The total alkaloids of Sophora alopecuroides L. improve depression-like behavior in mice via BDNF-mediated AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression has become a global public health problem and the development of new highly effective, low-toxicity antidepressants is imminent. Sophora alopecuroides L. is a common medicinal plant, which has therapeutic effect on central nervous system diseases. AIM OF THE STUDY: In this study, the antidepressant effect of total alkaloids (ALK) isolated from Sophora alopecuroides L. was explored and the mechanism was further elucidated. MATERIALS AND METHODS: A primary neuronal injury model was established in vitro by corticosterone. ICR mice were then selected to construct an in vivo model of chronic unpredictable mild stress (CUMS)-induced depression, and the ameliorative effects of ALK on depression were examined by various behavioral tests. The antidepressant molecular mechanism of ALK was subsequently revealed by ELISA, Western blot, immunohistochemistry and Golgi staining. RESULTS: BDNF secretion as well as TrkB and ERK phosphorylated protein levels were found to be improved in primary cortical neurons, along with improved dendritic complexity of neurons. The results of in vivo showed that the depression-like behavior of CUMS-induced mice was reversed after 2 weeks of continuous gavage administration of ALK, and the neurotransmitter levels in the plasma of mice were increased. Moreover, the expression levels of key proteins of BDNF-AKT-mTOR pathway and the complexity of neuronal dendrites were improved in the prefrontal cortex of mice. CONCLUSIONS: These findings indicate that ALK of Sophora alopecuroides L. can effectively improve the depressive phenotype of mice, possibly by promoting the expression of BDNF in prefrontal cortex, activating the downstream AKT/mTOR signal pathway, and ultimately enhancing neuronal dendritic complexity.

Matrine alleviates depressive-like behaviors via modulating microbiota-gut-brain axis in CUMS-induced mice.

BACKGROUND: The realization of the "microbiota-gut-brain" axis plays a critical role in neuropsychiatric disorders, particularly depression, is advancing rapidly. Matrine is a natural bioactive compound, which has been found to possess potential antidepressant effect. However, the underlying mechanisms of regulation of the "microbiota-gut-brain" axis in the treatment of depression by oral matrine remain elusive. METHODS: Its antidepressant effects were initially evaluated by behavioral tests and relative levels of monoamine neurotransmitters, and matrine has been observed to attenuate the depression-like behavior and increase neurotransmitter content in CUMS-induced mice. Subsequently, studies from the "gut" to "brain" were conducted, including detection of the composition of gut microbiota by 16S rRNA sequencing; the metabolomics detection of gut metabolites and the analysis of differential metabolic pathways; the assessment of relative levels of diamine oxidase, lipopolysaccharide, pro-inflammatory cytokines, and brain-derived neurotrophic factor (BDNF) by ELISA kits or immunofluorescence. RESULTS: Matrine could regulate the disturbance of gut microbiota and metabolites, restore intestinal permeability, and reduce intestinal inflammation, thereby reducing the levels of pro-inflammatory cytokines in peripheral blood circulation and brain regions, and ultimately increase the levels of BDNF in brain. CONCLUSION: Matrine may ameliorate CUMS-induced depression in mice by modulating the "microbiota-gut-brain" axis.

Topological Alterations of the Brain Functional Network in Type 2 Diabetes Mellitus Patients With and Without Mild Cognitive Impairment.

The aim of this study was to explore the topological alterations of the brain functional network in type 2 diabetes mellitus (T2DM) patients with and without mild cognitive impairment (MCI) using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory approaches. In total, 27 T2DM patients with MCI, 27 T2DM patients without MCI, and 27 healthy controls (HCs) underwent rs-fMRI scanning. The whole-brain functional network was constructed by thresholding the Pearson's correlation matrices of 90 brain regions. The topological organization of the constructed networks was analyzed by using graph theory approaches. The global and nodal properties of the participants in the three groups were compared by using one-way ANOVA as well as post hoc Tukey's t-tests. The relationships between the altered topological properties and clinical features or scores of neuropsychological tests were analyzed in T2DM patients with MCI. At the global level, the global and local efficiency of the patients in the T2DM with MCI group were significantly higher than that of participants in the HCs group, and the length of the characteristic path was significantly lower than that of the participants in the HCs group (p < 0.05). No significant difference was found among the other groups. At the nodal level, when compared with T2DM patients without MCI, T2DM patients with MCI showed significantly increased nodal centrality in four brain regions, which were mainly located in the orbitofrontal lobe and anterior cingulate gyrus (ACG) (p < 0.05). No significant difference was found between the T2DM patients without MCI and HCs. Moreover, nodal degree related coefficient (r = -0381, p = 0.050) and nodal efficiency (r = -0.405, P = 0.036) of the ACG showed a significant closed correlation with the scores of the digit span backward test in the T2DM patients with MCI. Our results suggested that the increased nodal properties in brain regions of the orbitofrontal lobe and ACG were biomarkers of cognitive impairment in T2DM patients and could be used for its early diagnosis. The global topological alterations may be related to the combination of MCI and T2DM, rather than any of them.

Correlation between Lactobacillus and expression of E-cadherin, ß-catenin, N-cadherin, and Vimentin in postmenopausal cervical lesions.

BACKGROUND: To detect the correlation between Lactobacillus vaginalis and the expression of epithelial-mesenchymal transition (EMT)-related factors, E-cadherin, ß-catenin, N-cadherin, and Vimentin, in postmenopausal cervical squamous intraepithelial lesions (SILs) and cervical squamous cell carcinoma (SCC), and to explore the possible mechanism. METHODS: From January 2016 to January 2020, 30 postmenopausal patients with low-grade SIL (LSIL), 18 patients with high-grade SIL (HSIL), and 30 patients with SCC who underwent colposcopy biopsy in the Outpatient Department of the First Affiliated Hospital of Inner Mongolia Medical University were selected as the experimental group, and 30 postmenopausal normal women were selected as the control group. The expression of 16SrRNA of Lactobacillus vaginalis in each group was determined by the 16S third-generation full-length amplification sequencing technique. The mRNA expression levels of E-cadherin, ß-catenin, N-cadherin, and Vimentin were detected by quantitative real-time polymerase chain reaction (qPCR). The correlation between the 16SrRNA expression level of Lactobacillus vaginalis and the mRNA expression level of the EMT-related proteins was compared among all groups. RESULTS: (I) The progression of postmenopausal cervical SILs to cervical SCC was significantly positively correlated with age, number of pregnancies, smoking, pH value, positive rate of HPV16, and negatively correlated with total Lactobacillus 16SrRNA expression (P<0.0001). (II) The level of vaginal microbiota in postmenopausal women showed that Lactobacillus iners was dominant. With the progression of the disease, the expression levels of 16SrRNA in Lactobacillus iners and Lactobacillus total vagina decreased gradually, and the differences were statistically significant (P<0.05). (III) With the disease progresses. The expression of total Lactobacillus 16SrRNA was positively correlated with the mRNA expression of ß-catenin and E-cadherin (r>0; P<0.05), and negatively correlated with the mRNA expression of Vimentin and N-cadherin (r<0; P<0.05). CONCLUSIONS: In postmenopausal women, Lactobacillus vaginalis interacts with HPV and is associated with the occurrence of EMT, promoting the development of cervical lesions.

Beneficial Effect of Alkaloids From Sophora alopecuroides L. on CUMS-Induced Depression Model Mice via Modulating Gut Microbiota.

It was recently shown that the gut microbiota of both depression patients and depression model animals is significantly altered, suggesting that gut microbes are closely related to depression. Here, we investigated the effects of Sophora alopecuroides L.-derived alkaloids on the gut microbiota of mice with depression-like behaviors. We first established a mouse model of depression via chronic unpredictable mild stress (CUMS) and detected changes in depression-like behaviors and depression-related indicators. Simultaneously, 16S rRNA sequencing was performed to investigate gut microbiota changes. Sophora alopecuroides L.-derived alkaloids improved depression-like behaviors and depression-related indicators in mice. The alkaloids decreased the gut microbiota diversity of CUMS mice and depleted intestinal differentially abundant "harmful" microbiota genera. Spearman analysis showed that there is a certain correlation between the differential microbiota (Lactobacillus, Helicobacter, Oscillospira, Odoribacter, Mucispirillum, Ruminococcus), depression-like behaviors, and depression-related indicators. Combined with the predictive analysis of gut microbiota function, these results indicate that alkaloids improve depression in mice through modulating gut microbiota.

Constitutional 763.3 Kb chromosome 1q43 duplication encompassing only CHRM3 gene identified by next generation sequencing (NGS) in a child with intellectual disability.

BACKGROUND: Deletion or duplication on the distal portion of the long arm of chromosome 1 result in complex and highly variable clinical phenotype including.intellectual disability and autism. CASE PRESENTATION: We report on a patient with intellectual disability and a 763.3 Kb duplication on 1q43 that includes only CHRM3, which was detected by next generation sequencing (NGS). The patient presented with intellectual disability, developmental delay, autistic behavior, limited or no speech, social withdrawal, self-injurious, feeding difficulties, strabismus, short stature, hand anomalie, and no seizures, anxiety, or mood swings, and clinodactyly. CONCLUSIONS: We propose that CHRM3 is the critical gene responsible for the common characteristics in the cases with 1q43 duplication and deletion.

Cortical thickness contributes to cognitive heterogeneity in patients with type 2 diabetes mellitus.

The aim of this study was to investigate cerebral cortical thickness alterations in patients with type 2 diabetes mellitus (T2DM) and their association with mild cognitive impairment (MCI).Thirty T2DM patients without MCI, 30 T2DM patients with MCI, and 30 healthy controls were recruited. All subjects underwent high-resolution sagittal T1-weighted structural imaging using a 3-dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence. The cortical thicknesses of the whole brain of the 3 groups were analyzed and compared using analysis of variance (ANOVA) test. Partial correlations between the cortical thicknesses of each brain region and standard laboratory testing data were analyzed for the T2DM without MCI group. The associations between cortical thicknesses and neuropsychological scale scores were also analyzed in the T2DM with MCI group.Compared with the healthy controls, the T2DM without MCI group showed statistically significant reduction in the cortical thickness of the left posterior cingulate gyrus, right isthmus cingulate gyrus, middle temporal gyrus, paracentral lobule, and transverse temporal gyrus. No significant correlation was found between the standard laboratory testing data and the cortical thicknesses of these cerebral regions. Compared with the T2DM without MCI group, the cortical thickness alterations in the T2DM with MCI group were bidirectional. Increased cortical thickness was found in the left parahippocampal gyrus and the right isthmus cingulate gyrus. Decreased cortical thickness was observed in the left pars triangularis and the right pars opercularis. Significant correlations were found between the cortical thickness of the right pars opercularis and the Complex Figure Test-delayed recall scores (r = 0.464, ρ = 0.015), Trail Making Test A consuming time (r = -0.454, ρ = 0.017), and Montreal Cognitive Assessment scores (r = 0.51, ρ = 0.007).T2DM could influence the gray matter of several brain regions. The cortical thickness reduction of the right pars opercularis may be a biomarker of cognitive impairment and play an important role in its pathophysiological mechanism.

Brain iron deposition in type 2 diabetes mellitus with and without mild cognitive impairment-an in vivo susceptibility mapping study.

This study was performed to investigate iron deposition in the brain of type 2 diabetes mellitus (T2DM) patients using quantitative susceptibility mapping (QSM) and the associated cognitive impairments. Sixty patients diagnosed with T2DM were subjected to neuropsychological tests to determine their cognitive status, and the results were used to subdivide the patients into a T2DM without mild cognitive impairment (MCI) group (n = 30) and a T2DM with MCI group (n = 30). All patients underwent high-resolution susceptibility-weighted imaging, and data processing was performed using SMART (Susceptibility Mapping and Phase Artifacts Removal Toolbox) software. The susceptibility values of the bilateral parietal cortex, frontal white matter, caudate nucleus (CN), putamen (PU), globus pallidus, thalamus, red nucleus, substantia nigra (SN), hippocampus (HP) and dentate nucleus were analyzed and correlated with the neuropsychological cognitive scores. Compared with the normal controls (n = 30), the T2DM without MCI group exhibited significantly increased susceptibility values in the left HP, whereas the T2DM with MCI group showed significantly increased susceptibility values in the bilateral CN, HP, left PU and right SN. Compared with the T2DM without MCI group, the T2DM with MCI group exhibited significantly increased susceptibility values in the right CN, SN and left PU. The susceptibility values for the right CN, SN and left PU were closely correlated with neuropsychological cognitive scores. Our results provide a new relation between T2DM and brain iron deposition and suggested that QSM may be a helpful tool in the detection and evaluation of their cognitive impairment in T2DM.

Direct comparison of PET/CT and MRI to predict the pathological response to neoadjuvant chemotherapy in breast cancer: a meta-analysis.

Both PET/CT and breast MRI are used to assess pathological complete response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. The aim is to compare the utility of PET/CT and breast MRI by using head-to-head comparative studies. Literature databases were searched prior to July 2016. Eleven studies with a total of 527 patients were included. For PET/CT, the pooled SEN was 0.87 (95% confidence interval (CI): 0.71-0.95) and SPE was 0.85 (95% CI: 0.70-0.93). For MRI, the pooled SEN was 0.79 (95% CI: 0.68-0.87) and SPE was 0.82 (95% CI: 0.72-0.89). In the conventional contrast enhanced (CE)-MRI subgroup, PET/CT outperformed conventional CE-MRI with a higher pooled sensitivity (0.88 (95% CI: 0.71, 0.95) vs. 0.74 (95% CI: 0.60, 0.85), P = 0.018). In the early evaluation subgroup, PET/CT was superior to MRI with a notable higher pooled specificity (0.94 (95% CI: 0.78, 0.98) vs. 0.83 (95% CI: 0.81, 0.87), P = 0.015). The diagnostic performance of MRI is similar to that of PET/CT for the assessment of breast cancer response to NAC. However, PET/CT is more sensitive than conventional CE-MRI and more specific if the second imaging scan is performed before 3 cycles of NAC.

[Clinical study of gasless abdominal-wall lifting laparoscopic myomectomy with 5 mm laparoscope].

OBJECTIVE: To explore the feasibility, advantages and clinical value of gasless abdominal-wall lifting laparoscopic myomectomy with 5 mm laparoscope and 2 abdominal holes (1.5-hole-gasless-laparoscopic myomectomy). METHODS: A total of 90 cases of uterine fibroids were randomly divided into 2 groups. Lifting gasless group (n = 46) underwent gasless abdominal-wall lifting laparoscopic myomectomy with 5 mm laparoscope and 2 abdominal holes, and pneumoperitoneum group (n = 44) pneumoperitoneum laparoscopic myomectomy. The operative duration, blood loss volume, average time of single-myoma-removal, intestinal function recovery and hospital stay of both groups were compared. RESULTS: The operative duration, blood loss volume and average time of single-myoma-removal of lifting gasless group were respectively significantly less than those of pneumoperitoneum group (P < 0.01) . The postoperative intestinal function recovery and postoperative hospital stay had no significant difference between two groups (P > 0.05). Three cases of pneumoperitoneum group were converted successfully into myomectomy with traditional 3-hole gasless abdominal wall lifting laparoscopy because of large fibroids in uterine isthmus. A total of 12 newly discovered myomas, not pre-detected ultrasonically, were removed in 10 cases of lifting gasless group. CONCLUSION: 1.5-hole-gasless-laparoscopic myomectomy, like traditional gasless laparoscopy, may avoid the complications of laparoscopic CO2 pneumoperitoneum. The smaller laparoscope-hole and sole operating hole make this maneuver a safe, easy and mini-invasive procedure. It is more suitable for clinical application and popularity in primary care.