Clopidogrel with indobufen or aspirin in minor ischemic stroke or high-risk transient ischemic attack: a randomized controlled clinical study.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. OBJECTIVE: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. METHODS: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. RESULTS: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). CONCLUSION: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Medium-intensity statin with ezetimibe versus high-intensity statin in acute ischemic cerebrovascular disease (MESIA): A randomized clinical trial.

BACKGROUND: High-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. METHODS: We conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10-20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5-10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FINDINGS: This trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. INTERPRETATION: Compared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.

Object-centered family interactions for young autistic children: a diary study.

Autistic Children often struggle with social interaction and communication, studies have found that many of them prefer to interact with objects than people. However, there is a lack of research exploring the specific characteristics and factors involved in interactions within families with autistic children where objects are the center of the interaction. This paper describes the process and findings of a diary study exploring how young autistic children interact with their families through objects in natural scenarios. A one-week diary study was conducted with six families with young autistic children. Diary videos were recorded onsite and coded later according to a social interaction behavior scheme with corresponding diary entries. Qualitative data analysis was conducted to reveal possible patterns. Results revealed ongoing difficulties in establishing and maintaining family interaction and identified influential factors of object-centered family interaction. The most prevalent pattern observed was parents taking the lead in interactions, followed by the child's confirmation response. Remarkably, daily necessities emerged as potential physical mediums for enhancing family interactions, opening avenues for exploring tangible designs in human-computer interaction. These findings offer valuable implications for future research and the development of innovative designs that promote enriching interactions for autistic children and their families.

Plasma-induced nitrogen vacancy-mediated ammonia synthesis over a VN catalyst.

Plasma catalysis has recently been recognized as a promising route for artificial N2 reduction under mild conditions. Here we report a highly active VN catalyst for plasma-catalytic NH3 synthesis via the typical Mars-van Krevelen (MvK) mechanism. Our results indicate that NH3 synthesis occurs through the continuous regeneration and elimination of nitrogen vacancies on the VN surface. With this strategy, the VN catalyst achieves a superhigh NH3 yield of 143.2 mg h-1 gcat.-1 and a competitive energy efficiency of 1.43 gNH3 kW h-1.

Photocatalytic nitrogen fixation of metal-organic frameworks (MOFs) excited by ultraviolet light: insights into the nitrogen fixation mechanism of missing metal cluster or linker defects.

The vacancies of semiconductors have proven to be effective active sites for photocatalytic nitrogen fixation, but what about the role of defects in MOF materials? Herein, we report the first UiO-66 with photo-excited cluster defects and linker defects for photocatalytic nitrogen fixation. It was determined through the post-synthetic ligand exchange (PSE) process that the linker defects, rather than cluster defects, can greatly improve the performance, which is due to linker defects forming unsaturated metal nodes such as the vacancy in a semiconductor. Specifically, for photo-activated UiO-66, the NH4+ production rate was 196 and 68 µmol g-1 h-1 in air atmosphere under ultraviolet-visible (UV-Vis) and visible light, respectively. This report provides a new effective strategy to design efficient nitrogen fixation photocatalysts.

Effects of taillight shape on conspicuity of vehicles at night.

Taillight shape in a vehicle provides an essential lighting signal that enables the vehicle to be seen from the rear at night, thereby preventing rear-end crashes. This study aims to investigate the effects of taillight shape on vehicle conspicuity, and proposes ergonomic taillight shape solutions to vehicle designers and manufacturers. Two complementary experiments were conducted to examine three types of taillight shapes at three design levels. The first experiment was designed to investigate the detection speed of a driver and the fixation duration and fixation counts on leading vehicles with different taillight shapes, based on an eye-tracking methodology. The second experiment was designed to investigate the dynamic visual searching performance of a trailing driver for leading vehicles with different taillight shapes, based on a visual search task. The experimental results indicated that a long line-shaped taillight (striplight) was the optimal ergonomic solution for enhancing vehicle conspicuity. Vehicles with an enclosed contour-shaped taillight were more salient than those with an open contour-shaped taillight. Moreover, the experience and gender of the driver and the vehicle-observer distance were found to be closely related to vehicle conspicuity, and therefore, must be considered by vehicle designers when applying a specific taillight shape design. This study provides insights into the taillight shape design that not only aid vehicle designers or manufacturers in enhancing vehicle safety but also enable potential vehicle buyers to choose a safe lighting system.

In situ modification of cobalt on MXene/TiO2 as composite photocatalyst for efficient nitrogen fixation.

Modulation of the binding of the reactant or product species with catalysts is an effective approach to optimize the photocatalytic activity. Herein, we explored the relationship between the binding of reactant (N2) and product (NH3) with catalyst and the photocatalytic nitrogen fixation activity. The surface reactivity of nitrogen with water was tuned by introducing Co into the MXene@TiO2 catalysts, which the TiO2 nanoparticle derived from the in-situ growth on the surface of MXene nanosheets. Co modified adjusted the chemisorption equilibrium of the catalyst for reactant (N2) and product (NH3), thus promoted product desorption and efficiency of the active site. Remarkably, the optimal catalyst (MXene/TiO2/Co-0.5%) exhibited outstanding NH4+ production rate (110 µmol g-1 h-1) and excellent stability in pure water without any hole sacrificial agent under Ultraviolet-Visible (UV-vis) light in N2 and air ambient.

Transplantation of neural progenitor cells generated from human urine epithelial cell-derived induced pluripotent stem cells improves neurological functions in rats with stroke.

As a potentially unlimited autologous cell source, induced pluripotent stem cells (iPSCs) provide a needed option for the application of iPSC-derived neural progenitor cells (NPCs) for regenerative medicine for the treatment of stroke. To enable the application of iPSC technology, it is essential to develop a practical approach to generate iPSC cells under a non-viral, non-integration, feeder-free condition from the most optimal somatic cell type. In this study, we differentiated NPCs from a urine-derived iPSC line (UC-05) which was generated with optimized episomal vectors in a feeder-free culture system. UC-05 can be induced into NPCs efficiently in monolayer cultures using dual SMAD inhibitions, and have the ability to differentiate further into astrocytes and functional neurons in vitro. We then characterized UC-05-derived NPCs upon transplantation into the striatum of adult male rats subjected to transient middle cerebral artery occlusion (tMCAO) reperfusion. While NPCs were grafted into rats 7 days before the MCAO surgery, cells were found to migrate from the grafted side to the lesion side of the brain via corpus callosum 14 days after tMCAO. UC05-derived NPCs were grafted into the striatum 7 days after tMCAO, grafted cells can survive and differentiate into neurons and astrocytes 35 days after transplantation, and synaptic protein SYNAPSIN 1 could also be detected around the grafted human cells. tMCAO rats with NPC engraftment showed better behavior improvement in both postural reflex test and cylinder test compared to control rats engrafted with the cell medium only. Our data indicate that NPCs differentiated from urine-derived iPSCs could act similarly to endogenous neural progenitors in vitro and in vivo. Urine-derived iPSCs could be a potential candidate for cell transplantation therapy in stroke.

Circ_016719 plays a critical role in neuron cell apoptosis induced by I/R via targeting miR-29c/Map2k6.

BACKGROUND: Stroke is a leading cause of mortality worldwide. Rac-MAPK kinase 6 (Map2k6) plays important roles in cell proliferation and apoptosis. However, the role played by Map2k6 in stroke injury and the underlying mechanism of action remain unknown. METHODS: Mice received cerebral ischemia/reperfusion (I/R) injuries by transient middle cerebral artery occlusion. HT22 cells were subjected to oxygen glucose deprivation and reoxygenation (OGD/R) to simulate an I/R injury. Subsequently, the levels of circ_016719, miR-29c and Map2k6 expression were determined, and their interactions were examined by luciferase assays. Circ_016719 knockdown, miR-29c inhibition or Map2k6 overexpression was induced in HT22 cells; after which, the cells were examined for their viability, apoptosis, autophagy and proliferation, as well their levels of Map2k6, p38, p53, LC3B-I, LC3B-II, Beclin 1, and p62 expression. RESULTS: Significantly increased levels of circ_016719 and Map2k6, and decreased levels of miR-29c were observed in both in vivo and in vitro I/R injury models. In HT22 cells, circ_016719 knockdown significantly increased miR-29c expression and cell proliferation, but decreased Map2k6 expression and cell apoptosis. Additionally, significant increases in LC3B-I and p62 levels and decreased LC3B-II levels were observed, indicating that circ_016719 knockdown had significantly inhibited autophagy. Furthermore, additional inhibition of miR-29c markedly suppressed the effects of circ_016719 knockdown; however, that suppression was significantly attenuated by Map2k6 overexpression. Additionally, Map2k6 was identified as a direct target of miR-29c, which in turn, might be sponged by circ_016719. CONCLUSIONS: Our results suggest that circ_016719 directly targets miR-29c, and thereby regulates the expression and functions of Map2k6, which significantly contributes to the pro-apoptotic role of circ_016719.

Eicosapentaenoic acid prevents inflammation induced by acute cerebral infarction through inhibition of NLRP3 inflammasome activation.

OBJECTIVE: Acute cerebral infarction (ACI) is the most common type of acute cerebrovascular diseases resulting in high rate of death and disability. Numerous evidences show that inflammation is the leading cause of ischemic brain injury, thus anti-inflammatory therapy is an attractive candidate for ischemic brain damage. Eicosapentaenoic acid (EPA) exerts anti-inflammatory activity in lots of human inflammatory diseases, whereas its effect in ACI is left to elucidate. METHOD: Nlpr3-/- mice, Gpr40-/-; Gpr120-/- mice and mice with right middle cerebral artery occlusion (MCAO) were used to detect NLR family pyrin domain containing 3 (NLRP3) inflammasome activation by Western Blot and the release of proinflammatory cytokines by ELISA. To estimate the acute ischemic condition in vitro, oxygen-glucose deprivation (OGD) was induced in BV2 microglia cells. Transfection of the shRNA targeting GPR40 and GPR120 mRNA into BV2 cells was also assessed. Apoptosis in ischemic cerebral tissues and BV2 cells was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry. RESULT: Here we show that EPA suppresses ACI-induced inflammatory responses through blocking NLRP3 inflammasome activation. In addition, EPA inhibits NLRP3 inflammasome activation through G protein-coupled receptor 40 (GPR40) and GPR120. Importantly, EPA ameliorates ACI-induced apoptosis. CONCLUSION: EPA exerts beneficial effect on ACI-induced inflammation through blocking NLRP3 inflammasome activation by GPR40 and GPR120. Our findings suggest the potential clinical use of EPA in ACI.

MOF-Derived Co3O4@NC with Core-Shell Structures for N2 Electrochemical Reduction under Ambient Conditions.

We report the development of MOF-derived nitrogen-doped carbon/Co3O4 nanocomposites (Co3O4@NCs) with core-shell structures as an efficient electrocatalyst for the artificial nitrogen fixation at room temperature and atmospheric pressure in 0.05 M H2SO4. It exhibits a high NH3 yield of 42.58 µg h-1 mgcat.-1 and a faradaic efficiency of 8.5% at -0.2 V versus reversible hydrogen electrode. Experimental results show that the great N2 reduction reaction performance of Co3O4@NCs originates from the synergistic effects of N-doped carbon and Co3O4 with significant oxygen vacancy. In addition, we speculate that the core-shell structure can further enhance the electrochemical activity for producing NH3.

Connectivity map identifies luteolin as a treatment option of ischemic stroke by inhibiting MMP9 and activation of the PI3K/Akt signaling pathway.

This study aimed to explore potential new drugs in the treatment of ischemic stroke by Connectivity Map (CMap) and to determine the role of luteolin on ischemic stroke according to its effects on matrix metalloproteinase-9 (MMP9) and PI3K/Akt signaling pathway. Based on published gene expression data, differentially expressed genes were obtained by microarray analysis. Potential compounds for ischemic stroke therapy were obtained by CMap analysis. Cytoscape and gene set enrichment analysis (GSEA) were used to discover signaling pathways connected to ischemic stroke. Cell apoptosis and viability were, respectively, evaluated by flow cytometry and an MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were used to test the expression of MMP9 and the PI3K/Akt signaling pathway-related proteins in human brain microvascular endothelial cells (HBMECs) and tissues. Additionally, the infarct volume after middle cerebral artery occlusion (MCAO) was determined by a TTC (2,3,5-triphenyltetrazolium chloride) assay. The microarray and CMap analyses identified luteolin as a promising compound for future therapies for ischemic stroke. Cytoscape and GSEA showed that the PI3K/Akt signaling pathway was crucial in ischemic stroke. Cell experiments revealed that luteolin enhanced cell viability and downregulated apoptosis via inhibiting MMP9 and activating the PI3K/Akt signaling pathway. Experiments performed in vivo also demonstrated that luteolin reduced the infarct volume. These results suggest that luteolin has potential in the treatment of ischemic stroke through inhibiting MMP9 and activating PI3K/Akt signaling pathway.

Chronic colitis induces meninges traffic of gut-derived T cells, unbalances M1 and M2 microglia/macrophage and increases ischemic brain injury in mice.

Ischemic stroke is one of the most common diseases leading to death and is the primary cause of physical handicap. Recent studies have reported that chronic colitis increases the risk of ischemic stroke, but it is unknown whether chronic colitis participates in ischemic brain injury directly. A combined mouse model of chronic colitis induced by dextran sodium sulfate (DSS) and ischemic stroke induced by photochemical infarction was used in this study. We demonstrated that chronic colitis significantly increased the infarction volume, activated microglia/macrophage numbers, proliferation of M1 microglia/macrophage, non-gut-derived CD4+ T lymphocyte penetration and decreased neuron numbers in the peri-infarction at 7 d after stroke. Furthermore, gut-derived CD4+ T cell accumulation on the meninges was observed at 7 d after stroke. In addition, selective depletion of meningeal macrophages resulted in a reduction of infarction volume and the non-gut-derived CD4+ T lymphocyte penetration. We concluded that chronic colitis exacerbated ischemic stroke by promoting CD4+ T cell migration from the gut to the meninges and disequilibrium of M1 and M2 microglia/macrophages. We speculated that the gut-derived CD4+ T cells may interact with meningeal macrophages and result in non-gut-derived CD4+ T lymphocyte infiltration that aggravated brain injury in ischemic stroke.

Vagus Nerve Stimulation Attenuates Cerebral Microinfarct and Colitis-induced Cerebral Microinfarct Aggravation in Mice.

Cerebral cortical microinfarct (CMI) is common in patients with dementia and cognitive decline. Emerging studies reported that intestinal dysfunction influenced the outcome of ischemic stroke and that vagus nerve stimulation (VNS) protected against ischemic stroke. However, the effects of intestinal dysfunction and VNS on CMI are not clear. Therefore, we examined the influence of colitis and VNS on CMI and the mechanisms of VNS attenuating CMI in mice with colitis. CMI was induced using a two-photon laser. Colitis was induced using oral dextran sodium sulfate (DSS). The cervical vagus nerve was stimulated using a constant current. In vivo blood-brain barrier (BBB) permeability was evaluated using two-photon imaging. Infarct volume, microglial and astrocyte activation, oxidative stress and proinflammatory cytokine levels were assessed using immunofluorescent and immunohistochemical staining. The BBB permeability, infarct volume, activation of microglia and astrocytes and oxidative stress increased significantly in mice with colitis and CMI compared to those in mice with CMI. However, these processes were reduced in CMI mice when VNS was performed. Brain lesions in mice with colitis and CMI were significantly ameliorated when VNS was performed during the acute phase of colitis. Our study demonstrated that VNS alleviated CMI and this neuroprotection was associated with the suppression of BBB permeability, neuroinflammation and oxidative stress. Also, our results indicated that VNS reduced colitis-induced microstroke aggravation.

Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

BACKGROUND AND OBJECTIVES: Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. MATERIALS AND METHODS: 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. RESULTS: Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. CONCLUSION: Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment.

Real time relationship between individual finger force and grip exertion on distal phalanges in linear force following tasks.

Individual finger force (FF) in a grip task is a vital concern in rehabilitation engineering and precise control of manipulators because disorders in any of the fingers will affect the stability or accuracy of the grip force (GF). To understand the functions of each finger in a dynamic grip exertion task, a GF following experiment with four individual fingers without thumb was designed. This study obtained four individual FFs from the distal phalanges with a cylindrical handle in dynamic GF following tasks. Ten healthy male subjects with similar hand sizes participated in the four-finger linear GF following tasks at different submaximal voluntary contraction (SMVC) levels. The total GF, individual FF, finger force contribution, and following error were subsequently calculated and analyzed. The statistics indicated the following: 1) the accuracy and stability of GF at low %MVC were significantly higher than those at high SMVC; 2) at low SMVC, the ability of the fingers to increase the GF was better than the ability to reduce it, but it was contrary at high SMVC; 3) when the target wave (TW) was changing, all four fingers strongly participated in the force exertion, but the participation of the little finger decreased significantly when TW remained stable; 4) the index finger and ring finger had a complementary relationship and played a vital role in the adjustment and control of GF. The middle finger and little finger had a minor influence on the force control and adjustment. In conclusion, each of the fingers had different functions in a GF following task. These findings can be used in the assessment of finger injury rehabilitation and for algorithms of precise control.

Ischemic stroke damages the intestinal mucosa and induces alteration of the intestinal lymphocytes and CCL19 mRNA in rats.

The immunoreaction has a pivotal effect on ischemic stroke. It has been demonstrated that intestinal lymphocytes infiltrate into the brain and aggravate tissue injury after stroke. However, less attention has been paid to the influence on the intestinal immunology as well as morphology. Here, we utilized a rat permanent middle cerebral artery occlusion (MCAO) model to investigate the influences on intestinal mucosa, lymphocytes of the gut-associated lymphoid tissue (GALT), and the intestinal expression of CCL25 mRNA and CCL19 mRNA of stroke. Rats were randomly divided into stroke, sham, and control groups. Stroke and sham groups were further divided into interval groups of 6h, 12h, and 24h after surgery. Intestinal pathophysiological changes were observed by hematoxylin-eosin (H&E) staining. The lymphocyte numbers were detected by flow cytometry. The expression of CCL25 mRNA and CCL19 mRNA was tested with the PCR technique. We found significant necrosis and shedding of the epithelium after stroke. Moreover, the lesion aggravated with time. In addition, there was a significant increase of T lymphocytes in Peyer's patches (PPs), especially at 12h and 24h after stroke, while no differences in the number of B lymphocytes and the intraepithelial lymphocytes (IELs) were found. The data displayed no alteration of CCL25 mRNA expression. In contrast, an upregulation of CCL19 mRNA expression was detected at 6h after stroke. This study showed that ischemic stroke significantly damaged the intestinal epithelium and activated intestinal immunity.

Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats.

Glial cell line-derived neurotrophic factor (GDNF) is a potential therapeutic protein on a variety of central nervous system diseases including ischemic stroke. However, GDNF is a large molecule that cannot cross the blood-brain barrier (BBB), which is still intact in the early hours after stroke when neural rescue is possible. PEP-1 protein transduction domain can deliver protein cargo across the cell membrane and the BBB. In the present study, we generated a novel fusion protein PEP-1-GDNF and examined whether PEP-1-GDNF is protective in focal cerebral ischemia. PEP-1-GDNF (200 µg/kg) or PBS was intravenously applied over 5 min immediately after reperfusion of 90 min transient middle cerebral artery occlusion (MCAO). After 28 days, rats were deeply anesthetized and decapitated. Behavioral tests were performed during this period. The results showed that PEP-1-GDNF significantly reduced the infarct volume and improved behavioral function. Further, PEP-1-GDNF promoted the cell proliferation and differentiation in the dentate gyrus of the hippocampus and attenuated ischemia-induced learning and memory damage.

Persistent pseudobulbar affect secondary to acute disseminated encephalomyelitis.

Pseudobulbar affect (PBA) is a common complication of central nervous system diseases such as stroke, multiple sclerosis, and other neurological diseases, but it remains under-recognized and under-treated in the clinic. PBA caused by acute disseminated encephalomyelitis (ADEM) has rarely been reported. Here, we report a 30-year-old Chinese woman who has experienced PBA from ADEM for 7 years. The patient's principal manifestations were extreme emotions or tears when she saw, heard, or spoke about sad news or other sad things; the durations of these unmanageable emotions were often less than 30 sec, and they occurred at frequencies that ranged from one to several times a day. Occasionally, she laughed uncontrollably while people were talking despite a lack of funny or sad stimuli in the conversation or the surrounding environment. Thus, her social functioning was impaired. This case indicates that the long-term PBA can occur secondarily to ADEM, and this possibility should be considered clinically to ensure timely identification and treatment.