression symptoms (OR=4.548, 95%CI: 1.113-18.580, P<0.05). The adolescents from inter-generational families and host families had a significantly higher score on the Childhood Trauma Questionnaire subscale of emotional neglect (P<0.05). Emotional neglect played a mediating role in the influence of inter-generational families and host families on depression symptoms in adolescents. CONCLUSIONS: Parents and grandparents have a certain positive effect in family structures. Separation from parents may make adolescents perceive more emotional neglect, which may increase the occurrence of depression symptoms.

Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits.

PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p &lt; 0.05; gadopentetate, p &lt; 0.001) and 28 p. i of gadopentetate. (p &lt; 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p &gt; 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p &lt; 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p &lt; 0.05). CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

Effects of different grains on bacterial diversity and enzyme activity associated with digestion of starch in the foal stomach.

BACKGROUND: Compared with the stomach of ruminant cattle, the stomach of horse is small and mainly for chemical digestion, but the microorganisms in the stomach play an important role in maintaining the homeostasis of the internal environment. Due to the complexity of the microbes in the stomach, little is known about the diversity and structure of bacteria in the equine stomach. Grains are the main energy source for plant-eating livestock and energy is derived through enzymatic hydrolysis of grains into glucose or their microbial fermentation into Volatile fatty acids (VFA). However, the mechanism through which these ingested grains are chemically digested as well as the effect of these grains on the stomach remains elusive. This study explored the effects of feeding different grains (corn, oats, and barley) on bacterial diversity, structure, and composition in the foal's stomach content. Furthermore, the effects of different grains on the vitality of starch digestion-related stomach enzymes were investigated. RESULTS: No significant differences were observed (P > 0.05) in the bacterial rarefaction curves of Operational Taxonomic Units (OTUs) and diversity of the stomach microbiota in all foals. This study also revealed the statistical differences for Firmicutes, Cyanobacteria, Actinobacteria, Fibrobacteres, Lactobacillaceae, Streptococcaceae, Unidentified_Clostridiales, Prevotellaceae, Lactobacillus, Streptococcus, Unidentified_Cyanobacteria, Unidentified_Clostridiales, Lactococcus, Sphingomonas, Lactobacillus_hayakitensis, Lactobacillus_equigenerosi, and Clostridium_perfringens. The linear discriminant analysis effect size analysis revealed 9 bacteria at each classification level. The functional analysis of species information by using FAPROTAX software was able to predict 35 functions, and the top 5 functions were chemoheterotrophy, fermentation, animal_parasites_or_symbionts, nitrate_reduction, and aerobic_chemoheterotrophy. The study also revealed statistical differences for pH, glucose concentration, ß-amylase, maltase, and amylase. CONCLUSIONS: The different grains had no significant effect on the microbial diversity of the stomach content of the foal. However, the relative bacterial abundances differed significantly in response to different diets. Particularly, oats fed to the foals significantly increased the relative abundance of Firmicutes, Lactobacillaceae, Lactobacillus, and Lactobacillus_hayakitensis. The grain had no significant effect on the pH of the stomach content, glucose concentration, and enzyme viability in the foal.

The association between circadian rhythm of cortisol and shift work regularity among midwives-A multicenter study in Southeast China.

Objective: This article aims to explore the association between the trends of cortisol rhythm and the regularity of shift work among midwives. Methods: Midwives from six Southeast Chinese hospitals were recruited through cluster sampling in a multi-center cross-sectional study. Urine samples were collected half an hour after waking up, at 11:00, 19:00, and 23:00 on two consecutive days in a longitudinal cohort. The urinary cortisol was assayed by the chemiluminescence method. Results: A total of 86 midwives were included in this study, contributing 688 cortisol samples. The midwives displayed a circadian rhythm in cortisol secretion, with zeniths in the morning and nadirs in the evening. The trend of the first day was repeated on the second day. Although the total working hours per week of the two groups, namely the regular shift group (N = 43) and the irregular shift group (N = 43), were the same, significant main effects of groups (F = 62.569, p < 0.001), time (F = 45.304, p < 0.001), and group-by-time interaction (F = 226.695, p < 0.001) were indicated through linear mixed models. The main effect of day was not statistically significant, with F = 0.105 and p = 0.746. The fluctuation range of cortisol curve in the group with irregular schedules was slightly lower than that in the group with regular schedules. Conclusion: Our results may indicate that cortisol was more inhibited in midwives with irregular shift patterns than those with regular shift patterns. It is necessary to further study the relationship between cortisol rhythm and patterns of midwives' shifts in future so as to lay a foundation for hospital managers to develop a more reasonable scheduling system for midwives with the further purpose to minimize their occupational fatigue and ensure the safety of mothers and infants.

A prospective study of the decision tree prediction model for attention deficit hyperactivity disorder in preschool children. / å­¦é¾„å‰å„¿ç«¥æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å†³ç­–æ ‘é¢„æµ‹æ¨¡åž‹çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the clinical value of attention time combined with behavior scale in the screening of attention deficit hyperactivity disorder (ADHD) in preschool children. METHODS: A total of 200 preschool children with ADHD diagnosed in Fujian Maternal and Child Health Hospital from February 2019 to March 2020 were enrolled as the ADHD group. A total of 200 children who underwent physical examination in the hospital or kindergartens during the same period were enrolled as the control group. Attention time was recorded. Chinese Version of Swanson Nolan and Pelham, Version IV Scale-Parent Form (SNAP-IV) scale was used to evaluate symptoms. With clinical diagnosis as the gold standard, the decision tree analysis was used to evaluate the clinical value of attention time combined with behavior scale in the screening of ADHD. RESULTS: Compared with the control group, the ADHD group had significantly higher scores of SNAP-IV items 1, 4, 7, 8, 10, 11, 14, 15, 16, 18, 20, 21, and 22 (P<0.05) and a significantly shorter attention time (P<0.05). The variables with statistically significant differences between the two groups in univariate analysis were used as independent variables to establish a decision tree model. The accuracy of the model in predicting ADHD was 81%, that in predicting non-ADHD was 69%, and the overall accuracy was 75%, with an area under the ROC curve of 0.816 (95% CI: 0.774-0.857, P<0.001). CONCLUSIONS: The decision tree model for screening ADHD in preschool children based on attention time and assessment results of behavior scale has a high accuracy and can be used for rapid screening of ADHD among children in clinical practice.

Iptakalim improves cerebral microcirculation in mice after ischemic stroke by inhibiting pericyte contraction.

Pericytes are present tight around the intervals of capillaries, play an essential role in stabilizing the blood-brain barrier, regulating blood flow and immunomodulation, and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in ischemic stroke. We previously show that iptakalim, an ATP-sensitive potassium (K-ATP) channel opener, exerts protective effects in neurons, and glia against ischemia-induced injury. In this study we investigated the impacts of iptakalim on pericytes contraction in stroke. Mice were subjected to cerebral artery occlusion (MCAO), then administered iptakalim (10 mg/kg, ip). We showed that iptakalim administration significantly promoted recovery of cerebral blood flow after cerebral ischemia and reperfusion. Furthermore, we found that iptakalim significantly inhibited pericytes contraction, decreased the number of obstructed capillaries, and improved cerebral microcirculation. Using a collagen gel contraction assay, we demonstrated that cultured pericytes subjected to oxygen-glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation, whereas iptakalim treatment (10 µM) notably restrained pericyte contraction from 6 h during reoxygenation. We further showed that iptakalim treatment promoted K-ATP channel opening via suppressing SUR2/EPAC1 complex formation. Consequently, it reduced calcium influx and ET-1 release. Taken together, our results demonstrate that iptakalim, targeted K-ATP channels, can improve microvascular disturbance by inhibiting pericyte contraction after ischemic stroke. Our work reveals that iptakalim might be developed as a promising pericyte regulator for treatment of stroke.

Long-term effectiveness of behavioural intervention in preschool children with attention deficit hyperactivity disorder in Southeast China - a randomized controlled trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common behavioral disorder. Behavioural intervention in preschool children with ADHD is considered effective. This study discussed the long-term effectiveness of behavioural intervention in the context of nondrug therapy. METHODS: The study was a prospective, randomised controlled trial in which 201 preschoolers diagnosed with ADHD who were not receiving any treatment were assigned to two groups from January 2018 to May 2019, 101 were assigned to the conventional group and 100 to the behavioural intervention group. The behavioural intervention group included parental training, behavioural therapy, attention training, relief therapy and game therapy, in addition to the conventional group offerings. Children were evaluated at a baseline, at the end of the 12-month intervention and six months after the intervention. The primary and secondary outcome variables included attention time, the impulse-hyperactivity and hyperactivity index from Conners parent symptom questionnaire (PSQ), full-scale attention quotient (FAQ) and full-scale response control quotient (FRCQ) from integrated visual and auditory comprehensive continuous performance tests. The attention time was observed and recorded by parents, and others were performe(PSQ)d by physicians in the clinic. All statistical analyses were conducted using SPSS V26.0 (IBM), including the descriptive statistics and mixed-effects models and so on. RESULTS: The participants' mean age was (66.17±9.00) months in the behavioural group and (67.54±6.22) months in the conventional group .A total of 190 participants completed a follow-up six months after the intervention. The attention time, Conners parent symptom questionnaire (PSQ), full-scale attention quotient (FAQ) and full-scale response control quotient (FRCQ) increased significantly over time, and the behavioural group improvements were higher than those of conventional group. There was a significant main effect of time (pretest/posttest/follow-up) and group on all outcome measures (t =-12.549-4.069, p<0.05), and a significant interaction of time and group on attention time, impulsivity/hyperactivity, FAQ and FRCQ (t =-3.600-3.313, p<0.05). CONCLUSION: Behavioural intervention can effectively improve behaviour management and relieve symptoms in children with ADHD. These effects lasted at least six months. This study provides a promising approach for improving clinical efficacy with preschool children with ADHD.

Oridonin prevents oxidative stress-induced endothelial injury via promoting Nrf-2 pathway in ischaemic stroke.

Oridonin, a natural diterpenoid compound extracted from a Chinese herb, has been proved to exert anti-oxidative stress effects in various disease models. The aim of the present study was to investigate the protective effects of oridonin on oxidative stress-induced endothelial injury in ischaemic stroke. We found oridonin repaired blood-brain barrier (BBB) integrity presented with upregulation of tight junction proteins (TJ proteins) expression, inhibited the infiltration of periphery inflammatory cells and neuroinflammation and thereby reduced infarct volume in ischaemic stroke mice. Furthermore, our results showed that oridonin could protect against oxidative stress-induced endothelial injury via promoting nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2). The specific mechanism could be the activation of AKT(Ser473)/GSK3ß(Ser9)/Fyn signalling pathway. Our findings revealed the therapeutic effect and mechanism of oridonin in ischaemic stroke, which provided fundamental evidence for developing the extracted compound of Chinese herbal medicine into an innovative drug for ischaemic stroke treatment.

Effects of steam-flaked grains on foals' growth and faecal microbiota.

BACKGROUND: There is little objective information concerning the effect of steam-flaked grains on foal's growth performance and faecal microbiota. To determine the effects of steam-flaked grains on foal's growth performance and faecal microbiota, faecal samples were collection from 18 foals which had been fed either corn, oat or barley diets over the 60 days of the experiment. Body weight and conformation measurements were collected. Next-generation sequencing of the V3 + V4 region of the 16 S rRNA gene was used to assess the microbial composition of faeces. Alpha diversity, Venn graph, Relative abundance and beta diversity are presented. RESULTS: There was a significantly higher larger increase in the body weight of those foals fed barley compared to either corn or oats. There were also significant changes in the Alpha diversity of the gut microbiota. The Shannon and Simpson indices were significantly higher in the barley fed group than those fed corn or oats. The Chao1 index was significantly higher in the oat fed group than the corn or barley fed groups. There were significant changes in the relative abundance of bacteria in the microbiota in terms of phylum, family and genus. The histogram of LDA value distribution showed that the 12 statistically different biomarkers of the bacteria were present. Tax4Fun function annotation clustering heat map showed that functional information was detected from 26 species of bacteria in faecal samples from the foals. CONCLUSIONS: Differences by starch sources were found in overall growth of the foals and in the faecal microbiota if either supplementary corn, oat or barley was fed. Further studies are required to determine the potential impact of the changes in the microbiota on the health and development of foals fed cereal starch of different sources.

Network pharmacology-based exploration of therapeutic mechanism of Liu-Yu-Tang in atypical antipsychotic drug-induced metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is prevalent in patients receiving atypical antipsychotic drugs (AADs), but there are few effective interventions. The Traditional Chinese herbal decoction Liu-Yu-Tang (LYT) has achieved clinical improvement for AAD-induced MetS, but its pharmacological mechanism remains unclear. METHOD: A network pharmacology-based method was utilized in this study. First, the TCMSP and SwissTargetPrediction database were used to acquire plasma-absorbed components and putative targets of LYT, respectively. Second, an interaction network between shared targets of LYT and MetS was constructed using STRING online tool. Topological analyses were performed to extract hub gene targets. Finally, we did a pathway analysis of gene targets using the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find biological pathways of LYT. RESULTS: We obtained 655 putative targets of LYT, 434 known targets of AADs, and 1577 MetS-related gene targets. There are 232 shared targets between LYT and MetS. Interaction network construction and topological analysis yielded 60 hub targets, of which 18 were major hub targets, among which IL-6, IL-8, TNF, PI3K, MAPK, and NF-κB (RELA) are the most important in LYT's treatment of AAD-induced MetS. Pathway enrichment analysis revealed a statistically high significance of the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis and the insulin resistance pathway. CONCLUSIONS: LYT may control activities of the pro-inflammatory cytokines IL-6, IL-8, TNF and the important signal transduction molecules PI3K, MAPKs, and NF-κB (RELA), regulating metabolic disturbance-related pathways like the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis, and the insulin resistance pathway, generating therapeutic effects for AAD-induced MetS.

Iptakalim alleviates synaptic damages via targeting mitochondrial ATP-sensitive potassium channel in depression.

Synaptic plasticity damages play a crucial role in the onset and development of depression, especially in the hippocampus, which is more susceptible to stress and the most frequently studied brain region in depression. And, mitochondria have a major function in executing the complex processes of neurotransmission and plasticity. We have previously demonstrated that Iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could improve the depressive-like behavior in mice. But the underlying mechanisms are not well understood. The present study demonstrated that Ipt reversed depressive-like phenotype in vivo (chronic mild stress-induced mice model of depression) and in vitro (corticosterone-induced cellular model). Further study showed that Ipt could upregulate the synaptic-related proteins postsynaptic density 95 (PSD 95) and synaptophysin (SYN), and alleviated the synaptic structure damage. Moreover, Ipt could reverse the abnormal mitochondrial fission and fusion, as well as the reduced mitochondrial ATP production and collapse of mitochondrial membrane potential in depressive models. Knocking down the mitochondrial ATP-sensitive potassium (Mito-KATP) channel subunit MitoK partly blocked the above effects of Ipt. Therefore, our results reveal that Ipt can alleviate the abnormal mitochondrial dynamics and function depending on MitoK, contributing to improve synaptic plasticity and exert antidepressive effects. These findings provide a candidate compound and a novel target for antidepressive therapy.

Ischemic Stroke Increased Gadolinium Deposition in the Brain and Aggravated Astrocyte Injury After Gadolinium-Based Contrast Agent Administration: Linear Versus Macrocyclic Agents.

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used in MRI. However, several studies have reported Gd deposition in the brain, which has raised concerns about safety. PURPOSE: To investigate the effects of ischemic stroke on Gd deposition in the brain after repeated administration of linear or macrocyclic GBCAs and to determine whether GBCAs aggravate astrocyte injury after stroke. STUDY TYPE: Animal study. ANIMAL MODEL: Twenty-seven male Sprague-Dawley rats were randomized to an exposure group (n = 24) and a healthy control group (n = 3). Half of the exposure group (n = 12) underwent transient middle cerebral artery occlusion (tMCAO) and half (n = 12) had a sham procedure. In each subgroup (tMCAO or sham), the rats had repeated gadopentetate (n = 6) or gadobutrol (n = 6) injections. Oxygen-glucose deprivation and reoxygenation (OGD/R) was used as an in vitro model of stroke. ASSESSMENT: On day 3 and day 28 after the last injection (p.i.), the Gd concentration in the cerebrum was quantified by inductively coupled plasma mass spectrometry. Cell viability, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were analyzed in vitro. STATISTICAL TESTS: One-way analysis of variance and two-sample t-tests were performed. RESULTS: The Gd concentration in the ipsilateral hemisphere homogenates of tMCAO group was significantly higher than that in the brain homogenates of the sham group on day 3 p.i. of either gadobutrol (0.065 ± 0.006 vs. 0.042 ± 0.007 µg/g, P < 0.05) or gadopentetate (0.093 ± 0.010 vs. 0.069 ± 0.008 µg/g, P < 0.05). Increased Gd deposition was also found in the ipsilateral hemisphere homogenates of the tMCAO group compared with the brain homogenates of the sham group on day 28 p.i. of gadopentetate (0.075 ± 0.012 vs. 0.044 ± 0.003 µg/g, P < 0.05), but not gadobutrol (0.012 ± 0.007 vs. 0.010 ± 0.001 µg/g, P = 0.80). The Gd concentration in the ipsilateral hemisphere in the tMCAO group was significantly higher for gadopentetate than gadobutrol on both day 3 p.i. (0.085 ± 0.006 vs. 0.049 ± 0.005 µg/g, P < 0.05) and day 28 p.i (0.075 ± 0.012 vs. 0.012 ± 0.007 µg/g, P < 0.05). Additionally, compared with gadobutrol, gadopentetate decreased viability, increased ROS accumulation, and decreased MMP in OGD/R-induced astrocytes (all P < 0.05). DATA CONCLUSION: Administration of GBCAs after an animal model of ischemic stroke increased Gd deposition in the brain and aggravated astrocyte injury. The effect of gadopentetate appeared to be more pronounced than that of gadobutrol.

Birthweight features of the infants of mothers diagnosed with diabetes at different gestational ages in South China from 2014 to 2018: a retrospective study.

OBJECTIVES: The primary purpose was to measure the birth weight of infants of mothers with gestational diabetes (IMGDs) at different gestational ages to develop new reference charts and curves for them. A further purpose was to compare them with those of 159 334 infants in China to provide more accurate reference charts for the diagnosis of suspected abnormal birth weight of IMGDs. The final purpose was to evaluate the key periods for such mothers to control their weight in line with the difference of fetal weight of each two neighbouring gestational ages. SETTING: A specialised hospital in South China PARTICIPANTS: IMGDs born here from January 2014 to December 2018. PRIMARY AND SECONDARY OUTCOME VARIABLES: Birth weight, gestational ages of IMGDs, gender and year of birth. RESULTS: Data of 14 311 singleton live births at the gestational weeks 25-42 here were collected. The proportions of low birth weight, normal birth weight and macrosomia were 7.26%, 87.04%, and 5.70%, respectively. The proportions of small for gestational age, appropriate for gestational age and large for gestational age were 5.69%, 84.42% and 9.89%, respectively. In the macrosomia group, the mean of all birth weight in 2017 decreased for the first time since 2014. Both the means of birth weight of male infants at gestational weeks 36-41 and of female at weeks 38-40 were greater than that of the 159 334 infants. The increase of each weekly mean of IMGDs at gestational weeks 27-31 and 33-35 was >10% compared with the former. Based on this, new reference charts of birth weight for IMGDs in terms of different gestational age and gender were formulated. CONCLUSION: These charts may be applied as reference for more accurate diagnosis and quick treatment of abnormal birth weight. This study showed that the identification of key periods for fetal weight gain was helpful for the management of the weight of women with gestational diabetes.