Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

Enhancing cancer therapy: The role of drug delivery systems in STAT3 inhibitor efficacy and safety.

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment.

SIRT1 regulates mitochondrial fission to alleviate high altitude hypoxia inducedcardiac dysfunction in rats via the PGC-1α-DRP1/FIS1/MFF pathway.

High-altitude exposure has been linked to cardiac dysfunction. Silent information regulator factor 2-related enzyme 1 (sirtuin 1, SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, plays a crucial role in regulating numerous cardiovascular diseases. However, the relationship between SIRT1 and cardiac dysfunction induced by hypobaric hypoxia (HH) remains unexplored. This study aims to assess the impact of SIRT1 on HH-induced cardiac dysfunction and delve into the underlying mechanisms, both in vivo and in vitro. In this study, we have demonstrated that exposure to HH results in cardiomyocyte injury, along with the downregulation of SIRT1 and mitochondrial dysfunction. Upregulating SIRT1 significantly inhibits mitochondrial fission, improves mitochondrial function, reduces cardiomyocyte injury, and consequently enhances cardiac function in HH-exposed rats. Additionally, HH exposure triggers aberrant expression of mitochondrial fission-regulated proteins, with a decrease in PPARγ coactivator 1 alpha (PGC-1α) and mitochondrial fission factor (MFF) and an increase in mitochondrial fission 1 (FIS1) and dynamin-related protein 1 (DRP1), all of which are mitigated by SIRT1 upregulation. Furthermore, inhibiting PGC-1α diminishes the positive effects of SIRT1 regulation on the expression of DRP1, MFF, and FIS1, as well as mitochondrial fission. These findings demonstrate that SIRT1 alleviates HHinduced cardiac dysfunction by preventing mitochondrial fission through the PGC-1α-DRP1/FIS1/MFF pathway.

Metabolomics-Based Effects of a Natural Product on Remyelination After Cerebral Ischemia Injury Via GABABR-pCREB-BDNF Pathway.

BACKGROUND: Yi-Qi-Tong-Luo Granules (YQTLs) is a natural compound of Traditional Chinese Medicine authorized by China Food and Drug Administration (CFDA). These granules are employed in the convalescent stage of cerebral infarction and render notable clinical efficacy. This study aims to uncover the underlying mechanisms of YQTLs on remyelination after cerebral ischemia injury. MATERIALS AND METHODS: We established cerebral ischemia model in rats using microsphere-induced multiple cerebral infarction (MCI). We evaluated the pharmacological effects of YQTLs on MCI rats, through Morri's water maze test, open field test, hematoxylin and eosin staining, and glycine silver immersion. We employed liquid chromatography mass spectrometry metabolomics to identify differential metabolites. Enzyme-linked immunosorbent assay was utilized to measure the release of neurotrophins, while immunofluorescence staining was used to assess oligodendrocyte precursor cells differences and myelin regeneration. We used Western blotting to validate the protein expression of remyelination-associated signaling pathways. RESULTS: YQTLs significantly improves cognitive function following cerebral ischemia injury. Pathological tissue staining revealed that YQTLs administration inhibits neuronal denaturation and neurofibrillary tangles. We identified 141 differential metabolites among the sham, MCI, and YQTLs-treated MCI groups. Among these metabolites, neurotransmitters were identified, and notably, gamma-aminobutyric acid (GABA) showed marked improvement in the YQTLs group. The induction of neurotrophins, such as brain-derived neurotrophic factor (BDNF) and PDGFAA, upregulation of olig2 and MBP expression, and promotion of remyelination were evident in YQTLs-treated MCI groups. Gamma-aminobutyric acid B receptors (GABABR), pERK/extracellular regulated MAP kinase, pAKT/protein kinase B, and pCREB/cAMP response element-binding were upregulated following YQTLs treatment. CONCLUSION: YQTLs enhance the binding of GABA to GABABR, thereby activating the pCREB/BDNF signaling pathway, which in turn increases the expression of downstream myelin-associated proteins and promotes remyelination and cognitive function.

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors.

Immunotherapy has emerged as a potent strategy in cancer treatment, with many approved drugs and modalities in the development stages. Despite its promise, immunotherapy is not without its limitations, including side effects and suboptimal efficacy. Using nanoparticles (NPs) as delivery vehicles to target immunotherapy to lymph nodes (LNs) can improve the efficacy of immunotherapy drugs and reduce side effects in patients. In this context, this paper reviews the development of LN-targeted immunotherapeutic NP strategies, the mechanisms of NP transport during LN targeting, and their related biosafety risks. NP targeting of LNs involves either passive targeting, influenced by NP physical properties, or active targeting, facilitated by affinity ligands on NP surfaces, while alternative methods, such as intranodal injection and high endothelial venule (HEV) targeting, have uncertain clinical applicability and require further research and validation. LN targeting of NPs for immunotherapy can reduce side effects and increase biocompatibility, but risks such as toxicity, organ accumulation, and oxidative stress remain, although strategies such as biodegradable biomacromolecules, polyethylene glycol (PEG) coating, and impurity addition can mitigate these risks. Additionally, this work concludes with a future-oriented discussion, offering critical insights into the field.

Seizing the fate of lymph nodes in immunotherapy: To preserve or not?

Lymph node dissection has been a long-standing diagnostic and therapeutic strategy for metastatic cancers. However, questions over myriad related complications and survival outcomes are continuously debated. Immunotherapy, particularly neoadjuvant immunotherapy, has revolutionized the conventional paradigm of cancer treatment, yet has benefited only a fraction of patients. Emerging evidence has unveiled the role of lymph nodes as pivotal responders to immunotherapy, whose absence may contribute to drastic impairment in treatment efficacy, again posing challenges over excessive lymph node dissection. Hence, centering around this theme, we concentrate on the mechanisms of immune activation in lymph nodes and provide an overview of minimally invasive lymph node metastasis diagnosis, current best practices for activating lymph nodes, and the prognostic outcomes of omitting lymph node dissection. In particular, we discuss the potential for future comprehensive cancer treatment with effective activation of immunotherapy driven by lymph node preservation and highlight the challenges ahead to achieve this goal.

The glymphatic system: a new perspective on brain diseases.

The glymphatic system is a brain-wide perivascular pathway driven by aquaporin-4 on the endfeet of astrocytes, which can deliver nutrients and active substances to the brain parenchyma through periarterial cerebrospinal fluid (CSF) influx pathway and remove metabolic wastes through perivenous clearance routes. This paper summarizes the composition, overall fluid flow, solute transport, related diseases, affecting factors, and preclinical research methods of the glymphatic system. In doing so, we aim to provide direction and reference for more relevant researchers in the future.

Faster velocity changes in the near-surface soil freeze state in croplands than in forests across northeast China from 1979 to 2020.

Climate warming has significantly changed the near-surface soil freeze state, significantly impacting terrestrial ecosystems and regional agroforestry production. As Northeast China (NEC) is highly sensitive to climate change, this study introduces the concept of velocity to analyze the spatial pattern of frozen days (FDAY), onset date of soil freeze (FON), offset date of soil freeze (FOFF), and number of soil freeze/thaw cycles in spring (FTC) in NEC from 1979 to 2020. We observed that the velocity changes of FDAY, FON, and FTC in croplands were significantly higher than those in forests (difference >1 km yr-1), with the fastest velocity changes found in the cropland of the Songnen Plain. The highest velocity of FOFF was found in the forests of the Greater Khingan Range. In most study areas (>60%), the isoline of FDAY/FON/FOFF/FTC showed a northward movement. The isoline of FDAY/FON/FOFF/FTC moved in the cold direction in each cropland region (Sanjiang, Songnen, and Liaohe River Plains) and forest regions (Greater Khingan and Lesser Khingan Ranges, and the Changbai Mountains). The results of the quantitative analysis indicate that air temperature (TA) had a more significant effect on the velocity change of FDAY and FON in cropland, whereas snowpack is the dominant factor in forests. In both forests and croplands, the main factor affecting the velocity of FOFF was snowpack, and TA mainly affected the FTC. This study is significant for formulating regional climate change countermeasures and maintaining ecological security in cold regions.

Panax notoginseng Saponins Stimulates Neurogenesis and Neurological Restoration After Microsphere-Induced Cerebral Embolism in Rats Partially Via mTOR Signaling.

P. Notoginseng Saponins (PNS), the main active component of herbal medicine Panax notoginseng, has been widely used to treat cerebrovascular diseases. It has been acknowledged that PNS exerted protection on nerve injuries induced by ischemic stroke, however, the long-term impacts of PNS on the restoration of neurological defects and neuroregeneration after stroke have not been thoroughly studied and the underlying molecular mechanism of stimulating neurogenesis is difficult to precisely clarify, much more in-depth researches are badly needed. In the present study, cerebral ischemia injury was induced by microsphere embolism (ME) in rats. After 14 days, PNS administration relieved cerebral ischemia injury as evidenced by alleviating neurological deficits and reducing hippocampal pathological damage. What's more, PNS stimulated hippocampal neurogenesis by promoting cell proliferation, migration and differentiation activity and modulated synaptic plasticity. Increased number of BrdU/Nestin, BrdU/DCX and NeuroD1-positive cells and upregulated synapse-related GAP43, SYP, and PSD95 expression were observed in the hippocampus. We hypothesized that upregulation of brain-derived neurotrophic factor (BDNF) expression and activation of Akt/mTOR/p70S6K signaling after ME could partially underlie the neuroprotective effects of PNS against cerebral ischemia injury. Our findings offer some new viewpoints into the beneficial roles of PNS against ischemic stroke.

[Resveratrol attenuates cardiac function impairment in plateau hypobaric hypoxia rats].

Objective: To study the protective effects of resveratrol (RSV) on cardiac function in rats with high altitude hypobaric hypoxia and its mechanisms. Methods: Thirty-six rats were randomly divided into control group, hypobaric hypoxia group (HH) and hypobaric hypoxia + RSV group (HH+RSV) according to the random number, 12 rats in each group. Rats in the HH and HH+RSV groups were subjected to chronic long-term high altitude hypobaric hypoxia intervention for 8 weeks in a hypobaric chamber at a simulated altitude of 6 000 m for 20 h / d. The rats of HH + RSV were fed with RSV at a dose of 400 mg/(kg·d). The rats were tested once a week for body weight and twice a week for food intake. Before execution, the rats were tested by blood cell analyzer for routine blood parameters and echocardiogram for cardiac function parameters in each group. The routine blood indexes of each group were measured by blood cell analyzer, the cardiac function indexes of each group were measured by echocardiography, myocardial hypertrophy was evaluated by HE staining, myocardial tissue reactive oxygen levels were evaluated by dihydroethidium (DHE) staining. Oxidative stress was evaluated by serum and myocardial tissue total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD) and malondialdehyde (MDA) content. Results: Compared with the C group, the body mass and food intake of rats were decreased significantly (P＜0.05) in HH group, while compared with the C group, RSV had no significant effects on the body mass and food intake of rats in the HH+RSV group (P＞0.05). Compared with the C group, the levels of erythrocytes and hemoglobin of rats in the HH group were increased significantly (P＜0.05), while the platelet concentration was decreased significantly(P＜0.05); compared with the HH group, the erythrocyte and hemoglobin levels were decreased significantly (P＜0.05) and platelet concentration was increased significantly(P＜0.05) in rats of the HH+RSV group. Compared with the C group, the cardiac coefficient, myocardial fiber diameter and thickness were significantly increased in the HH group (P＜0.05); compared with the HH group, the cardiac coefficient and myocardial fiber thickness were significantly decreased in the HH+RSV group (P＜0.05). Echocardiographic analysis showed a significant increase in ventricular wall thickness (P＜0.05) and a significant decrease in ejection fraction and cardiac output (P＜0.05) in the HH group compared with the C group, and a significant decrease in ventricular wall thickness and a significant improvement in cardiac function (P＜0.05) in the HH+RSV group compared with the HH group. The results of DHE staining showed that myocardial tissue reactive oxygen levels were increased significantly in the HH group compared with the C group (P＜0.05); myocardial tissue reactive oxygen levels were significantly restored in the HH+RSV group compared with the HH group (P＜0.05). The oxidative/antioxidant results showed that the serum and myocardial T-AOC and SOD activities were decreased significantly (P＜0.05) and the MDA level was increased significantly (P＜0.05) in the HH group compared with the C group; the serum and myocardial T-AOC and SOD activities were increased significantly (P＜0.05) and the MDA level was decreased significantly(P＜0.05) in the HH+RSV group compared with the HH group. Conclusion: Long-term plateau hypobaric hypoxia exposure leads to myocardial hypertrophy and reduced cardiac function in rats. Resveratrol intervention significantly improves myocardial hypertrophy and cardiac function in rats caused by altitude hypobaric hypoxia exposure, which is closely related to reducing of reactive oxygen species and improving myocardial oxidative stress levels.

Histochemistry of microinfarcts in the mouse brain after injection of fluorescent microspheres into the common carotid artery.

The mouse model of multiple cerebral infarctions, established by injecting fluorescent microspheres into the common carotid artery, is a recent development in animal models of cerebral ischemia. To investigate its effectiveness, mouse models of cerebral infarction were created by injecting fluorescent microspheres, 45-53 µm in diameter, into the common carotid artery. Six hours after modeling, fluorescent microspheres were observed directly through a fluorescence stereomicroscope, both on the brain surface and in brain sections. Changes in blood vessels, neurons and glial cells associated with microinfarcts were examined using fluorescence histochemistry and immunohistochemistry. The microspheres were distributed mainly in the cerebral cortex, striatum and hippocampus ipsilateral to the side of injection. Microinfarcts were found in the brain regions where the fluorescent microspheres were present. Here the lodged microspheres induced vascular and neuronal injury and the activation of astroglia and microglia. These histopathological changes indicate that this animal model of multiple cerebral infarctions effectively simulates the changes of various cell types observed in multifocal microinfarcts. This model is an effective, additional tool to study the pathogenesis of ischemic stroke and could be used to evaluate therapeutic interventions. This study was approved by the Animal Ethics Committee of the Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences (approval No. D2021-03-16-1) on March 16, 2021.

Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway-Dependent Cerebral Microvascular Protection.

Stroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia model in rats by MCAO and used SLT (33 and 16.5 mg/kg) to intervene. The results showed SLT dose dependently decreased infarction volumes, relieved neuron degeneration and loss, and ameliorated neurological functions, and the dose of 33 mg/kg had statistical significance (compared with the model group, p < 0.05); SLT of 33 mg/kg also significantly inhibited the elevation in brain water content and the loss in claudin-1 and occludin expressions; additionally, it significantly increased nucleus translocation of Nrf2, elevated the expression of HO-1, and raised the activity of SOD and content of GSH (compared with the model group, p < 0.05 or 0.01). These results testified SLT's anti-brain ischemia effect and hint this effect may be related to the protection of brain microvascular endothelial cells (BMECs) that is dependent on the Nrf2 pathway. To further testify, we cultured hCMEC/D3 cells, duplicated OGD/R model to simulate ischemia, and used SLT (3.125, 6.25, and 12.5 mg/L) to treat. SLT dose dependently and significantly inhibited the drop in cell viabilities, and activated the Nrf2 pathway by facilitating Nrf2 nucleus translocation, and increasing HO-1 expression, SOD activity, and GSH content (compared with the model group, p < 0.05 or 0.01); last, the anti-OGD/R effects of SLT, including raising cell viabilities, inhibiting the elevation in dextran permeability, and preserving expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. The in vitro experiment undoubtedly confirmed the direct protective effect of SLT on BMECs and the obligatory role of the Nrf2 pathway in it. Collectively, data of this study suggest that SLT's therapeutic effect on brain ischemia is related to its Nrf2-dependent BMECs protection.

Electrochemical oxidation of methyl orange by a Magnéli phase Ti4O7 anode.

In this study, high quality Magnéli phase Ti4O7 bulks with electrical conductivity up to 961.5 S cm-1 were successfully prepared by spark plasma sintering (SPS) and then served as electrode materials for electrochemical oxidation of azo dye methyl orange (MO). The influences of current density and initial dye concentration on the removal rates of MO and chemical oxygen demand (COD) were studied. Removal of MO and COD exhibited an increase with increasing current density and decreasing initial concentration of MO. Complete removal of MO was realized within a short time under all experimental conditions. The removal rate of COD reached 91.7% when current density was 10 mA cm-2 and initial dye concentration was 100 mg L-1. In addition, the electrochemical oxidation rate could be described through a pseudo-first-order kinetic constant k, and the obtained experimental results could be well fitted with a proposed kinetic model in all the examined conditions. Possible degradation mechanisms for electrochemical oxidation of MO by Ti4O7 electrode were proposed on the basis of intermediate products analysis. Tests were also conducted with other commercial electrodes for comparison, including commercial graphite, stainless-steel and dimension stable anode (DSA) electrodes. The results showed that Ti4O7 anode exhibited the fastest electrochemical oxidation rates than those of the other electrodes. This study provides a feasible method for realizing high efficiency of electrochemical oxidation degradation by Ti4O7 electrode.

[Characterization and pathophysiological changes of cerebral infarction rat model with qi-deficiency and blood-stasis Syndrome].

This study aimed to observe the general state and changes in pathophysiological indexes of multiple cerebral infarction rat model with Qi-deficienty and Blood-stasis syndrome. Rats were randomly divided into 4 groups(with 30 in each group): the normal group, the sham group, the model group and the Yiqi Huoxue recipe group. Rats in the model group and Yiqi Huoxue group were provided with interruptable sleep deprivation for 7 days before the multiple cerebral infarction operation, and followed by another 4 weeks of sleep deprivation; rats in the Yiqi Huoxue group were intragastrically administrated with drug at a dose of 26 g·kg⁻¹, once a day for 4 weeks. The general state was observed, and the pathophysiological indexes were measured at 48 h, 2 weeks and 4 weeks after administration. The results showed that rats in the normal group and the sham group represented a good general state and behaviors, with a normal morphological structure of brain tissues; rats in the model group featured yellow fur, depression, accidie, loose stools and movement disorder, with obvious brain histomorphological damage, which became aggravated with the increase of modeling time; rats in the Yiqi Huoxue group showed release in the general state and above indexes. Compared with the sham group at three time points, rats in the model group showed decrease in body weight, exhaustive swimming time and RGB value of tongue surface image, and increase in whole blood viscosity of the shear rate under 5, 60 and 150 S⁻¹, reduction in cerebral cortex Na⁺-K⁺-ATPase, Ca²âº-ATPase activity and contents of 5-HT, rise in TXB2 levels and decline in 6-keto-PGF1a in serum(P<0.05, P<0.01). Compared with the model group, rats in the Yiqi Huoxue group showed alleviations in the above indexes at 2 w and 4 w(P<0.05, P<0.01). The results showed that the characterization and pathophysiological indexes in the multiple cerebral infarction rat model with Qi-deficiency and blood-stasis syndrome were deteriorated; Yiqi Huoxue recipe could significantly alliviate the abnormal conditions, which suggested of the model was stable and reliable and the pathophysiologic evolutionary mechanism might be related to energy metabolism dysfunction, vasoactive substance abnormality and changes in neurotransmitters.

Attractive and repulsive contributions of localized excitability inhomogeneities and elimination of spiral waves in excitable media.

The attracting and repelling of spiral waves in a two-dimensional excitable medium in the presence of localized excitability inhomogeneities are studied. The choice of two effects depends on the comparison of excitabilities inside and outside the localized obstacle. We inspect the changes in attracting and repelling behaviors with respect to the size of the obstacle and the initial distance between the center of the spiral core and the obstacle. To understand the occurrence of these phenomena, we investigated the small v-value areas near the tip and the function of the wave velocity as the excitability parameter ε. Considering the attributes of the attractive obstacle, an eliminating scheme of spiral waves is proposed in which the attractive obstacle is rapidly moved at several fixed times. This method can avoid the high-amplitude and high-frequency stimulus in most conventional methods.

[Effect of sailuotong capsule on intervening cognitive dysfunction of multi-infarct dementia in rats].

OBJECTIVE: To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism. METHOD: All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues. RESULT: Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01). CONCLUSION: Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues.

[Effect of sailuotong capsule on Glu and GABA levels as well as NMDA receptor subtypes expression in recovery period of rat multiple cerebral infarction].

The rat model of multi-infarct was adopted in this study to elucidate the protective mechanism of Sailuotong capsule (Sailuotong) in recovery period of multiple cerebral infarction. The effects of Sailuotong on levels of Glu, GABA and the expression of NMDA receptor subtypes including NR1, NR2A and NR2B, were detected. The multi-infarct model rats were established by injecting embolizing microsphere via internal carotid artery, and were given Sailuotong treatment (16.5 and 33.0 mg x kg(-1)) for 60 days. The pathological changes in brain ultrastructure were observed by transmission electron microscope. The levels of Glu and GABA in brain tissue were measured with high performance liquid chromatography. The expression of NMDA receptors including NR1, NR2A and NR2B in neurons was evaluated by immunohistochemical staining. Compared with the sham rats, abnormal changes were observed in ultrastructures of neurons, neuroglia cells and synapses of model rat brains. Moreover, significant decrease of Glu and GABA, as well as the elevated expression of NR1, NR2A and NR2B were detected in brain tissues. Sailuotong (16.5 and 33.0 mg x kg(-1)) could improve ultrastructure of cerebral tissue, facilitate synthesis of Glu and GABA, and down-regulate expression of NR1, NR2A and NR2B in neurons. The results demonstrated that Sailuotong could exert neuroprotective effects to some extent in the recovery phase of multiple cerebral infarction by promoting expression of NMDA receptors and synthesis of Glu and GABA.

[Numerical simulation on evolution and control of spiral wave in heart].

In this paper, the numerical simulation for evolution and control of spiral waves in 2D cardiac excitable media is performed; it can be represented as modified FitzHugh-Nagumo (FHN) model by selecting suitable parameter values. When the plane wave being cut, the system can evolve into a spiral wave. The excitability of media can produce effect on the stability of spiral wave. When the excitability is greater than the critical value, the spiral wave core and period tend towards infinity and disappear. The drifting ways of spiral wave tip are different (meandering) in various driving frequencies when one spiral wave is driven by uniform periodic small current. When period T is below or above the resonance period of spiral wave, the spiral wave is in its pedaflower or pediflower orbit, and if the driving period precisely equals the resonance period, the spiral wave tip drifts along a straight line.

[The heartbeat modes in modified Ikeda phase resetting model].

In this paper are proposed four heartbeat models which correspond to two different positions of the ectopic pacemaker and two coupling styles of the sinus and ectopic pacemakers. The models computed are based on the modified Ikeda phase resetting model. Most of the heartbeat modes are periodic; they exhibit "Arnold's tongue" structure in parameter plane of perturbing frequency and strength. When the ectopic pacemaker is located in the ventricle, there are bistable dynamic modes. The abnormal hearbeat rhythms of bigeminy and trigeminy in clinical medicine have been observed when coupling strength is weaker in odd resetting or refractory time is longer in even resetting.

[Effective control of excitable waves in 2D cardiac excitable media].

We propose a method for effective control of patter on dissipative system by use of little perturbation analysis, and apply this nonuniform feed back method to control the polarization wave of heart represented by FHN equation. In the numerical experiment, we successfully alter the propagating direction of planar waves and drift the spiral waves to boundary without resonant repulsion. The effective control of the excited system will be used to study the mechanism of defibrillation and that is our interesting work.