ABSTRACT
Abnormal synchronous neuronal activity has been widely detected by brain imaging of autistic patients, but its underlying neural mechanism remains unclear. Compared with wild-type mice, our in vivo two-photon imaging showed that transgenic (Tg1) mice over-expressing human autism risk gene MeCP2 exhibited higher neuronal synchrony in the young but lower synchrony in the adult stage. Whole-cell recording of neuronal pairs in brain slices revealed that higher neuronal synchrony in young postnatal Tg1 mice was attributed mainly to more prevalent giant slow inward currents (SICs). Both in vivo and slice imaging further demonstrated more dynamic activity and higher synchrony in astrocytes from young Tg1 mice. Blocking astrocytic gap junctions markedly decreased the generation of SICs and overall cell synchrony in the Tg1 brain. Furthermore, the expression level of Cx43 protein and the coupling efficiency of astrocyte gap junctions remained unchanged in Tg1 mice. Thus, astrocytic gap junctions facilitate but do not act as a direct trigger for the abnormal neuronal synchrony in young Tg1 mice, revealing the potential role of the astrocyte network in the pathogenesis of MeCP2 duplication syndrome.
ABSTRACT
Methyl-CpG binding protein 2 (MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing. Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, heightened anxiety, epilepsy, autistic phenotypes, and early death. Reversal of the abnormal phenotypes in adult mice with MECP2 duplication (MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated. However, whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown. Here, we found that MECP2-TG mice showed a significant social recognition deficit, and were prone to display aversive-like behaviors, including heightened anxiety-like behaviors and a fear generalization phenotype. In addition, reduced locomotor activity was observed in MECP2-TG mice. However, appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice. Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors. We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex (mPFC) and bed nuclei of the stria terminalis (BST) of adult MECP2-TG mice, and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit. These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice, and provide new insight into potential therapies for MECP2 duplication syndrome.
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Objective To investigate the changes of brain CT imaging in patients with cerebral cysticercosis during the period of anti-cysticercus chemotherapy. Methods A total of 380 inpatients that were conformed to the practical diagnostic criteria of cerebral cysticercosis were enrolled in this study in the Third Affiliated Hospital of Shandong Academy of Medical Sciences from May 2010 to May 2015. All the patients were given anti-cysticercus chemotherapy (albendazole and praziquantel). All the patients received brain CT scan, and of which 210 received enhanced scan. The data of CT imaging were systematically reviewed. Results Before the treatment, the CT images of the patients showed single or multiple small cystic (s) with low density and small nodule-like cephalomere with high density. The re-examinations of CT showed that there were 81.58% (310/380) of the patients whose low density foci were completely absorbed, there were 16.32% (62/380) of the patients whose foci were mostly absorbed, and there were 2.11% (8/380) of the patients whose foci were calcified. Along with the prolongation of treatment time, the side effects were gradually reduced, and in the third course of treatment, the foci were absorbed or calcified in most of the patients. Conclusion CT examination can diagnose the lesion site, range and classification of cerebral cysticercosis, and can evaluate the effect of the therapy according to the changes of CT imaging during the period of anti-cysticercus chemotherapy.
ABSTRACT
Objective To investigate the changes of brain CT imaging in patients with cerebral cysticercosis during the period of anti-cysticercus chemotherapy. Methods A total of 380 inpatients that were conformed to the practical diagnostic criteria of cerebral cysticercosis were enrolled in this study in the Third Affiliated Hospital of Shandong Academy of Medical Sciences from May 2010 to May 2015. All the patients were given anti-cysticercus chemotherapy (albendazole and praziquantel). All the patients received brain CT scan, and of which 210 received enhanced scan. The data of CT imaging were systematically reviewed. Results Before the treatment, the CT images of the patients showed single or multiple small cystic (s) with low density and small nodule-like cephalomere with high density. The re-examinations of CT showed that there were 81.58% (310/380) of the patients whose low density foci were completely absorbed, there were 16.32% (62/380) of the patients whose foci were mostly absorbed, and there were 2.11% (8/380) of the patients whose foci were calcified. Along with the prolongation of treatment time, the side effects were gradually reduced, and in the third course of treatment, the foci were absorbed or calcified in most of the patients. Conclusion CT examination can diagnose the lesion site, range and classification of cerebral cysticercosis, and can evaluate the effect of the therapy according to the changes of CT imaging during the period of anti-cysticercus chemotherapy.
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Objective: To observe the short- and long-term clinical outcomes of fraction flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients with SYNTAX score≥33 unsuitable for coronary artery bypass grafting (CABG). Methods: A total of 117 CAD patients admitted in our hospital from 2012-01 to 2015-06 were enrolled. Since SYNTAX score≥33, EuroSCORE>6, the patients were unsuitable for CABG and treated in 2 groups: Medication group, n=20 and PCI group, during FFR-guided PCI procedure, patients received ROTA or IVUS according to physician's experience, n=97. All patients were followed-up for at least 12 months. Meanwhile, taking "coronary stent and bypass", "CABG and PCI" as key words, we searched relevant documents in VIP Chinese science and technology journal full-text database, WanFang medical database, ChinaNet and Chinese biomedical literature database from 2012-01-01 to 2015-12-31, patients' outcomes were compared with the above references to explore the clinical benefit. Results: ① PCI group and Medication group had similar SYNTAX score and EuroSCORE, P>0.05. The common pathogenesis was LAD involvement, chronic occlusion was 31.3% (5/16) in patients with partial revascularization.②PCI group had 18.6% (18/97) incidence of major adverse cardiac and cerebral events (MACCE), 2 patients died during follow-up period and 9 received revascularization; Medication group had 60% (12/20) incidence of MACCE, 3 patients died during follow-up period; the difference between 2 groups showed statistical meaning, P<0.05.③There were 22 relevant documents retrieved as comparison; in our research, PCI group had similar incidence of MACCE to the documents, P>0.05; Medication group had increased incidence of MACCE than the documents, P<0.05. Conclusion: FFR-guided PCI could bring clinical benefit in CAD patients with SYNTAX score≥33 unsuitable for CABG.
ABSTRACT
<p><b>BACKGROUND</b>Tricuspid regurgitation (TR) is frequently associated with severe mitral stenosis (MS), the importance of significant TR was often neglected. However, TR influences the outcome of patients. The aim of this study was to investigate the efficacy and safety of percutaneous balloon mitral valvuloplasty (PBMV) procedure in rheumatic heart disease patients with mitral valve (MV) stenosis and tricuspid valve regurgitation.</p><p><b>METHODS</b>Two hundred and twenty patients were enrolled in this study due to rheumatic heart disease with MS combined with TR. Mitral balloon catheter made in China was used to expand MV. The following parameters were measured before and after PBMV: MV area (MVA), TR area (TRA), atrial pressure and diameter, and pulmonary artery pressure (PAP). The patients were followed for 6 months to 9 years.</p><p><b>RESULTS</b>After PBMV, the MVAs increased significantly (1.7 ± 0.3 cm 2 vs. 0.9 ± 0.3 cm 2 , P < 0.01); TRA significantly decreased (6.3 ± 1.7 cm 2 vs. 14.2 ± 6.5 cm 2 , P < 0.01), right atrial area (RAA) decreased significantly (21.5 ± 4.5 cm 2 vs. 25.4 ± 4.3 cm 2 , P < 0.05), TRA/RAA (%) decreased significantly (29.3 ± 3.2% vs. 44.2 ± 3.6%, P < 0.01). TR velocity (TRV) and TR continue time (TRT) as well as TRV × TRT decreased significantly (183.4 ± 9.4 cm/s vs. 254.5 ± 10.7 cm/s, P < 0.01; 185.7 ± 13.6 ms vs. 238.6 ± 11.3 ms, P < 0.01; 34.2 ± 5.6 cm vs. 60.7 ± 8.5 cm, P < 0.01, respectively). The postoperative left atrial diameter (LAD) significantly reduced (41.3 ± 6.2 mm vs. 49.8 ± 6.8 mm, P < 0.01) and the postoperative right atrial diameter (RAD) significantly reduced (28.7 ± 5.6 mm vs. 46.5 ± 6.3 mm, P < 0.01); the postoperative left atrium pressure significantly reduced (15.6 ± 6.1 mmHg vs. 26.5 ± 6.6 mmHg, P < 0.01), the postoperative right atrial pressure decreased significantly (13.2 ± 2.4 mmHg vs. 18.5 ± 4.3 mmHg, P < 0.01). The pulmonary arterial pressure decreased significantly after PBMV (48.2 ± 10.3 mmHg vs. 60.6 ± 15.5 mmHg, P < 0.01). The symptom of chest tightness and short of breath obviously alleviated. All cases followed-up for 6 months to 9 years (average 75 ± 32 months), 2 patients with severe regurgitation died (1 case of massive cerebral infarction, and 1 case of heart failure after 6 years and 8 years, respectively), 2 cases lost access. At the end of follow-up, MVA has been reduced compared with the postoperative (1.4 ± 0.4 cm 2 vs. 1.7 ± 0.3 cm 2 , P < 0.05); LAD slightly increased compared with the postoperative (45.2 ± 5.7 mm vs. 41.4 ± 6.3 mm, P < 0.05), RAD slightly also increased compared with the postoperative (36.1 ± 6.3 mm vs. 28.6 ± 5.5 mm, P < 0.05), but did not recover to the preoperative level. TRA slightly increased compared with the postoperative, but the difference was not statistically significant (P > 0.05). The PAP and left ventricular ejection fraction appeared no statistical difference compared with the postoperative (P > 0.05), the remaining patients without serious complications.</p><p><b>CONCLUSIONS</b>PBMV is a safe and effective procedure for MS combined with TR in patients of rheumatic heart disease. It can alleviate the symptoms and reduce the size of TR. It can also improve the quality-of-life and prognosis. Its recent and mid-term efficacy is certain. While its long-term efficacy remains to be observed.</p>