Altered static and dynamic functional connectivity of the default mode network across epilepsy subtypes in children: A resting-state fMRI study.

BACKGROUND: Epilepsy is a chronic neurologic disorder characterized by abnormal functioning of brain networks, making it a complex research topic. Recent advancements in neuroimaging technology offer an effective approach to unraveling the intricacies of the human brain. Within different types of epilepsy, there is growing recognition regarding ongoing changes in the default mode network (DMN). However, little is known about the shared and distinct alterations of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in DMN among epileptic subtypes, especially in children with epilepsy. METHODS: Here, 110 children with epilepsy at a single center, including idiopathic generalized epilepsy (IGE), frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE), and parietal lobe epilepsy (PLE), as well as 84 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (fMRI) scan. We investigated both sFC and dFC between groups of the DMN. RESULTS: Decreased static and dynamic connectivity within the DMN subsystem were shared by all subtypes. In each epilepsy subtype, children with epilepsy displayed significant and distinct patterns of DMN connectivity compared to the control group: the IGE group showed reduced interhemispheric connectivity, the FLE group consistently demonstrated disturbances in frontal region connectivity, the TLE group exhibited significant disruptions in hippocampal connectivity, and the PLE group displayed a notable decrease in parietal-temporal connectivity within the DMN. Some state-specific FC disruptions (decreased dFC) were observed in each epilepsy subtype that cannot detect by sFC. To determine their uniqueness within specific subtypes, bootstrapping methods were employed and found the significant results (IGE: between PCC and bilateral precuneus, FLE: between right middle frontal gyrus and bilateral middle temporal gyrus, TLE: between left Hippocampus and right fusiform, PLE: between left angular and cingulate cortex). Furthermore, only children with IGE exhibited dynamic features associated with clinical variables. CONCLUSIONS: Our findings highlight both shared and distinct FC alterations within the DMN in children with different types of epilepsy. Furthermore, our work provides a novel perspective on the functional alterations in the DMN of pediatric patients, suggesting that combined sFC and dFC analysis can provide valuable insights for deepening our understanding of the neuronal mechanism underlying epilepsy in children.

Abnormal static and dynamic functional network connectivity of the whole-brain in children with generalized tonic-clonic seizures.

Introduction: Generalized tonic-clonic seizures (GTCS) are a subtype of generalized seizures exhibiting bursts of bilaterally synchronous generalized spike-wave discharges. Numerous neuroimaging studies have reported aberrant functional activity and topological organization of brain network in epilepsy patients with GTCS, but most studies have focused on adults. However, the effect of GTCS on the spatial and temporal properties of brain function in children remains unclear. The present study aimed to explore whole-brain static (sFC) and dynamic functional connectivity (dFC) in children with GTCS. Methods: Twenty-three children with GTCS and 32 matched healthy controls (HCs) were recruited for the present study. Resting-state functional magnetic resonance imaging (MRI) data were collected for each subject. The group independent component analysis method was used to obtain independent components (ICs). Then, sFC and dFC methods were applied and the differences in functional connectivity (FC) were compared between the children with GTCS and the HCs. Additionally, we investigated the correlations between the dFC indicators and epilepsy duration. Results: Compared to HCs, GTCS patients exhibited a significant decrease in sFC strengths among most networks. The K-means clustering method was implemented for dFC analysis, and the optimal number of clusters was estimated: two discrete connectivity configurations, State 1 (strong connection) and State 2 (weak connection). The decreased dFC mainly occurred in State 1, especially the dFC between the visual network (VIS) and somatomotor network (SMN); but the increased dFC mainly occurred in State 2 among most networks in GTCS children. In addition, GTCS children showed significantly shorter mean dwell time and lower fractional windows in stronger connected State 1, while GTCS children showed significantly longer mean dwell time in weaker connected State 2. In addition, the dFC properties, including mean dwell time and fractional windows, were significantly correlated with epilepsy duration. Conclusion: Our results indicated that GTCS epilepsy not only alters the connectivity strength but also changes the temporal properties of connectivity in networks in the whole brain. These findings also emphasized the differences in sFC and dFC in children with GTCS. Combining sFC and dFC methods may provide more comprehensive understanding of the abnormal changes in brain architecture in children with GTCS.

Pharmacogenomics of oxcarbazepine in the treatment of epilepsy.

Oxcarbazepine (OXC) is one of the preferred drugs for partial seizures and generalized tonic-clonic seizures. However, clinical studies have found that there are considerable differences among different populations in OXC therapeutic efficacy or safety that result from the function changes of metabolic enzymes, transporters and other receptors involved in pharmacokinetics and pharmacodynamics in vivo. The authors collected all the information on the clinically reported associations between variants of common genes (e.g., UGT1A9, HLA-B, ABCB1) and OXC. In conclusion, these associations based on variants are beneficial for adjusting the medication regimen, which could be useful for individualized treatment with OXC.

As a new-generation aromatic antiepileptic drug, oxcarbazepine (OXC) is often used for epilepsy treatment. It is known that when OXC is absorbed, it is reduced to an active metabolite in the liver and enters the brain through the blood circulation to play an antiepileptic role. Therefore, the variations of proteins participating in the process, including drug metabolic enzymes, transporters, drug targets and other receptors, have an effect on the efficacy and safety of OXC in vivo. In this study, the associations of some variants of common genes with OXC are summarized to provide epileptic patients an appropriate dose of OXC or reduce the risk of OXC-induced toxicity, which are in favor of personalized OXC treatment for patients with epilepsy.

[Retracted] MicroRNA­326 inhibits cell proliferation and invasion, activating apoptosis in hepatocellular carcinoma by directly targeting LIM and SH3 protein 1.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that various panels showing data from flow cytometric experiments in Figs. 2E, 5E and 6E, and the cell migration and invasion assay data shown in Fig. 2D and 6D, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere when it was submitted to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 1569­1578, 2017; DOI: 10.3892/or.2017.5810].

Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

Purpose@#Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. @*Materials and Methods@#The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. @*Results@#We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. @*Conclusion@#The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Multiomics Study Reveals Enterococcus and Subdoligranulum Are Beneficial to Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a life-threatening disease for premature infants with low body weight. Due to its fragile gut microbiome and successful treatment of fecal microbiota transplantation (FMT) for intestinal disease, we aimed to reveal the multiple-omics changes after FMT and/or sulperazone treatment. In this study, 2-week-old newborn rabbits were used to simulate the NEC model and grouped into healthy control, NEC, sulperazone treatment, FTM treatment, and FMT and sulperazone combination treatment. We evaluated the intestinal pathology and survival to define the benefit from each treatment and performed microbiome and transcriptome analysis to reveal the changes in microcosmic level, which could be helpful to understand the pathogenesis of NEC and develop new strategy. We found NEC rabbits benefit more from the combination of FMT and sulperazone treatment. Combination treatment reverses a lot of microorganisms dysregulated by NEC and showed the most similar transcript profiler with healthy control. Moreover, a combination of FMT and sulperazone significantly prolonged the survival of NEC rabbits. Function enrichment showed that metabolism and viral life cycle are the most significant changes in NEC. FMT is a common therapy method for NEC. Meanwhile, in the severe situation of NEC with intestinal infection, the first therapy strategy is preferred the third-generation cephalosporin, among which sulperazone is used widely and the effect is remarkable. So, we used sulperazone to treat the rabbits with the NEC. In this research, we aim to explore the different effects on NEC between FMT and sulperazone as well as the combination. Considering the microbiome and transcriptome result, we make a conclusion that the Enterococcus and Subdoligranulum benefits NEC by influencing the bacterial phages and butyrate production, respectively.

Nek2B accelerates the progression of hepatocellular carcinoma through regulating SFRP1 to activate the Wnt/ß-catenin pathway.

PURPOSE: The purpose of this study was to clarify the expression pattern of Nek2B in hepatocellular carcinoma (HCC) and its influence on malignant phenotypes of HCC through regulating SFRP1 and the Wnt/ß-catenin pathway. METHODS: Nek2B levels in 64 paired HCC tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between Nek2B level and clinical parameters of HCC patients was analyzed. Regulatory effects of Nek2B and SFRP1 on clonality, proliferation and apoptosis of MHCC97H and Hep3B cells were determined through functional experiments. Western blot was conducted to detect protein levels of SFRP1, ß-catenin, c-myc, cyclinD1 and MMP7 in HCC cells with overexpression or knockdown of Nek2B. At last, rescue experiments were performed to clarify the role of Nek2B/SFRP1 regulatory loop in aggravating the progression of HCC. RESULTS: Nek2B was upregulated in HCC tissues and cells. HCC patients expressing a high level of Nek2B were in more advanced tumor stage and had worse prognosis. Overexpression of Nek2B in MHCC97H cells enhanced clonality, 5-Ethynyl-2'- deoxyuridine (EdU)-positive ratio and suppressed apoptosis. Besides, knockdown of Nek2B in Hep3B cells yielded the opposite results. SFRP1 was downregulated in HCC, and low level of SFRP1 predicted worse prognosis of HCC. Overexpression of Nek2B downregulated SFRP1, but upregulated ß-catenin, c-myc, cyclinD1 and MMP7 in HCC cells. Importantly, Nek2B/SFRP1 regulatory loop was identified to aggravate the progression of HCC. CONCLUSIONS: Nek2B is upregulated in HCC, and closely linked to tumor stage and poor prognosis in HCC patients. Through interaction with SFRP1, Nek2B aggravates the progression of HCC by activating the Wnt/ß-catenin pathway.

A non-invasive model for predicting liver fibrosis in HBeAg-positive patients with normal or slightly elevated alanine aminotransferase.

ABSTRACT: Early and accurate diagnosis of liver fibrosis is necessary for HBeAg-positive chronic hepatitis B (CHB) patients with normal or slightly increased alanine aminotransferase (ALT), Liver biopsy and many non-invasive predicting markers have several application restrictions in grass-roots hospitals. We aimed to construct a non-invasive model based on routinely serum markers to predict liver fibrosis for this population.A total of 363 CHB patients with HBeAg-positive, ALT ≤2-fold the upper limit of normal and liver biopsy data were randomly divided into training (n = 266) and validation groups (n = 97). Two non-invasive models were established based on multivariable logistic regression analysis in the training group. Model 2 with a lower Akaike information criterion (AIC) was selected as a better predictive model. Receiver operating characteristic (ROC) was used to evaluate the model and was then independently validated in the validation group.The formula of Model 2 was logit (Model value) = 5.67+0.08 × Age -2.44 × log10 [the quantification of serum HBsAg (qHBsAg)] -0.60 × log10 [the quantification of serum HBeAg (qHBeAg)]+0.02 × ALT+0.03 ×  aspartate aminotransferase (AST). The area under the ROC curve (AUC) was 0.89 for the training group and 0.86 for the validation group. Using 2 cut-off points of -2.61 and 0.25, 59% of patients could be identified with liver fibrosis and antiviral treatment decisions were made without liver biopsies, and 149 patients were recommended to undergo liver biopsy for accurate diagnosis.In this study, the non-invasive model could predict liver fibrosis and may reduce the need for liver biopsy in HBeAg-positive CHB patients with normal or slightly increased ALT.

Neutrophil-to-lymphocyte ratio predicts prognosis of patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is one predictive factor for poor prognosis of patients with hepatocellular carcinoma (HCC). In response to contradictory data concerning the predictive ability of NLR, we performed a meta-analysis for the determination of its prognostic value in patients with HCC. METHODS: We systematically searched several databases including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang databases with the updated date of September 21, 2020. Inclusion criteria: RCT studies reporting the prognostic value of the serum levels of NLR in HCC patients receiving treatment were enrolled. Pooled estimates of odds ratio (OR) and diagnostic odds ratio (DOR) were used to assess the prognostic performance of NLR in HCC patients. Overall survival (OS) was the primary outcome and progression-free survival (PFS) was secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Furthermore, risk of bias assessment of included studies is specified by Cochrane Risk Bias Assessment Tool. RESULTS: This analysis included 9 studies containing a total of 3,862 HCC patients. High baseline NLR was significantly correlated with poor prognosis or recurrence. The patient-based analysis of pooled estimates was as follows: sensitivity, 0.68 (95% CI: 0.58-0.77); specificity, 0.73 (95% CI: 0.61-0.82); DOR, 6.347 (95% CI: 5.450-7.391). The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were 2.5 (95% CI: 1.8-3.6) and 0.43 (95% CI: 0.33-0.57). Furthermore, the area under the curve (AUC) of summary receiver operating characteristic (SROC) reflecting the prognostic accuracy was 0.76 (95% CI: 0.72-0.80). Results obtained from subgroup meta-analyses and overall meta-analyses were accordingly consistent with each other. CONCLUSIONS: Our findings suggested that NLR is an effective prognostic factor for patients with HCC, especially for those from East Asian populations with high incidence. In the future, trials with larger sample sizes and more high-quality evidence are needed to further improve patient outcomes.

Gene Mining and Sequence Analysis of Purine Nucleosidase Based on RNA-Seq.

Caterpillar fungus (Ophiocordyceps sinensis) is one of the most valued fungal Traditional Chinese medicine (TCM), and it contains plenty of active ingredients such as adenosine. Adenosine is considered as a biologically effective ingredient that has a variety of anti-tumor and immunomodulatory activities. In order to further elucidate the mechanism of purine nucleosidase (PN) in adenosine biosynthesis, a gene encoding PN was successfully mined and further analyzed based on the RNA-Seq database of caterpillar fungus. The full-length cDNA of PN was 855 bp, which encoded 284 amino acids. BLAST analysis showed the highest homology of 85.06% with nucleoside hydrolase in NCBI. ProtProm analysis showed that the relative molecular weight was 30.69 kDa and the isoelectric point was 11.55. The secondary structure of PN was predicted by Predict Protein; the results showed that alpha helix structure accounted for 28.17%, strand structure accounted for 11.97%, and loop structure accounted for 59.86%. Moreover, PN gene was further cloned from transcriptome and detected by agarose gel electrophoresis for verification. This study provides more sufficient scientific basis and new ideas for the genetic regulation of adenosine biosynthesis in fungal TCM.

Circulating S100A8/A9 Levels Reflect Intraocular Inflammation in Uveitis Patients.

Purpose: To investigate whether there is an association between circulating S100A8/A9 levels and uveitis activity.Methods: A total of 549 plasma samples were collected from uveitis patients and non-uveitic controls.Results: S100A8/A9 plasma levels were elevated in uveitis patients compared to non-uveitic controls (P < 0.001). S100A8/A9 plasma levels in patients with active acute anterior uveitis (AAU) were significantly elevated and remarkably decreased in parallel with the severity of intraocular inflammation after corticosteroid treatment (P < 0.001). S100A8/A9 plasma levels were also higher in AAU patients with ankylosing spondylitis (AS) than in patients without AS (P = 0.02). S100A8/A9 plasma levels were significantly increased in uveitis patients with elevated C-reactive protein (CRP, P = 0.004) or erythrocyte sedimentation rates (ESR, P = 0.049) levels compared to uveitis patients with normal CRP or ESR values.Conclusion: Circulating S100A8/A9 might be a useful biomarker for the measurement of intraocular inflammation.

Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration.

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases.

Related Research and Recent Progress of Ischemic Penumbra.

We reviewed recent studies on ischemic penumbra, including the evolution of the definitions of ischemic penumbra and observations on the characteristics of blood flow and the molecular evolutionary mechanism of ischemic tissues; at the same time, a brief summary of current clinical treatment methods were included. From the perspective of neuroimaging and clinical treatment, the characteristics of cerebral blood flow, oxygen consumption, cell water content, and metabolites were analyzed, to evaluate the diagnosis and evolution of ischemic penumbra. The analysis of the evolutionary characteristics of multiple gene molecules and metabolites may provide ideas for clinical imaging diagnosis and clinical treatment, also allow the combination of multiparameter imaging indexes to be more accurate and effective for the assessment of ischemic penumbra. The research hotspot of imaging on the ischemic penumbra region in the future may be more focused on reflecting the evolutionary characteristics of local metabolites in the ischemic area. Using multimodality imaging to evaluate IP zones and guide the formulation of clinical treatment protocols.

Characterization of steryl glycosides in marine microalgae by gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS).

BACKGROUND: Steryl glycosides (SGs) are sterol conjugates found in various plants, especially in those making up human diets. It has been demonstrated that SGs have potential health benefits, and they could be used as food supplements in a variety of food matrixes. Marine microalgae are a potential resource for human food and ingredients. In this study, gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS) was used to characterize unknown SGs in eight microalgae belonging to different classes (Isochrysis galbana 3011, Pavlova viridis, Platymonas helgolandica, Conticribra weissflogii, Thalassiosira pseudonana, Nitzschia closterium, Gymnodinium sp., and Karlodinum veneficum). RESULTS: The SGs were first extracted from lyophilized algae with chloroform-methanol, purified by solid-phase extraction and analyzed as trimethylsilyl derivatives. Nine SGs have been identified. In particular, new SGs like occelasteryl glycoside and stellasteryl glycoside were found in Gymnodinium sp., 24-methylene cholesteryl glycoside was detected in P. helgolandica, and 4,24-dimethylcholestan-3-yl glycoside was identified as the main constituent of microalga K. veneficum. The results also showed that the compositions of SGs in different microalgae varied, with a range of 5.234 to 0.036 g kg-1 , and microalga P. viridis contained the most abundant SGs. CONCLUSION: GC-QQQ-MS is a powerful tool to detect SGs with different structures from a variety of microalgae. The compositions of SGs in different microalgae varied greatly. Microalgae are a good source of highly valued SGs. © 2017 Society of Chemical Industry.

Antibacterial Effect of 2R,3R-dihydromyricetin on the Cellular Functions of Staphylococcus aureus.

The C-3-OH, C-4 carbonyl oxygen and hydrogenation of C2=C3 bond on the C-ring of 2R,3R-dihydromyricetin (DMY) proved to be not necessary for the antibacterial activity against Staphylococcus aureus. DMY significantly decreased the intracellular ATP of S. aureus cells but had few effects on pHin, proline oxidation, succinate dehydrogenase activity or malate dehydrogenase activity.

Marker Pen Device with Concentration Gradient Nib for Antibiotic Susceptibility Testing

BACKGROUND: Pen-based devices have emerged as useful tools for measuring pH and glucose, and for fabricating microchannels and microarrays. Pen-based devices take advantage of flexible patterning, inexpensive costs, and small volumes, thereby saving time and increasing efficiency. We have developed a gradient nib marker pen device that generated simultaneously different antibiotic concentrations in bacteria antibiotic susceptibility testing (AST). METHODS: The device can deposit on the target surface with the antibiotic gradient. The designed polyester fiber nibs are a highly uniform porosity with unidirectional orientation and produce a visible gradient pattern. RESULTS: We have demonstrated and quantitatively analyzed bacterial growth after antibiotic marking. The antibiotic marking produces an inhibition zone of bacterial growth. The inhibition zones of bacterial growth are captured and converted to 8-bit grayscale images, and then quantified by gray values using the Image J program. A profile of the inhibition zone showed different gray values in response to bacterial viability. CONCLUSION: The gradient nib marker pen device can be used to determine the quantitative antibiotic concentration based on the relationship between gray values and bacterial density conveniently without requiring a series of dilution tubes, including nutrient medium, and diversely diluted antibiotics.

Expression of RGMb in brain tissue of MCAO rats and its relationship with axonal regeneration.

OBJECTIVE: To investigate the changes in the expression of repulsive guidance molecule b (RGMb) in brain tissue of rats with ischemic cerebral infarction and determine its relationship with axonal regeneration, synapse remodeling and magnetic resonance imaging (MRI) parameters with magnetic resonance diffusion tensor imaging as the dynamic continuous monitoring method in vivo, so as to explore the pathophysiological mechanism of the occurrence, development and prognosis of cerebral infarction. METHODS: Ninety Sprague-Dawley (SD) rats were randomly divided into six groups, namely control group, middle cerebral artery occlusion (MCAO) 12-h group, MCAO 24-h group, MCAO 48-h group, MCAO 7-day group and MCAO 10-day group, each of 15 animals. Rats were examined by head MRI at corresponding time points, followed by measurement of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values. Subsequently, brain tissues were taken to detect the expression of RGMb, axonal regeneration and synapse remodeling. RESULTS: After infarction, ADC and FA values of the infarcted core area were lower in rats of each group compared to those in rats of normal group (P<0.05), which was lowest at 12h. The positive expressions of RGMb and synaptophysin were continuously increased from the 12th hour after operation, which reached a peak at 48h; while axonas was gradually reduced after operation in each group, which revealed the most obvious damage in the MCAO 24-h group. The protein expression of RGMb was negatively correlated with MRI parameters and axon growth. CONCLUSION: After supratentorial cerebral infarction, the expressions of RGMb and synaptophysin were up-regulated in rats, neurofilament protein (NF-200) expression was decreased, and MRI parameters (ADC and FA values) were reduced, indicating that RGMb protein may be involved in the regeneration and remodeling of axons and synapses, and exert an important role in pathophysiological processes such as nerve regeneration disturbance and neuron apoptosis after cerebral ischemia injury. In vivo MRI can be a noninvasive technique to monitor the areas of cerebral infarction and the recovery of neurological function.

Perfusion-weighted magnetic resonance imaging in the assessment of haemodynamics following stent angioplasty in patients with symptomatic middle cerebral artery plaque stenosis at the M1 segment.

The most effective strategy to assess changes in the brain haemodynamics of stent angioplasty in patients with symptomatic ischemia of the M1 segment of the middle cerebral artery (MCA) remains unknown. The purpose of the present study was to use perfusion-weighted magnetic resonance imaging (PWI) to evaluate the effect of stent angioplasty in treating patients with symptomatic MCA plaque stenosis. Stent angioplasty was performed on 23 patients with reduplicative transient ischaemic attack who were refractory to medical therapy. All patients had MCA plaque stenosis at the M1 segment. Brain PWI was obtained from four major regions of interest (ROIs) at the frontal parietal, temporal, lateral ventricle and basal ganglia lobes prior to and following stent implantation. In addition, cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT) and time to peak (TTP) parameters derived from PWI were calculated. All patients underwent digital subtraction angiography following surgery to confirm the patency. Computed tomography angiography or PWI was performed 1 week and 3 months post-surgery. According to pre-operative PWI, there was significant hypoperfusion in the symptomatic frontal parietal, temporal, lateral ventricle and basal ganglia lobes. By contrast, the regional CBF and CBF increased in the ROIs of the affected cerebral hemisphere 3 months after stent implantation (P<0.05 vs. pre-operative data). Additionally, post-operative MTT and TTP in the ROIs on the operative side were significantly shorter than pre-operative MTT and TTP (P<0.05). During the follow-up period, the frequency of transient ischaemic attack was reduced or disappeared in all patients during the follow-up. In conclusion, PWI enables an effective and objective assessment of haemodynamics prior to and following stent angioplasty in patients with plaque stenosis of MCA at the M1 segment.

MicroRNA-326 inhibits cell proliferation and invasion, activating apoptosis in hepatocellular carcinoma by directly targeting LIM and SH3 protein 1.

Hepatocellular carcinoma (HCC) is the fifth-most common cancer and third leading cause of cancer-related deaths worldwide. Increasing evidence indicates that dysregulation of microRNAs is often observed in HCC, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. Recently, microRNA-326 (miR-326) has been demonstrated to play important roles in multiple types of human cancer. However, the expression pattern, clinical significance, roles and regulatory mechanisms of miR-326 in HCC have yet to be elucidated. In this study, miR-326 was frequently downregulated in HCC tissues and cell lines. Low miR-326 expression was significantly associated with the TNM stage, differentiation and lymph node metastasis of HCC patients. Further functional assays demonstrated that the recovered miR-326 expression inhibited HCC cell proliferation and invasion and activated cell apoptosis in vitro. In addition, LIM and SH3 protein 1 (LASP1) was identified as a direct target gene of miR-326 in HCC. Furthermore, LASP1 was upregulated in HCC tissues and cell lines. The expression level of LASP1 mRNA was inversely correlated with that of miR-326 in HCC tissues. Moreover, LASP1 silencing elicited effects similar to miR-326 overexpression on HCC cells, and LASP1 upregulation markedly reversed the effects of miR-326 overexpression on HCC cells. These results revealed that miR-326 suppressed the progression of HCC by directly targeting LASP1. Therefore, miR-326 may be used as a potential therapeutic target for the treatment of patients with HCC.