A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

Fastigial nucleus stimulation ameliorates cognitive impairment via modulating autophagy and inflammasomes activation in a rat model of vascular dementia.

BACKGROUND: It has been reported that the fastigial nucleus (FSN) plays an important role in the development of vascular dementia (VD). Both autophagy and inflammation are functionally involved in the pathogenesis of VD. In this study, we aimed to evaluate the therapeutic effect of electrical cerebellar fastigial nucleus stimulation (FNS) in VD treatment, as well as the effect of FNS on autophagy and inflammation. METHODS: A Morris water maze was used to evaluate the effect of FNS on the learning and memory ability of VD rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to study the apoptosis status of neuron cells in different groups of rats. In addition, immunohistochemistry (IHC) assay, real-time polymerase chain reaction, and Western blot analysis were carried out to measure the expression of various factors involved in autophagy and inflammation. RESULTS: Rats with artery occlusion or FSN damages showed longer escape latency and spent less time in the target quadrant. In addition, FNS treatment could help to partly recover the lost learning and memory ability in VD rats. Meanwhile, FNS treatment could alleviate neuron cell apoptosis by downregulating light chain 3-II expression and NLRP3 expression. In addition, the expression of caspase-1, interleukin 1ß (IL-1ß), and IL-18 was markedly reduced in VD rats treated by FNS. CONCLUSION: FNS treatment exerted a therapeutic effect during VD treatment by suppressing the autophagy process and by inhibiting inflammatory responses, thus alleviating neuron cell apoptosis and reducing the severity of VD.

Intra-artery infusion of recombinant human erythropoietin reduces blood-brain barrier disruption in rats following cerebral ischemia and reperfusion.

OBJECTIVES: Intra-artery infusion of recombinant human erythropoietin (rhEPO) has recently been reported to confer neuroprotection against cerebral ischemia-reperfusion injury in animal models; however, the molecular mechanisms are still under investigation. The present study focused on the specific mechanism involved in blood-brain barrier (BBB) disruption. METHODS: Thirty-six male and nine female Sprague Dawley rats were subjected to middle cerebral artery (MCA) occlusion to induce focal cerebral ischemia, and administrated rhEPO at a dose of 800 U/kg through MCA infusion at the beginning of reperfusion. Neurobehavioral deficits, brain edema, and infarct volume were evaluated after 2 h of ischemia and 24 h of reperfusion. BBB permeability was assessed by quantifying the extravasation of Evans blue (EB) dye. The expression of tight junction proteins and matrix metalloproteinases (MMPs) (Claudin-5, Occludin, MMP-2, and MMP-9) in microvessels were detected by immunofluorescence and western blot. The activities of MMPs in the cerebral microvessels were determined by gelatin zymography. RESULTS: Treatment with rhEPO through the MCA strongly alleviated infarct volume, brain edema, and improved neurobehavioral outcomes in male and female rats. In addition, rhEPO remarkably suppressed the EB extravasation induced by brain ischemia. Furthermore, rhEPO prevented degradation of Claudin-5 and Occludin, and reduced the expression and activity of MMP-2 and MMP-9 in isolated brain microvessels. CONCLUSIONS: Treatment with rhEPO through MCA infusion prevented brain edema formation and infarction through inhibition of MMP-mediated BBB disruption in acute ischemic stroke.

The effect of procyanidin on expression of STAT1 in type 2 diabetes mellitus SD rats with focal cerebral ischemia.

OBJECTIVES: Diabetes with cerebral infarction is a common disease that severely impacts health. This study investigated the effect of procyanidin (PC) on the expression of signal transducers and activators of transcription (STAT1) in type 2 diabetes mellitus SD rats with focal cerebral ischemia. We then explored the protective mechanisms of PC in type 2 diabetes mellitus SD rats with focal cerebral ischemia, to provide theory evidence for its clinical application. METHODS: We set up a type 2 diabetes mellitus-MCAO model, evaluated neurological function, and used immunohistochemistry methods to measure the activity of STAT1. RESULTS: The brain expression of STAT1 in rats of the sham-operation group was low, but more STAT1 positive cells were found in normal rats with ischemia and in rats with both type 2 diabetes and ischemia when groups were compared with the sham-operation group (p<0.01). Compared with rats that had type 2 diabetes and ischemia, the numbers of STAT1 positive cells after low, medium and high-doses of PC were all decreased (p<0.01), whereby the mid and high-dose groups showed a more substantial decrease (p<0.01) and with no variance between the two groups (p>0.05). CONCLUSIONS: These results indicate that PC has a neuroprotective effect on type 2 diabetes mellitus-MCAO; this may be through decreasing the expression of STAT1, which influences the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway that may inhibit apoptosis to relieve neurological impairment.

Effects of 2-Deoxyglucose on ischemic brain injuries in rats.

OBJECTIVES: In vivo and in vitro studies have shown that 2-deoxyglucose (2-DG) administration enhances tolerance and exerts neuroprotection against ischemic injury or oxidative stress. In this study, we investigated the effects of 2-DG on ischemic brain injuries in rats and determined whether the effects are related to sublethal endoplasmic reticulum (ER) stress. METHODS: 2-DG was administered systemically 7 d before the rats were subjected to focal cerebral ischemia (2 h) followed by reperfusion. Neurological score and infarct volume were evaluated, and protein expression of ER molecular chaperone glucose-regulated protein 78 (GRP78) and X-box protein-1 (XBP-1) was determined at different time points after reperfusion. RESULTS: 2-DG pretreatment significantly decreased neurological scores after reperfusion for 3 h, 6 h, 12 h, and 24 h, reduced infarct volume at 24 h after reperfusion compared to the corresponding control groups. ER molecular chaperone GRP78 and XBP-1 increased in 2-DG pretreatment group as compared to the control. CONCLUSION: Pretreatment with 2-DG improves the neurological function after cerebral ischemia-reperfusion injury. Increased expression of ER chaperone GRP78 and activation of XBP-1 may contribute to the protective effect of 2-DG against brain injury.

Tenecteplase Plus Butyphthalide for Stroke Within 4.5-6 Hours of Onset (EXIT-BT): a Phase 2 Study.

To date, the benefit of intravenous thrombolysis is confined to within 4.5 h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90 days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24 h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6 h of symptom onset selected using NCCT.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509).

Monosialoanglioside improves memory deficits and relieves oxidative stress in the hippocampus of rat model of Alzheimer's disease.

GM-1 ganglioside (GM-1) has been proposed as a new therapeutic agent against Alzheimer's disease (AD). Therefore, in this study we aimed to investigate the effects of GM1 on memory deficits and oxidative stress in the hippocampus of rat model of AD. Wistar rats were randomly divided into three groups (n = 15): control group, model group, and treatment group, which were injected with vehicle, Aß1-40, and Aß1-40 together with GM-1, respectively. Morris water maze test was performed to evaluate spatial learning and memory of the rats. Brain malondialdehyde (MDA) content was detected by biochemical assay, and 4-hydroxynonenal (4-HNE) level in the hippocampus was examined by immunohistochemistry. The results showed that learning and memory deficits were improved in treatment group compared to model group. Brain MDA content and 4-HNE level in hippocampus CA1 were much lower in treatment group than in model group. In summary, we demonstrate that GM-1 could improve spatial learning and memory deficits in rat model of AD, and this may be mediated by the inhibition of oxidative stress and lipid peroxidation in the neurons. These data suggest that GM-1 is a potential agent for AD treatment.

Prediction of early neurological deterioration in acute ischemic stroke patients treated with intravenous thrombolysis.

A proportion of acute ischemic stroke (AIS) patients suffer from early neurological deterioration (END) within 24 hours following intravenous thrombolysis (IVT), which greatly increases the risk of poor prognosis of these patients. Therefore, we aimed to explore the predictors of early neurological deterioration of ischemic origin (ENDi) in AIS patients after IVT and develop a nomogram prediction model. This study collected 244 AIS patients with post-thrombolysis ENDi as the derivation cohort and 155 patients as the validation cohort. To establish a nomogram prediction model, risk factors were identified by multivariate logistic regression analysis. The results showed that neutrophil to lymphocyte ratio (NLR) (OR 2.616, 95% CI 1.640-4.175, P < 0.001), mean platelet volume (MPV) (OR 3.334, 95% CI 1.351-8.299, P = 0.009), body mass index (BMI) (OR 1.979, 95% CI 1.285-3.048, P = 0.002) and atrial fibrillation (AF) (OR 8.012, 95% CI 1.341-47.873, P = 0.023) were significantly associated with ENDi. The area under the curve of the prediction model constructed from the above four factors was 0.981 (95% CI 0.961-1.000) and the calibration curve was close to the ideal diagonal line. Therefore, this nomogram prediction model exhibited good discrimination and calibration power and might be a reliable and easy-to-use tool to predict post-thrombolysis ENDi in AIS patients.

Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury.

Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms. Fingolimod (FTY-720) is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities, and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases. In the current research, the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model. Our results revealed that FTY-720 markedly decreased infarct volume, promoted neurological function recovery, and weakened the blood-brain barrier permeability of ischemic rats. The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels. These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.

Protective effects of oridonin against cerebral ischemia/reperfusion injury by inhibiting the NLRP3 inflammasome activation.

NOD-like receptor protein 3 (NLRP3) inflammasome is tightly related to the pathogenesis of cerebral ischemia/reperfusion (I/R) injury, and oridonin (Ori) has shown the potential to alleviate ischemia/reperfusion injury with underlying mechanisms. Our study aims to figure out whether Ori protects against the cerebral ischemia/reperfusion injury by the NLRP3 inflammasome signaling. In this study, a temporary middle cerebral artery occlusion (MCAO) and reperfusion surgery was conducted on male C57BL/6 mice to mimic cerebral I/R injury in vivo. Cellular model of cerebral I/R in vitro was achieved by oxygen-glucose deprivation and reintroduction (OGD/R) in BV2 microglia cells. We found that Ori treatment significantly relieved the neurological deficits, neuronal injury and microglia activation in I/R mice according to morphological and histological analyses. Meanwhile, the inactivation of NLRP3 inflammasome was determined in Ori-treated mice with significantly down-regulated expressions of inflammasome-related genes. Western-blot analysis further demonstrated the negative effect of Ori on NF-κB signaling with diminished phosphorylation and degradation of IκBα as well as suppressed translocation of p65. Furthermore, we indicated that Ori suppressed the activation of NLRP3 inflammasome in OGD/R induced BV2 microglia cells by inhibiting NF-κB signaling. In summary, our findings make Ori a potential candidate for therapy of cerebral I/R injury in the future.

Protective effect of 2-deoxy-D-glucose on the brain tissue in rat cerebral ischemia-reperfusion models by inhibiting Caspase-apoptotic pathway.

We observed the effect of 2-deoxy-D-glucose (2-DG) on the brain tissue in rat cerebral ischemia-reperfusion (I/R) and explored its mechanism. After observing the effect of 2-DG on endoplasmic reticulum stress (ERS), rats were randomly divided into sham-operation group, I/R group and I/R+2-DG group (each group with 60 rats). I/R models were prepared by middle cerebral artery occlusion. In I/R+2-DG group, each rat was given intraperitoneal 2-DG of 100 mg/kg once a day for 7 days before brain ischemia. According to different time points (3h, 6h, 12h, 24h and 48h) after I/R, each group was divided into 5 subgroups (each subgroup with 12 rats). Nerve cell apoptosis, and the expressions of mRNA and protein of glucose regulated protein 78 (GRP78), cleaved-caspase-9 and cleaved-caspase-3 were determined with TUNEL, Western blotting and RT-PCR, respectively, in rat cerebral hippocampal CA1 area at each time point. TUNEL-positive cells were significantly less in I/R+2-DG group than in I/R group at each time point (all P<0.01). In I/R and I/R+2-DG groups, the expressions of mRNA and protein of GRP78 reached the maximum 12 h after I/R, and cleaved-caspase-9 and cleaved-caspase-3 reached the maximum 24 h after I/R. Compared with sham-operation group, the expressions of mRNA and protein of GRP78, cleaved-caspase-9 and cleaved-caspase-3 were all significantly increased (all P<0.01) in I/R and I/R+2-DG groups. However, the expressions of mRNA and protein of GRP78 were significantly higher in I/R+2-DG group than in I/R group (all P<0.05), but the expressions of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3 were all significantly lower in I/R+2-DG group than in I/R group (all P<0.05). We conclude that 2-DG has a neuroprotective effect on the brain tissue in rat cerebral ischemia-reperfusion models. The mechanism may be that 2-DG starts ERS followed by up-regulation of mRNA and protein of GRP78 and down-regulation of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3, which blocks the apoptotic pathway.

Effects of erythropoietin combined with tissue plasminogen activator on the rats following cerebral ischemia and reperfusion.

OBJECTIVES: Exogenously administered recombinant human erythropoietin (rhEPO) has been reported to exhibit neuroprotective effects in animal models. However, there are still have some controversies that combination of EPO and tissue plasminogen activator (tPA) in acute ischemic stroke. In the present study, we investigated the effects of local intra-arterial infusion of low-dose EPO in combination with tPA on focal cerebral ischemic stroke. MATERIALS AND METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into five groups, including sham, vehicle, EPO, tPA, and EPO+tPA groups. Rats were subjected to middle cerebral artery occlusion (MCAO) and administrated with EPO (800 U/kg, middle cerebral artery injection), tPA (10 mg/kg, tail vein injection), EPO+tPA, or saline (vehicle) onset of reperfusion. Neurobehavioral deficits, infarct volume, brain edema, the expression of tight junction proteins (Claudin-5, Occludin), and AQP4 were assessed following 2 h ischemia and 24 h reperfusion. The number of apoptotic cells in the periinfarct region was detected by the terminal deoxyribonucleotide transferase dUTP nick end labeling (TUNEL) staining. RESULTS: The neurobehavioral deficits, brain infarct volume, edema volume, TUNEL-positive cells and downregulation of Claudin-5 and Occludin were alleviated by EPO or EPO plus tPA, following the ischemia/reperfusion (I/R) in rats. The EPO and EPO plus tPA both reduced the upregulation of AQP4 in the ischemic brain tissue. CONCLUSION: Our data demonstrate local intra-arterial infusion of low-dose EPO in combination with tPA protected against focal cerebral ischemia in rats manifested by a decrease in brain edema and blood-brain barrier (BBB) disruption after 2 h ischemia and 24 h reperfusion.

Significance of functional GRP78 polymorphisms in predicting the onset of type 2 diabetic peripheral neuropathy in Chinese population.

OBJECTIVE: The objective of this study is to investigate the significance of functional GRP78 polymorphisms in predicting the risk of type 2 diabetic peripheral neuropathy in Chinese population. METHODS: Between the years of 2006 and 2010, a total of 295 definitely diagnosed type 2 diabetes mellitus (T2DM) patients were included into our study cohort and followed for 3 years. At baseline and annual re-examinations, the patients underwent physical examinations, laboratory tests and evaluation of Michigan diabetic neuropathy score (MDNS). Age, gender, disease course, waist-hip circumference ratio (WHR), body mass index (BMI), triglycerine (TG), total cholesterol (Tch), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycosylated haemoglobin (HbA1c), uric acid elimination rate (UAER) and uric acid (UA) were recorded and GRP78 polymorphisms were tested by direct sequencing. The prognostic significance of GRP78 polymorphisms were analysed using monovariate and multivariate logistic regression. RESULTS: Three years after baseline, 32.9% (97/295) of the T2DM patients had suffered the development of diabetic peripheral neuropathy and GRP78 rs391957 promoter polymorphism is a significant risk factor for the onset of type 2 diabetic peripheral neuropathy. In monovariate regression model, the OR values of GRP78 rs391957 promoter polymorphism were 2.233 (C/T) and 2.734 (T/T). As for the model calibrated with demographic and laboratory indexes, the OR values were, respectively, 2.124 (C/T) and 2.423 (T/T). CONCLUSION: Our study suggested that the GRP78 rs391957 promoter polymorphism is a potential risk factor for type 2 diabetic peripheral neuropathy.

Effects of Ginkgo biloba extract on the apoptosis of oxygen and glucose-deprived SH-SY5Y cells and its mechanism.

OBJECTIVE: The aim was to observe the effects of the extract of Ginkgo biloba (EGb761) on the apoptosis of oxygen and glucose-deprived (OGD) human neuroblastoma cells (SH-SY5Y) cells and explore its mechanism. MATERIALS AND METHODS: SH-SY5Y cells were divided into normal control group, OGD group, OGD for 4 h and EGb761-pretreated groups including very low-concentration (20 µg/ml), low-concentration group (25 µg/ml), moderate-concentration group (50 µg/ml) and high-concentration group (100 µg/ml). Twenty four hours after reoxygenation, cell viability was determined with 3-[4, 5-dimehyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide assay, apoptosis rate was detected with annexin V-fluorescein isothiocyanate/propidium iodide double staining flow cytometry and the protein level of apoptosis-inducing factor (AIF) was observed with immunofluorescence technique in each group. RESULTS: Cell viability was significantly lower in OGD group than in EGb761-pretreated groups, especially in moderate-concentration group (50 µg/ml) (P < 0.005). Apoptosis rate was significantly lower in EGb761-pretreated groups than in OGD group (P < 0.001). Immunofluorescent staining showed that there was AIF nuclear translocation in both EGb761-pretreated groups and OGD group, but AIF nuclear translocation was less in EGb761-pretreated groups than in OGD group. CONCLUSION: EGb761 can reduce the apoptosis of OGD SH-SY5Y cells probably through inhibiting AIF nuclear translocation. This study provides a theoretical basis for the application of EGb761 in clinical practice.

Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion.

Local infusion of low dose erythropoietin (EPO) alleviates cerebral ischemia and reperfusion (I/R) injury in rats; however, the underlying molecular mechanisms are still unclear. The present study investigated the effect of low dose EPO treatment on I/R-induced endoplasmic reticulum (ER) stress in brain tissue and isolated microvessels in rodents. Sprague-Dawley rats were subjected to 2 h ischemia/24 h reperfusion by middle cerebral artery (MCA) occlusion, then administered fluorescein isothiocyanate-labeled EPO via MCA infusion (MCAI) or subcutaneous injection (SI) to compare the efficiency of two modes of delivery. Neurobehavioral deficits and infarct volume, and the expression of ER stress-associated proteins and apoptosis in brain tissue or isolated microvessels, as well as the transcriptional activity of 16 factors involved in ER stress and the unfolded protein response in brain tissue was asscessed. A higher EPO level in cerebrospinal fluid and brain tissue was observed in rats treated with EPO by MCAI (800 IU/kg) than by SI (5000 IU/kg). Moreover, neurobehavioral deficits and infarct volume were reduced in rats treated with EPO by MCAI and salubrinal. EPO suppressed the expression of ER stress signals glucose-regulated protein 78, activating transcription factor (ATF) 6α, and CCAAT enhancer-binding protein homologous protein (CHOP), as well as that of the pro-apoptotic protein caspase-3 in brain microvessels, and decreased the number of CHOP-positive, apoptotic neurons. EPO treatment also reduced the transcriptional activities of CHOP, forkhead box protein O1, and ATF4. These results provide evidence that low dose EPO treatment via MCAI provides neuroprotection following acute ischemic stroke by inhibiting the ER stress response.

[Clinical study on effect and therapeutical mechanism of composite Salvia injection on acute cerebral infarction].

OBJECTIVE: To investigate the curative effect and therapeutical mechanism of composite salvia injection (CSI) in treating ischemic cerebral infarction in the respect of oxygen free radical and apolipoprotein. METHODS: Sixty-eight cases of ischemic cerebral infarction within the first 72 hrs after onset were divided randomly into the CSI group (treated with CSI) and the control group (treated with Xueshuantong). Serum lipid peroxide (LPO) and superoxide dismutase (SOD) were measured by colorimetry and apolipoprotein A1 (ApoA1) and ApoB100 were measured with unidirectional immune diffusion method. RESULTS: Serum levels of LPO and ApoB100 were obviously lower, and levels of SOD and ApoA1 significantly higher in the CSI group than those in the control group (P < 0.05 or P < 0.01). The total effective rate of CSI in treating cerebral infarction was 88.24%, which was significantly higher than that of the control (P < 0.05). CONCLUSION: CSI shows definite effect in treating cerebral infarction, to reduce the oxygen free radical damage and regulate the apolipoprotein metabolism possibly was the important therapeutical mechanism.

Sex differences in health-related quality of life among adult stroke patients in Northeastern China.

Inconsistent results have been reported for the impact of sex on stroke outcomes. We investigated the differences in health-related quality of life between adult male and female stroke survivors in Northeastern China. Information on background variables was collected during hospital stay. Follow-up data were obtained through a phone interview 6 months after discharge, which included the Barthel Index and a 36-Item Short-Form Health Survey (SF-36) reflecting overall health status. The independent effects of sex on activities of daily living independence (Barthel Index ⩾ 95) were analyzed. Our results showed that female stroke patients were older than male stroke patients and were more likely to have transient ischemic attack and hypertension. Male stroke patients were more likely to have a history of smoking, heart disease and dyslipidemia, while female patients were less likely to achieve daily living independence. The mean scores of physical functioning, bodily pain, vitality, social functioning, emotional role, and mental health in the SF-36 survey were significantly higher in men than woman. Regression analyses confirmed that female sex was adversely associated with overall health status at discharge. In conclusion, our data demonstrated that there were sex differences in stroke recovery and quality of life among Chinese stroke survivors at 6 months post-discharge, with an overall worse stroke outcome for female stroke survivors.

Activation of T-LAK-cell-originated protein kinase-mediated antioxidation protects against focal cerebral ischemia-reperfusion injury.

T-LAK-cell-originated protein kinase (TOPK), a MAPKK-like kinase, is crucial for neural progenitor cell proliferation; however, the function of TOPK and the molecular mechanism underlying cerebral ischemia-reperfusion injury remains unknown. Therefore, we investigated the role of TOPK in experimental stroke. Sprague-Dawley rats underwent transient middle cerebral artery occlusion (tMCAO) and reperfusion, and TOPK small interfering RNA (siRNA) was delivered by intracerebroventricular injection at the beginning of MCAO. After TOPK overexpression and H2O2 stimulation in PC12 neuronal cells, antioxidative proteins, apoptosis-related proteins and signal pathways were detected by western blot analysis, the levels of the peroxidation products (malondialdehyde and 3-nitrotyrosine) were measured with ELISA. Phosphorylation of TOPK was increased in rat cortical neurons following tMCAO. TOPK overexpression in PC12 cells augmented levels of antioxidative proteins (peroxiredoxin 1 and 2, heme oxygenase 1 and manganese superoxide dismutase), as well as total superoxide dismutase activity, along with inhibition of malondialdehyde and 3-nitrotyrosine upon H2O2 stimulation. TOPK overexpression increased cell viability and reduced expression of caspase 3 and caspase 12 in PC12 cells in response to H2O2 . The p-ERK level was increased by TOPK overexpression, and antioxidative protection afforded by TOPK was abolished by blocking the extracellular signal-regulated kinase pathway in PC12 cells. TOPK siRNA increased the infarct volume and reduced total superoxide dismutase activity in the cortex in vivo after MCAO. These data reveal that activating TOPK confers neuroprotection against focal cerebral ischemia-reperfusion injury by antioxidative function, in part through activation of the extracellular signal-regulated kinase pathway.

Analysis on 85 case reports of adverse drug reactions.

This study investigated the occurrence and characteristics of adverse drug reactions (ADR) in our hospital and provide references for clinical rational drug use. We collected the 85 case reports of adverse drug reactions in our hospital in 2010 and made retrospective statistical analysis on them. The varieties of anti-infective drugs used are the most used. It also had the highest proportion of adverse drug reactions; the common symptom of adverse drug reactions is skin and accessory damage. Adverse drug reactions are affected by many factors, and relevant departments should strengthen ADR monitoring, to reduce or avoid the occurrence of adverse drug reactions.

Anti-inflammatory and anti-thrombogenic effects of atorvastatin in acute ischemic stroke.

Atorvastatin decreases inflammation and thrombogenesis in patients with carotid artery plaque. Atorvastatin is administered to lower lipid levels, but its anti-inflammatory and anti-thrombogenic effects remain unclear. Eighty-nine patients from northeastern China with acute ischemic stroke caused by large-artery atherosclerosis were randomly divided into the study and control groups. All patients received routine treatment, including antiplatelet therapy, circulatory support, and symptomatic treatment. The study group (n = 43) also received daily atorvastatin 20 mg/d, and the control group (n = 46) received daily placebo pills containing glucose. After 4 weeks, the levels of C-reactive protein, fibrinogen, and D-dimer were significantly lower in the study group than in the control group. Decreases in the levels of C-reactive protein, fibrinogen, and D-dimer were not associated with decreases in the levels of triacylglycerol and low-density lipoprotein cholesterol. These results suggest that atorvastatin reduces inflammation and thrombogenesis independent of its lipid-lowering effects in patients with acute ischemic stroke caused by large-artery atherosclerosis.