Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data.

Background: Epilepsy encompasses a group of heterogeneous brain diseases that afflict about 1% of the world's population. Accumulating evidence shows that the immune system plays a key role in epileptogenesis. Nevertheless, the immune-related mechanisms remain not been precisely understood. Methods: Three epilepsy datasets (GSE16969, GSE32534 and GSE143272) were screened to obtain differentially expressed immune-related genes (DEIRGs). Random forest (RF) and protein-protein interaction (PPI) network were constructed to identify core genes. Another dataset (GSE31718) and 60 clinical samples via quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to validate core genes. Immune cell infiltration score was performed with CIBERSORTx tools and single-sample gene set enrichment analysis (ssGSEA). Gene set variation analysis (GSVA) and ssGSEA were conducted to determine the pathways that are significantly enriched during normal and epilepsy. The correlation between hub genes, immune cells, and enriched molecular pathways was evaluated by Pearson correlation analysis. Results: Based on RF and PPI, 4 DEIRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were identified as hub genes. Results of qRT-PCR validated that higher expression levels of CSF1R, IL6R, TLR2, and TNFRSF1A in epilepsy samples compared to control sample. Immune infiltration analysis by CIBERSORTx displayed immune signatures that are significantly richer in epilepsy, T cell subsets in particular. Notably, ssGSEA found that Th1 signatures were more abundant in normal tissues; yet Th2 signatures were more abundant in epilepsy tissues. Cytokine cytokine receptor interaction (CCR) was significantly enriched in epilepsy based on multi-transcriptome data. Additionally, hub genes were significantly correlated with score of Th1/Th2 signatures and enrichment score of CCR in multi-transcriptome data. Conclusion: Four IRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were closely correlated pathogenesis of epilepsy, which may be by impacting CCR and the balance of Th1/Th2 signatures involved in the occurrence of epilepsy. Our data offer compelling insights into the pathogenesis and promising therapeutic targets for epilepsy.

Time to Endovascular Reperfusion and Outcome in Acute Ischemic Stroke : A Nationwide Prospective Registry in China.

PURPOSE: The benefit of endovascular reperfusion therapy for acute ischemic stroke is highly time-dependent but the relation of delays in workflow with outcomes and the key determinants of delays remain uncertain. This study aimed to evaluate the association between faster endovascular therapy and outcomes in a Chinese population with acute ischemic stroke. METHODS: Patients treated with endovascular therapy within 7 h due to anterior large vessel occlusion were enrolled in the ANGEL-ACT registry. Time intervals from hospital arrival to arterial puncture (door-to-puncture), hospital arrival to reperfusion (door-to-reperfusion) and puncture-to-reperfusion were recorded. The outcomes included modified Rankin Scale (mRS) scores 0-1, 0-2, mortality at 3 months, substantial reperfusion, and symptomatic intracranial hemorrhage (sICH). RESULTS: Of 932 patients receiving endovascular therapy (mean age 65.1 years, 60.1% male), the median door-to-puncture, door-to-reperfusion, and puncture-to-perfusion times were 110min (interquartile range, IQR 72-155min), 200min (IQR, 149-260min), and 76min (IQR, 50-118min). Of the patients 87.4% achieved substantial reperfusion and 9.6% had sICH. The mRS 0-1, 0-2, and mortality at 3 months were 39.8%, 43.2%, and 16.4%. Faster door-to-reperfusion and puncture-to-reperfusion were associated with higher likelihood of mRS 0-1, mRS 0-2, and lower rate of sICH. There was a trend of improved mRS, lower mortality, and fewer ICH with shorter door-to-puncture time; however, most differences were not statistically significant. CONCLUSION: Among patients with acute ischemic stroke in routine clinical practice, shorter time to reperfusion was associated with better outcome after endovascular therapy. Standardized workflows and training in endovascular treatment techniques should be promoted nationally to reduce in-hospital delays.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

Homocysteine level at the acute stage of ischemic stroke as a biomarker of poststroke depression: A systematic review and meta-analysis.

Background: Studies on the association of homocysteine level with poststroke depression (PSD) have yielded conflicting results. This systematic review and meta-analysis aimed to evaluate the elevated homocysteine level at the acute stage of ischemic stroke in predicting PSD. Methods: Two authors systematically searched articles indexed in PubMed and Embase databases up to 31 January 2022. Studies evaluating the association of homocysteine level with the development of PSD in patients with acute ischemic stroke were selected. Results: A total of 10 studies involving 2,907 patients were identified. The pooled adjusted odds ratio (OR) of PSD was 3.72 [95% confidence intervals (CI) 2.03-6.81] for the top vs. bottom homocysteine level. The value of elevated homocysteine level in predicting PSD was stronger in ≥6-month follow-up (OR 4.81; 95% CI 3.12-7.43) than those in ≤ 3-month follow-up subgroup (OR 3.20; 95% CI 1.29-7.91). Moreover, a per unit increase in homocysteine level conferred a 7% higher risk of PSD. Conclusion: Elevated homocysteine level in the acute stage of ischemic stroke may be an independent predictor of PSD.

Corrigendum to "Ginsenoside Rd improves behavioral impairment of rats with acute plateau status by modulating synaptic plasticity" [Chinese Herbal Medicines 11 (2019) 438-441].

[This corrects the article DOI: 10.1016/j.chmed.2019.03.005.].

Balloon-mounted stenting for ICAS in a multicenter registry study in China: a comparison with the WEAVE/WOVEN trial.

BACKGROUND: The outcome of deploying balloon-mounted stents for symptomatic intracranial atherosclerotic stenosis (ICAS) has not been fully investigated. In this study we evaluate the safety and long-term outcome of using balloon-mounted stents to treat symptomatic ICAS in comparison with the WEAVE/WOVEN study. METHODS: In a multicenter registry study of stenting for symptomatic intracranial artery stenosis in China, 159 patients treated with an intracranial balloon-mounted stent approved by the China Food and Drug Administration were evaluated. The morphological features of the lesions were categorized by Mori classification. The endpoints, including periprocedural and long-term clinical and radiological outcomes, were the same as those in the WEAVE/WOVEN study. RESULTS: In the present study the mean percent stenosis before and after stenting was 84.0% and 6.1%, respectively. The proportions of Mori A, Mori B, and Mori C lesions were 33.3%, 52.2%, and 14.5%, respectively. The 72-hour rates of stroke and mortality after the procedure were 0%. The 1-year rates of any stroke, ischemic stroke, hemorrhagic stroke, and death were 6.3% (10/159), 5.7% (9/159), 0.6% (1/159), and 0.6% (1/159), respectively. The 1-year rate of in-stent restenosis (ISR) was 23.4% (15/64). The rate of ISR in Mori C lesions (53.8%, 7/13) was significantly higher than that in Mori A (15.8%, 3/19) or Mori B lesions (15.6%, 5/32) (p=0.024). CONCLUSIONS: The short-term and long-term outcomes of using a balloon-mounted stent for symptomatic ICAS with focal and non-angular lesions (Mori A and B type) and smooth arterial access were comparable to the results of the WEAVE/WOVEN trial.

Murine cytomegalovirus infection in mice results in an acute inflammatory reaction in peripheral nerves.

Human cytomegalovirus (CMV) infection is asymptomatic in immunocompetent individuals. However, it can lead to disease in immunodeficient population. Little is known of the mechanisms underlying the pathogenicity of the virus. We investigated the impact of CMV infection on mouse nervous system. Peripheral nerves but not spinal cord was permissive to MCMV during acute infection. Activated CD8+ T cells, monocytes/macrophages and cytokine expression were increased in the blood and sciatic nerves of infected mice, which exhibited transient sensory dysfunction. This study indicates that systemic MCMV infection leads to a dissemination of MCMV into peripheral nerves, which is associated with a local inflammation but not nerve tissue damage in the acute phase.

Stenting for symptomatic intracranial arterial stenosis in China: 1-year outcome of a multicentre registry study.

Background and purpose: A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis (ICAS) combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable. However, it remained uncertain whether the low event rate could be of a long term. We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals. Methods: Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid, middle cerebral, intracranial vertebral or basilar arteries combined with poor collaterals were enrolled. Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators. The primary outcome was the rate of 30-day stroke, transient ischaemic attack and death, and 12-month ischaemic stroke within the same vascular territory, haemorrhagic stroke and vascular death after stenting. Results: From September 2013 to January 2015, 300 patients (ages 58.3±9.78 years) were recruited. Among them, 159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent. During the 1-year follow-up, 25 patients had a primary end point event. The probability of primary outcome at 1 year was 8.1% (95% CI 5.3% to 11.7%). In 76 patients with digital subtraction angiography follow-up, 27.6% (21/76) had re-stenosis ≥50% and 18.4% (14/76) had re-stenosis ≥70%. No baseline characteristic was associated with the primary outcome. Conclusion: The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals. Further randomised trial of comparing individually tailored stenting with best medical therapy is needed. Trial registration number: NCT01968122; Results.

Comorbidity Burden of Dementia: A Hospital-Based Retrospective Study from 2003 to 2012 in Seven Cities in China.

Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer's disease (AD), vascular dementia (VaD), or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January 2003 to December 2012. The Charlson Comorbidity Index (CCI) was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had VaD, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients, 3.4 ± 1.8 for those with VaD, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, and the length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.

Comorbidity burden of patients with Parkinson's disease and Parkinsonism between 2003 and 2012: A multicentre, nationwide, retrospective study in China.

Parkinson's disease (PD) and Parkinsonism are common neurodegenerative disorders with continuously increasing prevalence, causing high global burdens. However, data concerning the comorbidity burden of patients with PD or Parkinsonism in China are lacking. To investigate the health condition and comorbidity burden, a total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary hospitals in seven cities across China from 2003 to 2012. Their comorbidity burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and Parkinsonism patients. Compared with PD patients, Parkinsonism patients were older (69.8 ± 11.5 vs. 67.9 ± 11.4, P < 0.001); had a higher comorbidity burden, including ECI (1.1 ± 1.2 vs. 1.0 ± 1.2, P < 0.001) and CCI (1.3 ± 1.6 vs. 1.1 ± 1.5, P < 0.001); and had higher hospitalization expenses. The ECI (1.1 ± 1.3 vs. 0.9 ± 1.1, P < 0.001) and CCI (1.3 ± 1.6 vs. 0.9 ± 1.2, P < 0.001) were higher in males than in females. The average length of stay and daily hospitalization expenses increased with age, as did ECI and CCI. This is the first study to report the disease burden of Chinese PD and Parkinsonism patients. It provides useful information to better understand their health status, and to raise the awareness of clinicians for providing better health care.

Protective effect of tetrahydroxy stilbene glucoside on learning and memory by regulating synaptic plasticity.

Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer's disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B (NR2B) expression. An APP695V7171 transgenic mouse model of Alzheimer's disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragastrically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer's disease.

Protective Effects of Colivelin Against Alzheimer's Disease in a PDAPP Mouse Model.

BACKGROUND: Alzheimer's disease (AD) is characterized with progressive memory loss and severe cognitive impairments, which affect everyday life and human health in the elderly. It is required that an effective and safe protective reagent against AD should be developed. It has been reported that humanin (HN) exerts neuroprotective effects against AD. In this study, we investigated the effect of a novel and more effective HN derivative, Colivelin (CLN) on AD. METHODS: PDAPP(V717I) transgenic AD model mice (derived from parental C57/BL6 mice) were used in our study as AD model. Morris water maze test was used to test the memory impairment of AD mice and the levels of Aß40 and Aß42 were determined by an Elisa assay. We used an Immunohistochemistry and Immunofluorescence staining method to check the GFAP and MAP2 positive cells, and TUNEL to assess the apoptotic cells. Western blot assay was used to check the expression and phosphorylation level of p38. RESULTS: We found that CLN improved the memory impairment induced by AD and reduced the deposit of Aß40 and Aß42. CLN also inhibited cell apoptosis and activation of caspase 3 in brain tissues of AD mice. Inflammation in AD mice was alleviated by CLN treatment, including the accumulation of GFAP positive cells and the inflammatory cytokines. With both structure of AGA-HNG and ANDF, CLN exhibited significantly stronger effects than synchronously administration of AGA-HNG and ADNF, suggesting CLN as a novel potential effective therapeutic reagent for AD patients. Finally, we found that CLN inhibited phosphorylation of p38 in AD mice and p38 inhibitor, SB203580 weakened the therapeutic effect of CLN. CONCLUSION: CLN effectively improved the memory dysfunction in PDAPP mice, and our data suggests CLN as a novel and effective reagent which may have great potentials in AD therapy.

Common Aging Signature in the Peripheral Blood of Vascular Dementia and Alzheimer's Disease.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most dominant forms of dementia in elderly people. Due to the large overlap between AD and VaD in clinical observations, great controversies exist regarding the distinction and connection between these two types of senile dementia. Here for the first time, we resort to the gene expression pattern of the peripheral blood to compare AD and VaD objectively. In our previous work, we have demonstrated that the dysregulation of gene expression in AD is unique among the examined diseases including neurological diseases, cancer, and metabolic diseases. In this study, we found that the dysregulation of gene expression in AD and VaD is quite similar to each other at both functional and gene levels. Interestingly, the dysregulation started at the early stages of the diseases, namely mild cognitive impairment (MCI) and vascular cognitive impairment (VCI). We have also shown that this signature is distinctive from that of peripheral vascular diseases. Comparison with aging studies revealed that the most profound change in AD and VaD, namely ribosome, is consistent with the accelerated aging scenario. This study may have implications to the common mechanism between AD and VaD.

Safety and Efficacy Analyses of Angioplasty and Stenting for Severe Intracranial Arterial Stenosis: A Single-Center Retrospective Study in China.

BACKGROUND: The value of percutaneous transluminal angioplasty and stenting (PTAS) in the context of aggressive medical treatment for severe intracranial artery stenosis (ICAS) is under debate. This study compared the effects of PTAS and aggressive medical treatment in patients with severe ICAS and transient ischemic attack or stroke. MATERIAL AND METHODS: A retrospective cohort study was performed. Patients with severe ICAS were assigned to a PTAS group or aggressive medical treatment group, according to the angiographic features of the stenotic lesions. The primary outcome was defined as stroke or death within 30 days or cerebral ischemia occurring ipsilaterally to the qualifying artery beyond 30 days. RESULTS: We included 220 patients: 48 in the PTAS group and 172 in the medical group. The median follow-up was 32 months. PTAS was not associated with an increased incidence of the primary outcomes (10/42 vs. 39/172, p=0.96) or increased risks of the secondary outcomes of stroke, cardiovascular events, major bleeding, or mortality. The results of log-rank tests did not support a significant difference in event-free survival as a primary outcome between the 2 groups (chi-square=0.07, p=0.79). Moreover, although not significantly greater, the mean survival of patients in the PTAS group appeared to be better than that among patients in the medical group, as indicated by the curve for cumulative survival. CONCLUSIONS: A suitable PTAS procedure is safe for patients with severe ICAS, and no significant differences in incidence of recurrent stroke or death were found between PTAS and aggressive medication treatment.

Tetrahydroxy stilbene glucoside improved the behavioral disorders of APP695V717I transgenic mice by inhibiting the expression of Beclin-1 and LC3-II.

OBJECTIVE: To observe the effect of tetrahydroxy stilbene glucoside (TSG) on the behavior of APP695V717I transgenic mouse models and the expression of autophagy-associated proteins Beclin-1 and LC3-II. METHODS: Forty 3-month-old APP695V717I transgenic mice were randomized equally into either a TSG group (n = 20) or a model group (n = 20). A normal control group consisted of C57BL/6J mice of the same age and background (n = 20). The TSG group received TSG intragastric administration for 1 month. Behavior was measured using the Morris water maze and the Y-maze tests. Changes in pro- tein expression and mRNA of autophagy-associated Beclin-1 and LC3-II in mice hippocampus were detected by western blot and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analyses. RESULTS: The number of electric-stimulus escapes significantly increased and the Morris water maze test showed prolonged escape latency, greater swimming distance, less time taken to cross the exact former platform location in the model group, and increased mRNA and protein expressions of Beclin-1 and LC3-II compared with the control group (P < 0.05). The TSG group showed a decrease in the number of electric-stimulus escapes, shorter escape latency and swimming distance, greater time taken to cross the exact former platform location, and decreased mRNA and protein expressions of Beclin-1 and LC3-II compared with the model group (P < 0.05). CONCLUSION: these results indicate that tetrahydroxy stilbene glucoside can decrease expressions of Beclin-1 and LC3-II in the autophagy pathway. It can attenuate injury to endoplasmic reticulum functions caused by Ab neurotoxicity, improving learning, memorizing, and spatial orientation behavior in mice.

Thirty-Day Outcome of a Multicenter Registry Study of Stenting for Symptomatic Intracranial Artery Stenosis in China.

BACKGROUND AND PURPOSE: Although recent trials have suggested that stenting is worse than medical therapy for patients with severe symptomatic intracranial atherosclerotic stenosis, it is not clear whether this conclusion applies to a subset of patients with hypoperfusion symptoms. To justify for a new trial in China, we performed a multicenter prospective registry study to evaluate the safety and efficacy of endovascular stenting within 30 days for patients with severe symptomatic intracranial atherosclerotic stenosis. METHODS: Patients with symptomatic intracranial atherosclerotic stenosis caused by 70% to 99% stenosis combined with poor collaterals were enrolled. The patients were treated either with balloon-mounted stent or with balloon predilation plus self-expanding stent as determined by the operators following a guideline. The primary outcome within 30 days is stroke, transient ischemic attack, and death after stenting. The secondary outcome is successful revascularization. The baseline characteristics and outcomes of the 2 treatment groups were compared. RESULTS: From September 2013 to January 2015, among 354 consecutive patients, 300 patients (aged 58.3±9.78 years) were recruited, including 159 patients treated with balloon-mounted stent and 141 patients with balloon plus self-expanding stent. The 30-day rate of stroke, transient ischemic attack, and death was 4.3%. Successful revascularization was 97.3%. Patients treated with balloon-mounted stent were older, less likely to have middle cerebral artery lesions, more likely to have vertebral artery lesions, more likely to have Mori A lesions, less likely to have Mori C lesions, and likely to have lower degree of residual stenosis than patients treated with balloon plus self-expanding stent. CONCLUSIONS: The short-term safety and efficacy of endovascular stenting for patients with severe symptomatic intracranial atherosclerotic stenosis in China is acceptable. Balloon-mounted stent may have lower degree of residual stenosis than self-expanding stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122.

General public perceptions and attitudes toward Alzheimer's disease from five cities in China.

Alzheimer's disease (AD) is the most common type of dementia affecting the aged population worldwide, yet its social perceptions have been less studied. To investigate the perceptions and attitudes toward AD in the Chinese population, a cross-sectional face-to-face survey of 2,000 randomly selected adults was conducted in five representative cities of China. This survey focused on the fear of AD, and the relationship between this variable and each studied factor was analyzed using univariate analysis and multivariate regression analysis. In general, 76.6% of the total respondents had personal fear of developing AD, and such fear was closely related to the proximity to AD and perceived severity of AD, as well as other factors such as gender and self-perceived health. The results strongly suggested that more attention should be paid to public health education of AD, which can only be achieved with the cooperation of government, media, medical institutions, and the community so as to eliminate people's confusion about AD, relieve their psychological burden, and optimize their health-seeking behavior.

Down-regulation of thyroid hormone receptor ß1 gene expression in gastric cancer involves promoter methylation.

Hypermethylation has been shown in the promoter region of the thyroid hormone receptor ß1 (TRß1) gene in several human tumors. However, its role in gastric cancer formation is still unclear. In the study, we analyzed mRNA expression of TRß1 gene using real-time quantitative PCR (qPCR). A quantitative methylation-specific PCR (Q-MSP) assay was used to determine the methylation status of the TRß1 gene promoter region in 46 pair-matched gastric neoplastic and adjacent non-neoplastic tissues. The results showed that TRß1 mRNA expression was significantly reduced in gastric cancer specimens. The methylation of promoter of TRß1 gene in gastric cancer tissues was significantly higher than in adjacent normal tissues. Promoter hypermethylation of the TRß1 gene correlated with tumor infiltration, lymph node metastasis, and distant metastasis, but it was not associated with other clinicopathological characteristics. We treated gastric cancer cell lines MKN-45, MKN-28, SGC-7901, NCI-N87, and SNU-1 with 5-Aza-2-deoxycytidine (5-Aza-dC). The results showed the expression of TRß1 mRNA was increased in MKN-45, MKN-28, SGC-7901, but not increased in NCI-N87 and SNU-1. These results suggest that the TRß1 gene plays important roles in the development of gastric cancer partially through epigenetic mechanisms.

[Th17-mediated relapsing-remitting multiple sclerosis is nonresponsive to interferon-ß1b].

OBJECTIVE: To investigate the relationship between the efficacy of interferon beta-1b (INF-ß-1b) on relapsing-remitting multiple sclerosis (RRMS) and the Th17 cells in peripheral blood. METHODS: Eleven RRMS patients were enrolled and treated with 250 µg INF-ß-1b for 6 months. Expanded disability status scale (EDSS) scrore and T2 lesion number on MRI were examined both at baseline and at the end of the study. Flow cytometry was used to detect the number of Th17 cells in peripheral blood before the treatment. RESULTS: Acoording to the EDSS scores, the 11 cases of RRMS were divided into two groups: the effective group and the ineffective group.The EDSS scores and the number of lesions on T2-weighted MRI were not different significantly between the two groups (P>0.05) before the treatment. But after the treatment, compared with the ineffective group, the EDSS scores and the number of lesions on T2-weighted MRI decreased significantly in the effective group (P<0.05). Compared with the effective group, the number of Th17 cells in the ineffective group increased significantly (P<0.01) before treatment. CONCLUSION: Th17-mediated RRMS is nonresponsive to IFN-ß-1b treatment.

Tetrahydroxy stilbene glucoside reduces the cognitive impairment and overexpression of amyloid precursor protein induced by aluminum exposure.

OBJECTIVE: Excessive aluminum (Al) exposure impairs neurocognitive function in humans and animals. Epidemiologic studies have shown a potential linkage between chronic Al exposure and Alzheimer's disease. The present study aims to evaluate the effects of tetrahydroxy stilbene glucoside (TSG), the extract from herbal medicine Polygoni Multiflori, on cognitive impairment and the over-expression of hippocampal amyloid precursor protein (APP) induced by chronic exposure to Al in rats. METHODS: Rats were treated with 0.3% aluminum chloride (AlCl3) prepared in the drinking water for 90 d. AlCl3-treated animals were then randomly assigned to receive vehicle, TSG (4 g/kg), or Vitamin E (VE; 40 mg/kg) treatment for 5 months. VE served as a positive control. The effect of TSG was evaluated by passive avoidance task, and APP expression was evaluated by Western blotting. RESULTS: Following exposure to AlCl3 for 90 d, animals displayed a striking decrease (> 80%) in step-through latency in the passive avoidance task and a significant increase in the expression of APP in the hippocampus. Both TSG and VE significantly ameliorated the performance impairment in the passive avoidance task, and suppressed the over-expression of APP. Moreover, the effects of TSG, but not of VE, were in a time-dependent manner. CONCLUSION: TSG may possess therapeutic effects against Alzheimer's disease.