Sjögren's syndrome with rapidly progressive motor neuron disease: a case report.

Sjögren's syndrome is an autoimmune disease that can affect multiple systems. Sjögren's syndrome with motor neuron disease is rarely reported. Herein, we describe a patient with rapidly progressive motor neuron disease secondary to Sjögren's syndrome. A 42-year-old woman was admitted to our hospital with a 2-month history of progressive limb weakness. Neurological assessment revealed fasciculation in the lower limbs and amyotrophy in the bilateral supraspinatus, interosseous, and thenar muscles. Serological examination and labial gland biopsy revealed Sjögren's syndrome. In addition, electromyography demonstrated neurogenic damage to the upper and lower limbs. The patient received a short course of high-dose corticosteroids, intravenous immunoglobulins, and immunosuppressant treatment, including a weekly dose of 0.4 g cyclophosphamide and a daily dose of 0.2 g hydroxychloroquine. However, the patient's limb weakness was further aggravated and her respiratory function was compromised. Electromyography re-examination demonstrated extensive neurogenic damage, and she was diagnosed with Sjögren's syndrome with motor neuron disease. The patient died of respiratory failure after 2 months. We suggest that more effective maintenance treatments should be sought. Further investigation is required to elucidate the association between autoimmune motor neuron disease and Sjögren's syndrome.

TMT-Based Proteomic Analysis of Plasma from Children with Rolandic Epilepsy.

Rolandic epilepsy is one of the most common epileptic syndromes in childhood. We used TMT-based proteomics and bioinformatics analysis to identify the differentially expressed proteins in plasma of children with Rolandic epilepsy. Our aim was to provide a molecular basis for exploring possible mechanisms underlying the pathogenesis of epilepsy. Subjects were divided into two groups (five in each): patients with Rolandic epilepsy as cases and patients with migraine as controls. Total proteins were extracted and quantitatively labeled with TMT, then analyzed using liquid chromatography mass spectrometry. Bioinformatics analysis was used to identify the hub genes. A total of 752 proteins were identified, of which 670 contained quantitative proteins. 217 differentially expressed proteins were identified, 46 of which were only upregulated in more than two groups and 111 of which were only downregulated in more than two groups. Bioinformatics analysis revealed top 10 hub genes in the up- and downregulated groups, respectively. Our study demonstrates that some differentially expressed proteins are associated with epilepsy. Activation of acute-phase or innate immune response and complement and fibrinogen systems and repression of glycolysis, lipoprotein metabolism, and antioxidant activity may play a role in the development of epilepsy.

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus.

The filamentous actin (F-actin) cytoskeleton is progressively damaged after status epilepticus (SE), which is related to delayed neuronal death, aberrant recurrent circuits and epileptogenesis. Glucocorticoids regulate dendritic spine remodeling by acting on glucocorticoid receptors and the dynamics of the F-actin cytoskeleton. Our previous study showed that administration of dexamethasone (DEX) in the latent period of the pilocarpine epileptic model reduces damage to the hippocampal filamentous actin cytoskeleton and the loss of hippocampal neurons and aids in maintaining the synaptic structures, but it is not sufficient to stop epileptogenesis. In this work, we focused on the role of glucocorticoids in regulating the hippocampal F-actin cytoskeleton during SE. We examined the abundance of synaptic F-actin, analyzed the hippocampal F-actin/G-actin (F/G) ratio and pCofilin, and evaluated the number of hippocampal neurons and pre/postsynaptic markers in pilocarpine-induced status epilepticus mice with or without administration of dexamethasone (DEX). We found that the latency of Stage 3 seizures increased, the mortality decreased, the damage to the synaptic F-actin cytoskeleton in the hippocampal subfields was significantly attenuated, and a greater number of postsynaptic structures were retained in the hippocampal subfields after treatment with DEX. These results indicate that treatment with dexamethasone stabilizes the synaptic F-actin cytoskeleton and reduces the damage to the brain due to SE. This approach is expected to be beneficial in alleviating delayed neuron damage and the process of epileptogenesis.

An elongated tract of polyQ in the carboxyl­terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation.

An aberrant elongated tract of glutamine residues (polyQ) in proteins induces multiple diseases treated in the clinic. In our previous study of progressive myoclonic epilepsy (PME), using whole­exome sequencing, a mutant Cav2.1 protein with an aberrant elongated polyQ tract was identified in PME patients. To investigate the molecular mechanism and cell biology of this aberrant elongated polyQ tract, wild­type Cav2.1 with 13 polyQ repeats (Cav2.1 wt­Q13) and mutant­type Cav2.1 with 26 polyQ repeats (Cav2.1 mt­Q26) were prepared and introduced into human SH­SY5Y neuroblastoma cells. Using a WST­1 assay, it was revealed that Cav2.1 mt­Q26 markedly suppressed the proliferation of the SH­SY5Y cells, a result not observed for the Cav2.1 wt­Q13­transfected cells. It was also revealed that Cav2.1 mt and its truncated molecules suppressed cell proliferation by inducing apoptosis rather than arresting the cell cycle. Further investigations indicated a nuclear translocation phenomenon associated with the Cav2.1 mt molecules. Mechanistically, it was revealed that the Cav2.1 mt molecules activated the Bcl­2/Bax, caspase­3 and poly ADP­ribose polymerase (PARP) apoptotic pathways. The present study may provide new insights for interpreting the pathogenesis of PME and the relationship among polyQ, CACNA1A gene mutations and PME.

Dexamethasone ameliorates the damage of hippocampal filamentous actin cytoskeleton but is not sufficient to cease epileptogenesis in pilocarpine induced epileptic mice.

Rogressive deconstruction of filament actin (F-actin) in hippocampal neurons in the epileptic brain have been associated with epileptogenesis. Previous clinical studies suggest that glucocorticoids treatment plays beneficial roles in refractory epilepsy. Glucocorticoids treatment affects dendritic spine morphology by regulating local glucocorticoid receptors and F-actin cytoskeleton dynamics. However, how glucocorticoids regulate epileptogenesis by controlling F-actin cytoskeleton is not clear yet. Here we study the function of glucocorticoids in epileptogenesis by examining F-actin abundance, hippocampal neuron number, and synaptic markers in pilocarpine-induced epileptic mice in the presence or absence of dexamethasone (DEX) treatment. We found that spontaneous seizure duration was significantly reduced; F-actin damage in hippocampal subfields was remarkably attenuated; loss of pyramidal cells was dramatically decreased; more intact synaptic structures indicated by pre- and postsynaptic markers were preserved in multiple hippocampal regions after DEX treatment. However, the number of ZNT3 positive particles in the molecular layer in the hippocampus of pilocarpine epileptic mice was not altered after DEX treatment. Although not sufficient to cease epileptogenesis, our results suggest that dexamethasone treatment ameliorates the damage of epileptic brain by stabilizing F-actin cytoskeleton in the pilocarpine epileptic mice.

Detection of seizure patterns with multichannel amplitude-integrated EEG and the color density spectral array in the adult neurology intensive care unit.

This study's purpose was to determine the sensitivity, false-positive and false-negative of seizure detection in adult intensive care by amplitude-integrated electroencephalography (aEEG) and color density spectral array (CDSA).30 continuous electroencephalogram (EEG) recordings were randomly performed in 3 digital EEG-recording machines, 3 specialized neurophysiologists participated in this study, underwent 4 hours of training of CDSA and aEEG, marked any epochs suspected to be seizures without access to the raw EEG. The results will be compared and analyzed with continuous EEG reading to consider sensitivity, positive or negative rate.The recordings in this study, comprised 720 hours of EEG containing a total of 435 seizures. The median sensitivity for seizure identification was 80% of CDSA and 81.3% of aEEG, Median false-positive was 4 per 24 hours of CDSA, and 2 per 24 hours of aEEG display, Median false-negative was 4 per 24 hours of CDSA, and 4 per 24 hours of aEEG display. The time spent in identification of seizures by CDSA and aEEG was much time-saving than continuous EEG-reading.In this study, both CDSA and aEEG have a higher sensitivity but lower false-positive or missed rate in the interpretation of seizure identification in adult NICU.

Blood pressure reduction in acute ischemic stroke according to time to treatment: a subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke trial.

OBJECTIVE: The optimal time to initiate antihypertensive therapy among patients with acute ischemic stroke remains uncertain. We tested the effects of blood pressure reduction among patients with acute ischemic stroke according to time from onset to initiation of antihypertensive treatment. METHODS: We randomly assigned 4071 acute ischemic stroke patients with elevated SBP to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. The primary outcome was a combination of death and major disability, and secondary outcomes included the modified Rankin score, recurrent stroke, vascular disease events, and all-cause mortality. RESULTS: At 24 h after randomization, the differences in SBP reductions were 8.7, 9.5, and 9.6 mmHg between the antihypertensive treatment and control groups among patients receiving treatment within less than 12, 12-23, and 24-48 h after stroke onset, respectively (P < 0.001 in all subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups in all subgroups. At the 3-month follow-up, death or major disability [odds ratio (OR) 0.73; 95% confidence interval (CI) 0.55-0.96; P = 0.03], recurrent stroke (OR 0.25; 95% CI 0.08-0.74; P = 0.01), and vascular events (OR 0.41; 95% CI 0.18-0.95; P = 0.04) were significantly reduced in the antihypertensive treatment group only among participants who received treatment between 24 and 48 h. CONCLUSION: Blood pressure reduction might reduce 3-month death and major disability and recurrent stroke among patients with acute ischemic stroke who receive antihypertensive treatment between 24 and 48 h after stroke onset. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01840072.

Horizontal eyeball akinesia as an initial manifestation of CLIPPERS: Case report and review of literature.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare chronic inflammatory disorder in the central nervous system (CNS), which is characterized by magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement "peppering" the pons. Lesions of CLIPPERS mainly involve the pons and the cerebellum. Adjacent structures such as the medulla and the midbrain may also be involved. It is proposed that CLIPPERS is an immune-mediated inflammatory condition characteristic of T-cell-predominant infiltrates and good responsiveness to corticosteroids. METHODS AND RESULTS: We report a 46-year-old woman who presented with horizontal eyeball akinesia and gait ataxia with characteristic MRI features of CLIPPERS. The possible pathogenesis, clinical manifestations, imaging features, treatment, and prognosis of this peculiar disorder are summarized. CONCLUSION: This report contributes to the clinical understanding of CLIPPERS which may present with horizontal eyeball akinesia as an initial manifestation. The characteristic presentation of a subacute cerebellar and brainstem syndrome and pepper-like gadolinium enhancement was confirmed in this report. Long-term immunosuppressive treatment seems to be mandatory to sustain improvement. Azathioprine alone may be capable of maintaining remission.

Vortioxetine versus Duloxetine in the Treatment of Patients with Major Depressive Disorder: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Vortioxetine and duloxetine are two new antidepressant drugs that have been used clinically in the treatment of major depressive disorder (MDD). The objectives of this meta-analysis were to evaluate the efficacy and tolerability of vortioxetine compared with duloxetine in MDD. METHODS: Randomized controlled trials (RCTs) published in PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were systematically reviewed to compare vortioxetine with duloxetine in terms of efficacy and tolerability in patients with MDD. Results were expressed as the risk ratio (RR) with 95 % confidence intervals (CIs), and weighted mean difference (WMD). Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, depending on the heterogeneity among studies. RESULTS: A total of five RCTs involving 2287 patients met the inclusion criteria and were included in this meta-analysis. Pooled results showed that duloxetine was associated with a higher response rate than vortioxetine, as well as showing a similar remission rate with vortioxetine. The changes from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS), 24-item Hamilton Rating Scale for Depression (HAM-D24), Clinical Global Impression-Improvement scale (CGI-I), CGI-Severity scale (CGI-S), Sheehan Disability Scale (SDS), and Hamilton Anxiety Rating Scale (HAM-A) scores were significantly greater in the duloxetine group than in the vortioxetine group. The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group. CONCLUSION: Duloxetine was more effective but less well-tolerated than vortioxetine in MDD. Considering the potential limitations of this meta-analysis, more large-scale RCTs are needed to confirm these findings.

A rare case of tumor-mimicking primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (PACNS) is a rare, but severe vascular disease. The present study reports the case of a 42-year-old male who developed PACNS. Magnetic resonance imaging (MRI) scans initially led to a misleading diagnosis of malignant glioma, and surgery was performed. The mass was resected, and a pathological examination confirmed a cerebral vasculitis. Single therapy with high doses of steroid did not improve the patient's condition, while a subsequent lesion appeared on the opposite side one year later. Combined therapy with methylprednisone and cyclophosphamide resulted in a great improvement for the patient. No relapse occurred during one year's follow-up. Although a tumor-mimicking PACNS has no established imaging features, a diagnosis of tumor-mimicking PACNS should be suspected when the MRI reveals inappropriate presentations of a tumor. Greater awareness of this potential manifestation of PACNS may facilitate more prompt diagnosis and treatment.

The efficacy and safety of 10 mg vortioxetine in the treatment of major depressive disorder: a meta-analysis of randomized controlled trials.

BACKGROUND: Vortioxetine is an investigational multimodal antidepressant. We conducted this meta-analysis to assess the efficacy and safety of 10 mg vortioxetine in the treatment of major depressive disorder (MDD). METHODS: Randomized controlled trials (RCTs) published in PubMed, Web of Science, Embase, and ClinicalTrials.gov were systematically reviewed to assess the treatment effects and safety profiles of patients with MDD who were treated with 10 mg vortioxetine. The outcome measures included response rate, remission rate, changes from baseline in Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Rating Scale for Depression (24-items) (HAM-D24), Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement (CGI-I) scores. Results were expressed with risk ratio or weighted mean difference with 95% confidence intervals. Pooled results were calculated using a fixed-effects model or a random-effects model according to the heterogeneity among included trials. RESULTS: Six RCTs with a total of 1,801 patients met the inclusion criteria and were included in this meta-analysis. The 10 mg vortioxetine dose significantly increased the response rate and remission rate in the treatment of MDD compared with placebo. Moreover, there was a statistically significant reduction from baseline in the MADRS, HAM-D24, CGI-S, and CGI-I scores with 10 mg vortioxetine vs placebo. The incidence of treatment-emergent adverse events such as nausea, vomiting, constipation, and hyperhidrosis was higher in the 10 mg vortioxetine group than in the placebo group. CONCLUSION: Vortioxetine 10 mg can significantly increase the response rate and remission rate, and reduce the MADRS, HAM-D24, CGI-S, and CGI-I scores in patients with MDD with an acceptable risk of treatment-emergent adverse events. Further well-conducted, large-scale trials are needed to validate these findings.

Salvianolic acid B ameliorates CNS autoimmunity by suppressing Th1 responses.

Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), is a Th1 and Th17 cell-mediated CNS autoimmune disease. Therefore, immune regulation is a key target for therapy. Salvianolic acid B (Sal B) is a major water-soluble bioactive component of the famous traditional Chinese medicine Salvia miltiorrhiza, which is notable for its anti-oxidative and anti-inflammatory effects. Thus Sal B, by impairing Th1 or Th17 responses in EAE/MS, might ameliorate the crippling symptoms. Here we show that the intraperitoneal administration of 30mg/kg Sal B daily for 14 days after the onset of MOG-induced EAE in mice effectively reduced its severity. Additionally, Sal B treatment downgraded the infiltration of inflammatory cells, limited astrogliosis and blocked Th1 responses other than that of Th17. These results indicated that Sal B may serve as an effective therapeutic agent for MS/EAE by inhibiting Th1 cell responses.

Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer's disease rats.

As a part of Alzheimer's disease (AD) development the mammalian target of rapamycin (mTOR) has been reported to play a crucial role in regulating cognition and can be used as a neuronal marker. Neuro-inflammation is also a cause of the pathophysiological process in AD. Thus, we examined the protein expression levels of mTOR and its downstream pathways as well as pro-inflammatory cytokines (PICs) in the brain of AD rats. We further examined the effects of blocking mTOR on PICs, namely IL-1ß, IL-6 and TNF-α. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in the hippocampus of AD rats compared with controls. Blocking mTOR by using rapamycin selectively enhanced activities of IL-6 and TNF-α signaling pathways, which was accompanied with an increase of Caspase-3, indicating cellular apoptosis and worsened learning performance. In conclusion, our data for the first time revealed specific signaling pathways engaged in the development of AD, including a regulatory role by the activation of mTOR in PIC mechanisms. Stimulation of mTOR is likely to play a beneficial role in modulating neurological deficits in AD.Targeting one or more of these signaling molecules may present with new opportunities for treatment and clinical management of AD.

Statistical Use in Clinical Studies: Is There Evidence of a Methodological Shift?

BACKGROUND: Several studies indicate that the statistical education model and level in medical training fails to meet the demands of clinicians, especially when they want to understand published clinical research. We investigated how study designs and statistical methods in clinical studies have changed in the last twenty years, and we identified the current trends in study designs and statistical methods in clinical studies. METHODS: We reviewed 838 eligible clinical study articles that were published in 1990, 2000, and 2010 in four journals New England Journal of Medicine, Lancet, Journal of the American Medical Association and Nature Medicine. The study types, study designs, sample designs, data quality controls, statistical methods and statistical software were examined. RESULTS: Substantial changes occurred in the past twenty years. The majority of the studies focused on drug trials (61.6%, n = 516). In 1990, 2000, and 2010, there was an incremental increase in RCT studies (74.4%, 82.8%, and 84.0%, respectively, p = 0.013). Over time, there was increased attention on the details of selecting a sample and controlling bias, and there was a higher frequency of utilizing complex statistical methods. In 2010, the most common statistical methods were confidence interval for superiority and non-inferiority comparison (41.6%), survival analysis (28.5%), correction analysis for covariates (18.8%) and Logistic regression (15.3%). CONCLUSIONS: These findings indicate that statistical measures in clinical studies are continuously developing and that the credibility of clinical study results is increasing. These findings provide information for future changes in statistical training in medical education.

The AIDS epidemic and economic input impact factors in Chongqing, China, from 2006 to 2012: a spatial-temporal analysis.

OBJECTIVE: To analyse the spatial-temporal clustering of the HIV/AIDS epidemic in Chongqing and to explore its association with the economic indices of AIDS prevention and treatment. METHODS: Data on the HIV/AIDS epidemic and economic indices of AIDS prevention and treatment were obtained from the annual reports of the Chongqing Municipal Center for Disease Control for 2006-2012. Spatial clustering analysis, temporal-spatial clustering analysis, and spatial regression were used to conduct statistical analysis. RESULTS: The annual average new HIV infection rate, incidence rate for new AIDS cases, and rate of people living with HIV in Chongqing were 5.97, 2.42 and 28.12 per 100,000, respectively, for 2006-2012. The HIV/AIDS epidemic showed a non-random spatial distribution (Moran's I≥0.310; p<0.05). The epidemic hotspots were distributed in the 15 mid-western counties. The most likely clusters were primarily located in the central region and southwest of Chongqing and occurred in 2010-2012. The regression coefficients of the total amount of special funds allocated to AIDS and to the public awareness unit for the numbers of new HIV cases, new AIDS cases, and people living with HIV were 0.775, 0.976 and 0.816, and -0.188, -0.259 and -0.215 (p<0.002), respectively. CONCLUSIONS: The Chongqing HIV/AIDS epidemic showed temporal-spatial clustering and was mainly clustered in the mid-western and south-western counties, showing an upward trend over time. The amount of special funds dedicated to AIDS and to the public awareness unit showed positive and negative relationships with HIV/AIDS spatial clustering, respectively.

Role of the immunogenic and tolerogenic subsets of dendritic cells in multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated disorder in the central nervous system (CNS) characterized by inflammation and demyelination as well as axonal and neuronal degeneration. So far effective therapies to reverse the disease are still lacking; most therapeutic drugs can only ameliorate the symptoms or reduce the frequency of relapse. Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are key players in both mediating immune responses and inducing immune tolerance. Increasing evidence indicates that DCs contribute to the pathogenesis of MS and might provide an avenue for therapeutic intervention. Here, we summarize the immunogenic and tolerogenic roles of DCs in MS and review medicinal drugs that may affect functions of DCs and have been applied in clinic for MS treatment. We also describe potential therapeutic molecules that can target DCs by inducing anti-inflammatory cytokines and inhibiting proinflammatory cytokines in MS.

Deterioration of palatal myoclonus after acute thalamic hemorrhage.

BACKGROUND: Palatal myoclonus (PM) is the hallmark of hypertrophic olivary degeneration (HOD); however, little is known regarding the association of thalamic lesions and PM. Case presentation: Here, we report a case of deteriorative PM after an acute small ventrolateral thalamic hemorrhage in a female Chinese patient with HOD. The sudden and severe deterioration of PM was preceded by at least 10 days of an occasionally occurring PM, which was related to an acute cerebellar hemorrhage 8 months earlier. A computed tomography scan upon admission showed a small intracerebral hematoma in the left ventrolateral thalamus, and a magnetic resonance imaging scan revealed the typical signs of HOD as well as a remote lesion in the dentate nucleus. Symptoms of PM were controlled by carbamazepine and clonazepam. CONCLUSION: These findings indicated that the damaged dentatothalamic tract might be due to a unique pathogenic mechanism involving a lesion of the ventrolateral thalamus and Guillain-Mollaret triangle.

Risk factors of stroke in Western and Asian countries: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: There has been an increasing trend in the incidence of stroke worldwide in recent years, and the number of studies focusing on the risk factors for stroke has also increased every year. To comprehensively evaluate the risk factors of stroke identified in prospective Western and Asian cohort studies. METHODS: Population-based cohort studies on stroke were searched in databases (PubMed, EMBASE, Web of Science, Google Scholar, etc.), and the library of the Third Military Medical University was manually searched for relevant information. A meta-analysis of Western and Asian studies on risk factors was performed. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the final group of cohort studies. RESULTS: After screening, 22 prospective cohort studies were included in the analyses of this investigation. Two factors, smoking and alcohol consumption, showed statistically significant differences between Western and Asian populations, and the results were as follows (W/A): 2.05 (95% CI, 1.68 ~ 2.49)/1.27 (95% CI, 1.04 ~ 1.55) and 0.89 (95% CI, 0.76 ~ 1.04)/1.28 (95% CI, 1.07 ~ 1.53). The factor BMI = 18.5-21.9 kg/m2 showed statistically significant differences only in Western populations, 0.96 (95% CI, 0.93 ~ 0.99); the factor SBP = 120-139 mm Hg showed statistically significant differences only in Asian populations, 2.29 (95% CI, 1.04 ~ 5.09). CONCLUSIONS: The prevalences of risk factors affect the stroke morbidity in Western and Asian populations, which may be biased by race. The meta-analysis of population-based studies suggests that different preventive measures should be adopted for Western and Asian population groups that are at high risk for stroke.

Upregulation of the Kank1 gene-induced brain glioma apoptosis and blockade of the cell cycle in G0/G1 phase.

The Kank1 gene is one of the important members of the Kank gene family. As an important adaptor protein, Kank1 plays a significant role in the genesis and development of many malignant tumors. It was recently discovered that the Kank1 gene is a new cancer suppressor, and its expression is significantly downregulated or it is not expressed in kidney cancer, bladder cancer, prostate cancer, lung cancer and breast cancer. However, no report on the role of Kank1 in the genesis of brain glioma is available to date. In this study, we found significantly lower expression of the Kank1 gene in human brain glioma cells compared to the other cells evaluated. We used RNA interference techniques to silence Kank1 gene expression and found acceleration of tumor cell proliferation. However, when the Kank1 gene was upregulated, cell apoptosis occurred and the cell cycle was blocked in the G0/G1 phase. Also, we found that upregulating the Kank1 gene may result in the change of mitochondrial membrane potential, and the regulation of Bax and Bcl-2 may promote the mitochondria to release cytochrome C so as to activate Caspase-9 and -3. Thus, the human brain glioma apoptosis induced by upregulation of the Kank1 gene is closely relevant to the mitochondrial pathway.

Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial.

IMPORTANCE: Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. OBJECTIVE: To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS: The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. INTERVENTIONS: Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURES: Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 14 days or hospital discharge. RESULTS: Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (-12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (-7.2%) in the control group within 24 hours after randomization (difference, -5.5% [95% CI, -4.9 to -6.1%]; absolute difference, -9.1 mm Hg [95% CI, -10.2 to -8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, -9.3 mm Hg [95% CI, -10.1 to -8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93). CONCLUSION AND RELEVANCE: Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01840072.