A rare presentation of central pontine myelinolysis secondary to hyperglycaemia.

BACKGROUND: Central pontine myelinolysis (CPM) is a rare demyelinating disorder caused by the loss of myelin in the center of the basis pontis. CPM typically occurs with rapid correction of severe chronic hyponatremia and subsequent disturbances in serum osmolality. Although hyperglycaemia is recognized as a pathogenetic factor in serum osmolality fluctuations, CPM is rarely seen in the context of diabetes. CASE PRESENTATION: A 66-year-old Chinese male presented with a history of gait imbalance, mild slurred speech and dysphagia for two weeks. MRI showed the mass lesions in the brainstem, and laboratory examinations showed high blood glucose and HbA1c, as well as increased serum osmolality. The patient was diagnosed with CPM secondary to hyperosmolar hyperglyceamia and received insulin treatment as well as supportive therapy. After six weeks of followup, the patient had fully recovered to a normal state. CONCLUSION: CPM is a potentially fatal neurological condition and can occur in uncontrolled diabetes mellitus. Early diagnosis and timely treatment are crucial for improving the prognosis.

MultiR-Net: A Novel Joint Learning Network for COVID-19 segmentation and classification.

The outbreak of COVID-19 has caused a severe shortage of healthcare resources. Ground Glass Opacity (GGO) and consolidation of chest CT scans have been an essential basis for imaging diagnosis since 2020. The similarity of imaging features between COVID-19 and other pneumonia makes it challenging to distinguish between them and affects radiologists' diagnosis. Recently, deep learning in COVID-19 has been mainly divided into disease classification and lesion segmentation, yet little work has focused on the feature correlation between the two tasks. To address these issues, in this study, we propose MultiR-Net, a 3D deep learning model for combined COVID-19 classification and lesion segmentation, to achieve real-time and interpretable COVID-19 chest CT diagnosis. Precisely, the proposed network consists of two subnets: a multi-scale feature fusion UNet-like subnet for lesion segmentation and a classification subnet for disease diagnosis. The features between the two subnets are fused by the reverse attention mechanism and the iterable training strategy. Meanwhile, we proposed a loss function to enhance the interaction between the two subnets. Individual metrics can not wholly reflect network effectiveness. Thus we quantify the segmentation results with various evaluation metrics such as average surface distance, volume Dice, and test on the dataset. We employ a dataset containing 275 3D CT scans for classifying COVID-19, Community-acquired Pneumonia (CAP), and healthy people and segmented lesions in pneumonia patients. We split the dataset into 70% and 30% for training and testing. Extensive experiments showed that our multi-task model framework obtained an average recall of 93.323%, an average precision of 94.005% on the classification test set, and a 69.95% Volume Dice score on the segmentation test set of our dataset.

Optimization and Developmental Validation of 38-plex InDel Panel for Ancestry Inference.

OBJECTIVES: The previously established 38-plex InDel system was optimized and its performance was validated according to the Scientific Working Group on DNA Analysis Method (SWGDAM) application guidelines. The ancestry inference accuracy of individuals from East Asian, European, African and mixed populations was verified. METHODS: DNA standard sample 9947A was used as the template to establish the optimal amplification conditions by adjusting primer balance, Mg2+ final concentration and optimizing PCR thermal cycle parameters and amplification volume. The allelic dropout, nonspecific amplification and whether the origin of the inferred samples matched the known information were compared to evaluate the performance of this system. RESULTS: The optimal dosage of this system was 0.125-2 ng DNA template. The results of InDel typing were accurate, the amplification equilibrium was good, and the species specificity was good. This system showed certain tolerance to DNA samples including the inhibitor such as hemoglobin (≤80 µmol/L), indigo (≤40 mmol/L), calcium ion (≤1.0 mmol/L), and humic acid (≤90 ng/µL). The system enabled the direct amplification of DNA from saliva and blood on filter paper, and the results of ethnic inference were accurate. The system successfully detected the mixed DNA sample from two individuals. The test results of the system for common biological materials in practical cases were accurate. CONCLUSIONS: The results of the 38-plex InDel system are accurate and reliable, and the performance of the system meets the requirement of the SWGDAM guidelines. This system can accurately differentiate the ancestry origins of individuals from African, European, East Asian, and Eurasian populations and can be implemented in forensic practice.

Annexin A2 degradation contributes to dopaminergic cell apoptosis via regulating p53 in neurodegenerative conditions.

BACKGROUND: P53 overexpression has been shown to involve in mitochondria-mediated dapaminergic neuron cell death in Parkinson's disease. However, the exactly molecular mechanisms responsible for the p53-dependent intrinsic cell death in neurodegenerative conditions remain unclearly. Annexin A2 is a multifunctional protein that negatively regulates p53 expression. The purpose of this study was to explore the mechanism of p53 dependent dopaminergic cell death and implication of Annexin A2 in cellular apoptosis in 1-methyl-4-phenylpyridinium (MPP+)-induced PC12 cells. METHODS: The cell viability of neural PC12 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide assay. Flow cytometry was used to evaluate the apoptosis and mitochondrial transmembrane potential of neural PC12 cells. The expression of p53 and Annexin A2 was analyzed by western blot assay. RESULTS: The present study showed that the exposure of PC12 cells to neurotoxin MPP+ increased the expression levels of p53 and the discharge of mitochondrial transmembrane potential. Notably, Annexin A2 degradation was also observed in this cellular model of Parkinson's disease, in a time and dose-dependent manner. This expressing change of Annexin A2 was in direct proportion to the loss of cell viability of PC12 cells, and this expression pattern was in inverse proportion to p53 levels in this cellular model of Parkinson's disease. CONCLUSION: These results indicated that Annexin A2 degradation plays a crucial role the degeneration of dapaminergic cells of Parkinson's disease, and Annexin A2 downregulation-mediated the cell death is closely associated with mitochondrial dysfunction via p53-dependent pathway; thus provide a novel therapeutic target for Parkinson's disease treatment.

α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions.

Oxidative stress appears to be a central event responsible for the degeneration of dopaminergic neurons in Parkinson's disease (PD). 1-methyl-4­phenyl-1,2,3,6-tetrahydropyridine or its toxic metabolite 1­methyl­4­phenylpyridinium (MPP+) are classical widely­used pharmacological and toxic agents to model PD; they cause the production of reactive oxygen species by inhibiting mitochondrial complex I, leading to DNA oxidative damage and subsequent neuronal death. Previous findings have suggested that proliferating cell nuclear antigen (PCNA), a critical regulatory protein for DNA repair, is involved in dopaminergic neuron damage in the MPP+­induced PD model. The naturally occurring dithiol compound, α­lipoic acid (ALA) has been reported to provide neuroprotection in in vitro models of PD. The molecular mechanism by which ALA reduces neuronal death in PD remains to be fully elucidated. The present study aimed to analyze the ability of ALA to protect neuronal PC12 cells from the toxicity induced by MPP+, and the molecular mechanism underlying these actions using MTT and lactate dehydrogenase cytotoxicity assays, Hoechst 33258 staining and western blot analysis. The results demonstrated that ALA efficiently increased the production of PCNA in MPP+­treated PC12 cells. Accordingly, ALA treatment attenuated MPP+­induced toxicity in the PC12 cells, and reduced cell apoptosis. The increase in the expression levels of PCNA by ALA in the MPP+­treated PC12 cells appeared to be mediated by repression of the p53 protein, as the expression of p53 was increased by MPP+­treatment and reduced by ALA. Taken together, these results indicated that ALA protected dopaminergic neurons against MPP+­induced neurotoxicity through its ability to upregulate the DNA repair protein, PCNA, via the P53 pathway.

The changes in the levels of IL-6, IL-17, and IL-21 in the acute stage of childhood asthma.

BACKGROUND: Asthma is the most common disease in children, and its pathogenesis is highly complicated. METHODS: CD4+ cells and CD4+ IL-17+ cells were analysed by flow cytometry, and the ratio of CD4+ cells to the peripheral blood mononuclear cells (PBMCs) and CD4+ IL-17+ cells to PMBCs were calculated from the control group, acute group, and moderate group. The levels of protein expression of IL-6, IL-17, and IL-21 were detected by ELISA in the plasma and culture supernatants of PBMCs of the three groups. The correlations between IL-7 and IL-6, IL-7 and IL-21 were analysed in culture supernatants of PBMCs of the three groups. RESULTS: The mean ratio of CD4+ IL-17+ cells/peripheral blood mononuclear cells (PBMCs) was 4.32% in the acute group, which was higher than in the control group and moderate group. The levels of IL-6 and IL-17 were elevated, and the levels of IL-21 were decreased in the acute group. The levels of IL-17 and IL-6 were positively correlated (r = 0.182, p = 0.03), and the levels of IL-17 and IL-21 were negatively correlated (r = -0.834, p = 0.02). CONCLUSIONS: The results suggest that the levels of IL-17 and IL-6 are related to the severity of asthma. Furthermore, IL-17 may play a role in the development of childhood asthma.

Fenestrations accompanied by intracranial aneurysms assessed with magnetic resonance angiography.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the anatomical changes and investigate the prevalence in intracranial aneurysm with fenestrations using magnetic resonance angiography (MRA). MATERIALS AND METHODS: Between June 2008 and October 2010, 4652 patients (aged 23-73 years) with suspected intracranial aneurysm or other cerebrovascular diseases underwent MRA examination. MRA was performed using a three-dimensional time-of-flight technique (3D-TOF) with volume rendering (VR) and maximum intensity projection reconstruction methods. The presence and location of fenestrations and aneurysms was reviewed. When fenestrations were present in combination with aneurysms, we noted the relationship of the locations. The classification of fenestration accompanied by intracranial aneurysm was divided into three types according to the anatomical relationship as follows: Type I, aneurysm adjacent to but not on a fenestration; Type II, aneurysm located on the fenestration; type III, aneurysm located at a position remote from a fenestration. RESULTS: Among the 4652 patients examined, 409 patients were defined with 412 intracranial aneurysms, and the prevalence of aneurysms was 8.8%. One hundred and forty-one patients were identified with fenestrations; 24 of these patients were confirmed with intracranial aneurysms. Seven cases were classified as type I, three as type II and 14 as type III. The prevalence of intracranial aneurysm with fenestrations was 17.0%, with significant statistical difference compared with aneurysms unaccompanied with fenestrations (P=0.0064). CONCLUSION: The anatomical relationship between fenestrations and intracranial aneurysms was visualized by MRA with VR, which displayed pathologies with sufficient clarity to enable diagnosis. Furthermore, the results of this study suggest that physicians should be alerted to the occurrence of intracranial aneurysm following the detection of fenestrations by MRA.

[Effects of cocaine on activities of ATPase, LDH and SDH in mouse splenocytes].

OBJECTIVE: To examine the effects of cocaine on the activities of ATPase, LDH and SDH in cultured mouse splenocytes in vitro. METHODS: The ATPase, LDH and SDH activities in mouse splenocytes were detected at day 7 after continuous culturing the mouse cells exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL in vitro. RESULTS: The activities of ATPase, LDH and SDH in mouse splenocytes exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL were significantly decreased after continuous culturing for 7 days. CONCLUSION: The present study demonstrated that cocaine could inhibit the activities of ATPase, LDH and SDH in cultured splenocytes in vitro.

Bovine caveolin-2 cloning and effects of shear stress on its localization in bovine aortic endothelial cells.

Caveolae are plasmalemmal domains enriched with cholesterol, caveolins, and signaling molecules. Normally, cells that express caveolin-1 also express caveolin-2, but this has not been demonstrated in bovine aortic endothelial cells (BAECs). Here, we show that BAECs express caveolin-2, which localizes in caveolae with caveolin-1. We have cloned the bovine caveolin-2 gene and after comparison with known protein sequences (human, murine, rat, and canine) have found divergent immunogenic regions (amino acid [aa] 21 to aa 50 and aa 79 to 88), which may explain the inability to detect caveolin-2 in different cell types. We developed a bovine caveolin-2-specific antibody to examine this protein's expression and localization in BAECs. We used differential gradient centrifugations and immunoprecipitation to show that bovine caveolin-2 and caveolin-1 form a hetero-oligomer in plasma membrane caveolae. Using immunocytochemistry we show that a pool of caveolin-2 also colocalizes with the cis-Golgi in static culture, but unlike caveolin-1, this Golgi associated pool is maintained after 1 day of shear exposure. Therefore, the interaction of caveolin-2 with caveolin-1 could play an important role in caveolae biogenesis and shear stimulated mechano-signal transduction.