Objective To investigate serum exosomal miRNA spectrum in patients with gestational diabetes mellitus(GDM)and eval-uate its clinical value in the diagnosis of GDM complicated with premature delivery.Methods Serum samples of pregnant women with GDM registered and delivered in our hospital were collected and divided into the premature delivery group and term labor group based on pregnancy outcomes,with 22 cases in each group.Serum exosomal miRNAs were sequenced,and the differentially expressed miRNAs were further verified by fluorescence quantitative PCR.The receiver operating characteristic(ROC)curve was drew according to the verified expression level of miRNAs,and the value of exosomal miRNAs in the diagnosis of GDM complicated with premature de-livery was analyzed.The potential functions of candidate miRNAs were predicted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results A total of 94 differentially expressed miRNAs,including 50 up-regulated and 44 down-regulated,were identified in the premature delivery group and term labor group.The verification results of fluorescence quantitative PCR showed that 7 miRNAs had significant difference between the two groups(P<0.05).Moreover,the expression trend was consistent with the sequencing results.The analysis results of the ROC curve showed that the seven miRNAs had good diagnostic efficacy for GDM combined with premature delivery.The areas under the ROC curve(AUCROC)of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p were all more than 0.7.Their sensitivity and specificity were 0.375 and 1.000,0.563 and 0.941,0.563 and 0.824,and 0.765 and 0.647,respectively.The binary logistic regression analysis showed that the AUCROC of the combination of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p for the diagnosis of GDM complicated with premature delivery increased to 0.982,and that its sensi-tivity and specificity were both more than 0.850.These candidate miRNAs were related to the ubiquitin-mediated proteolysis pathway,actin cytoskeleton regulatory pathway,mTOR signaling pathway,and P53 signaling pathway.Conclusion Serum exosomal miRNAs in GDM patients complicated with premature delivery have significant difference,which may be served as potential diagnostic markers.

Objective:To evaluate any effect of transcranial direct current stimulation (tDCS) on cognitive impairment after an ischemic stroke (IS) using tract-based spatial statistics (TBSS).Methods:Fifty-one patients with mild or more serious cognitive impairment after an IS were divided into an electrical stimulation group (26 cases) and a control group (25 cases) using a random number table. In addition to conventional rehabilitation treatment, the electrical stimulation group was given tDCS, while the control group was given sham tDCS for 15 days. Before and after the treatment, both groups were evaluated using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Diffusion tensor imaging (DTI) was also performed. TBSS were computed for the differences in fractional anisotropy (FA) between the two groups before and after the treatment, and Pearson correlation analysis was applied to the pre-treatment and post-treatment FA differences within each group and the improvements in MMSE and MoCA scores.Results:After the treatment, the average MMSE and MoCA scores of both groups had improved significantly, but the improvement was significantly greater in the electrical stimulation group. After the treatment, the FA values among the electrical stimulation group had increased significantly in the bilateral genu of the corpus callosum, the bilateral inferior fronto-occipital fasciculus, the bilateral anterior thalamic radiation and the left superior longitudinal fasciculus. In the control group significant increases were recorded only in the left superior longitudinal fasciculus and the left anterior thalamic radiation. The FA change in the left superior longitudinal fasciculus of the electrical stimulation group was then positively correlated with the improvement in MMSE scores ( r=0.42), and that in the left anterior thalamic radiation was positively correlated with the improvement in MoCA scores ( r=0.45). Conclusions:tDCS can significantly improve the cognition of stroke survivors with cognitive impairment and promote the recovery of white matter fiber tracts. The FA values of the anterior thalamic radiation and the superior longitudinal fasciculus may be useful predictors and indicators of the recovery of cognitive function among such patients.

Objective To investigate serum exosomal miRNA spectrum in patients with gestational diabetes mellitus(GDM)and eval-uate its clinical value in the diagnosis of GDM complicated with premature delivery.Methods Serum samples of pregnant women with GDM registered and delivered in our hospital were collected and divided into the premature delivery group and term labor group based on pregnancy outcomes,with 22 cases in each group.Serum exosomal miRNAs were sequenced,and the differentially expressed miRNAs were further verified by fluorescence quantitative PCR.The receiver operating characteristic(ROC)curve was drew according to the verified expression level of miRNAs,and the value of exosomal miRNAs in the diagnosis of GDM complicated with premature de-livery was analyzed.The potential functions of candidate miRNAs were predicted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results A total of 94 differentially expressed miRNAs,including 50 up-regulated and 44 down-regulated,were identified in the premature delivery group and term labor group.The verification results of fluorescence quantitative PCR showed that 7 miRNAs had significant difference between the two groups(P<0.05).Moreover,the expression trend was consistent with the sequencing results.The analysis results of the ROC curve showed that the seven miRNAs had good diagnostic efficacy for GDM combined with premature delivery.The areas under the ROC curve(AUCROC)of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p were all more than 0.7.Their sensitivity and specificity were 0.375 and 1.000,0.563 and 0.941,0.563 and 0.824,and 0.765 and 0.647,respectively.The binary logistic regression analysis showed that the AUCROC of the combination of hsa-miR-16-5p,hsa-miR-25-3p,hsa-miR-30b-5p,and hsa-miR-92a-3p for the diagnosis of GDM complicated with premature delivery increased to 0.982,and that its sensi-tivity and specificity were both more than 0.850.These candidate miRNAs were related to the ubiquitin-mediated proteolysis pathway,actin cytoskeleton regulatory pathway,mTOR signaling pathway,and P53 signaling pathway.Conclusion Serum exosomal miRNAs in GDM patients complicated with premature delivery have significant difference,which may be served as potential diagnostic markers.

Objective:To evaluate any effect of transcranial direct current stimulation (tDCS) on cognitive impairment after an ischemic stroke (IS) using tract-based spatial statistics (TBSS).Methods:Fifty-one patients with mild or more serious cognitive impairment after an IS were divided into an electrical stimulation group (26 cases) and a control group (25 cases) using a random number table. In addition to conventional rehabilitation treatment, the electrical stimulation group was given tDCS, while the control group was given sham tDCS for 15 days. Before and after the treatment, both groups were evaluated using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Diffusion tensor imaging (DTI) was also performed. TBSS were computed for the differences in fractional anisotropy (FA) between the two groups before and after the treatment, and Pearson correlation analysis was applied to the pre-treatment and post-treatment FA differences within each group and the improvements in MMSE and MoCA scores.Results:After the treatment, the average MMSE and MoCA scores of both groups had improved significantly, but the improvement was significantly greater in the electrical stimulation group. After the treatment, the FA values among the electrical stimulation group had increased significantly in the bilateral genu of the corpus callosum, the bilateral inferior fronto-occipital fasciculus, the bilateral anterior thalamic radiation and the left superior longitudinal fasciculus. In the control group significant increases were recorded only in the left superior longitudinal fasciculus and the left anterior thalamic radiation. The FA change in the left superior longitudinal fasciculus of the electrical stimulation group was then positively correlated with the improvement in MMSE scores ( r=0.42), and that in the left anterior thalamic radiation was positively correlated with the improvement in MoCA scores ( r=0.45). Conclusions:tDCS can significantly improve the cognition of stroke survivors with cognitive impairment and promote the recovery of white matter fiber tracts. The FA values of the anterior thalamic radiation and the superior longitudinal fasciculus may be useful predictors and indicators of the recovery of cognitive function among such patients.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Objective:To explore whether disrupted colonization of the gut microbiota in early life accelerates the development of obesity later in life through programming adipose thermogenesis.Methods:Neonatal mice were treated with a mixture of antibiotics (ABX), and 16S rRNA sequencing confirmed that ABX treatment disrupted the establishment of gut microbiota. The mice were monitored for changes in body weight and fat content at weaning, adulthood, and under a high-fat diet (HFD) to assess obesity phenotypes. Additionally, glucose tolerance and insulin tolerance tests were conducted, along with measurements of blood glucose and lipid levels, to evaluate changes in glucose and lipid metabolism. The expression of uncoupling protein 1 (UCP1) in adipose tissue was assessed through immunohistochemistry and Western blotting to evaluate alterations in adipocyte thermogenic capacity.Results:The analysis of 16S rRNA sequencing technology revealed that ABX treatment significantly reduced both α- and β-diversity of the gut microbiota. Compared to untreated mice, the microbial composition in ABX treated mice showed significant differences, with a notable reduction in the abundance of beneficial bacteria, including Lachnospiraceae_NK4A136_group and Akkermansia muciniphila ( A. muciniphia). Subsequent monitoring indicated that ABX treatment did not affect body weight or fat content during the lactation period. However, a significant decrease in surface temperature was observed in the ABX group, specifically in the interscapular region. Immunohistochemistry and Western blot of UCP1 demonstrated impaired thermogenic capacity in adipose tissue. Interestingly, the impaired thermogenesis persisted in adult mice, leading to a decreased cold tolerance, although no changes of metabolic dysfunction, including body weight, body fat percentage, serum insulin and triglyceride levels, glucose tolerance, and insulin sensitivity. Upon switching to HFD, ABX-exposed mice exhibited significant increases in body weight, fat mass, and serum glucose, indicating a greater susceptibility to obesity. Further thermographic analysis and UCP1 detection suggested that this susceptibility to obesity was also linked to impaired thermogenic capacity in adipose tissue. Conclusion:Early-life gut microbiota is a critical determinant of long-term adipose thermogenesis. Disruption of the microbiota enhances the effect of diet-induced obesity.

Major depressive disorder (MDD), is characterized by high incidence rate, high suicide rate, and high disability rate, however, the underlying pathogenesis of MDD is still unclear. Based on the diathesis-stress model of depression, epigenetic mechanisms strongly explain the integration of genes and environment in the development of depression. However, depression has a high degree of clinical heterogeneity, with individuals of different ages presenting different symptoms and epigenetic changes. As a dynamic molecular marker that varies with age and environmental experience, epigenetics helps to elucidate the unique and complex disease pathogenesis of depression at different ages. Therefore, this paper aims to review relevant epigenetic studies of depression at different ages of onset to explore its potential age-specific association mechanism, in order to provide a theoretical basis for the formulation of accurate intervention measures for patients with MDD at different ages.

Major depressive disorder (MDD), is characterized by high incidence rate, high suicide rate, and high disability rate, however, the underlying pathogenesis of MDD is still unclear. Based on the diathesis-stress model of depression, epigenetic mechanisms strongly explain the integration of genes and environment in the development of depression. However, depression has a high degree of clinical heterogeneity, with individuals of different ages presenting different symptoms and epigenetic changes. As a dynamic molecular marker that varies with age and environmental experience, epigenetics helps to elucidate the unique and complex disease pathogenesis of depression at different ages. Therefore, this paper aims to review relevant epigenetic studies of depression at different ages of onset to explore its potential age-specific association mechanism, in order to provide a theoretical basis for the formulation of accurate intervention measures for patients with MDD at different ages.

This paper aims to explore the main points of diagnosis， treatment and misdiagnosis of conversion disorder characterized by paroxysmal abdominal pain. The general hospitals had a high misdiagnose rate and no effective symptomatic treatment for conversion disorder patients with physical discomfort as main symptoms， which leading to heavy physical and mental burden of patients and waste of medical resources， so this paper retrospectively analyzed the etiology， diagnostic process， treatment and therapeutic effect of a case of conversion disorder with paroxysmal abdominal pain as the main symptom. Case analysis showed that the physical discomfort as chief complain of conversion disorder patients affected the rate of early correct diagnosis and treatment， so clinicians' ability of diagnosis and differential diagnosis of conversion disorder needs to be strengthened. At the same time， cognitive behavioral therapy （CBT） is effective in the clinical treatment and recurrence prevention of conversion disorder.

Patients with major depressive disorder (MDD) have a cognitive impairment, and part of the cognitive impairment persists in the remission stage, which restricts the overall patient's comprehensive recovery. Brain-derived neurotrophic factor (BDNF) and its related gene expression play important roles in neuronal genesis, synaptic plasticity and dendritic growth in the brain, and are closely related to the pathogenesis of MDD and its cognitive impairment. Therefore, this article reviews the latest research on the mechanism of cognitive impairment of MDD affected by BDNF from the aspects of gene inheritance, such as BDNF expression, gene polymorphism and epigenetic inheritance, in order to provide a theoretical basis for further exploring the mechanism of cognitive impairment of MDD.