Effect of transcranial direct current stimulation combined with transcutaneous auricular vagus nerve stimulation on poststroke cognitive impairment: a study protocol for a randomised controlled trial.

INTRODUCTION: Poststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke. Transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) are non-invasive, safe treatments with great potential to improve cognitive function in poststroke patients. However, further improvements are needed in the effectiveness of a single non-invasive brain stimulation technique for cognitive rehabilitation. This study protocol aims to investigate the effect and neural mechanism of the combination of tDCS and taVNS on cognitive function in patients who had a stroke. METHODS AND ANALYSIS: In this single-centre, prospective, parallel, randomised controlled trial, a total of 66 patients with poststroke cognitive impairment will be recruited and randomly assigned (1:1:1) to the tDCS group, the taVNS group and the combination of tDCS and taVNS group. Each group will receive 30 min of treatment daily, five times weekly for 3 weeks. Primary clinical outcome is the Montreal Cognitive Assessment. Secondary clinical outcomes include the Mini-Mental State Examination, Stroop Colour Word Test, Trail Marking Test, Symbol Digit Modalities Test and Modified Barthel Index. All clinical outcomes, functional MRI and diffusion tensor imaging will be measured at preintervention and postintervention. ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of the First Affiliated Hospital of Yangtze University (approval no: KY202390). The results will be submitted for publication in peer-reviewed journals or at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300076632.

The role of high mobility group box 1 in neuroinflammatory related diseases.

High mobility group box 1 (HMGB1) is a ubiquitous and highly conserved non-histone DNA-binding protein with different biological functions according to its subcellular localization. It is widely believed that HMGB1, which is released into the extracellular space, plays a key role in the inflammatory response. In recent years, numerous studies have shown that the development of various neurological diseases such as epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), cerebrovascular disease and traumatic brain injury (TBI) are inextricably linked to inflammation. We will review the mechanisms of HMGB1 and its receptors in nervous system inflammation to provide a basis for further development of new HMGB1-based therapies.

The Progress of Functional Magnetic Resonance Imaging in Patients with Poststroke Aphasia.

Aphasia after stroke is one of the common complications of cerebral infarction. Early diagnosis and treatment of aphasia after stroke is of great significance for the recovery of language function. At present, there are different views on the pathogenesis of aphasia after stroke. Functional magnetic resonance imaging (fMRI) can reflect the brain function, brain tissue metabolism, and the level of brain local blood flow. It has the advantages of noninvasive, high resolution and sensitivity, low price, and so on. It has been widely used in the study of sensory aphasia after stroke. This study focuses on the development of functional magnetic resonance imaging in patients with poststroke aphasia and summarizes the published studies on functional magnetic resonance imaging in patients with poststroke aphasia. Evidence acquisition: A literature search was conducted in PubMed, Hindawi, PLoS, IEEE, Wiley, ScienceDirect, Springer, EMBASE, and web of science, with the keywords of "stroke" and "Aphasia" and "functional magnetic resonance imaging", "RS fMRI", or "DTI", to review the research of functional magnetic resonance imaging in patients with aphasia after stroke. The results included clinical evaluation, diagnostic scale, and imaging analysis; the study design was a randomized controlled trial, case series and case report, and observational study. A total of 67 articles were identified in the first search and 43 after the second search. Based on the analysis of 43 selected articles, 19 articles were included, and 24 articles were excluded. The selected information is shown in Table 1. Eleven of them did not contain imaging-related data. Six articles are related review articles. Four studies were conducted on patients without poststroke aphasia. Three studies studied the effect of poststroke aphasia on patients' social participation.

Combining electroacupuncture and transcranial direct current stimulation as an adjuvant therapy enhances spontaneous conversation and naming in subacute vascular aphasia: A retrospective analysis.

OBJECTIVE: Emerging evidence shows the effectiveness of speech and language therapy (SLT); however, precise therapeutic parameters remain unclear. Evidence for the use of adjunctive transcranial direct current stimulation (tDCS) to treat post-stroke aphasia (PSA) is promising; however, the utility of combining tDCS and electroacupuncture (EA) has not yet been analyzed. This study assessed the therapeutic consequences of EA and tDCS coupled with SLT in subacute PSA patients who were also undergoing hyperbaric oxygen therapy (HBOT). METHODS: A retrospective analysis was conducted on subacute (< 6 months) PSA patients who were divided into three groups: patients who received EA plus tDCS (acupuncture group), patients who underwent tDCS (tDCS group), and patients who experienced conventional therapy (HBOT + SLT). All subjects underwent 21 days of treatment and also received conventional treatment. The aphasia battery of Chinese (ABC) was used to score pre- and post-intervention status. RESULTS: The analysis comprised 238 patients. Cerebral infarction was the most frequent stroke type (137 [57.6%]), while motor (66 [27.7%]) and global aphasia (60 [25.2%]) were the most common types of aphasia. After 21 days of intervention, the ABC scores of all patients were improved. The acupuncture group had the highest ABC scores, but only repetition, naming, and spontaneous speech were statistically improved (P < 0.01). Post-hoc tests revealed significant improvement in word retrieval in the acupuncture and tDCS groups (P < 0.01, P = 0.037), while the acupuncture group had additional significant improvement in spontaneous conversation (P < 0.01). CONCLUSION: Combining acupuncture and tDCS as an adjuvant therapy for subacute PSA led to significant spontaneous speech and word retrieval improvements. Future prospective, multi-ethnic, multi-center trials are warranted.

The neurological insights of the emerging coronaviruses.

Emerging Viral diseases are incredibly infectious and proficient in inducing pandemics. Unlike the previous emerging coronaviruses (ECoVs) which neurological complexities were uncommon, with neurological features exhibition at 14-25 days post-onset, yet with critical outcomes exhibiting >50% mortality in central nervous (CNS) presenting pathologies. The COVID 19 neurological consequences occur more frequently even in mild cases, presenting with CNS involvement in up to 25%, musculoskeletal and peripheral manifestation (PNM). Through preceding ECoVs case reports, the PNM not linked to fatal outcomes, however, required, repeated neuro-imaging as notable CT and MRI changes appeared as late as 21 days while the likelihood of Cerebrospinal fluid to test positive for ECoV was 25%, only in the CNS presenting cases. Owing to 44-60% myalgia presentation, risk of the high inflammatory state, and coagulation cascade abnormalities reported in ECoVs, testing for C-reactive protein, serum creatine kinase, and D-dimer level is mandatory. Presently, there is no antiviral medication or vaccination for the ECoVs, early induction of antiviral drugs remains the backbone of management. Neurologically, the therapeutic dosages of anticoagulants are linked to the high incidence of thrombotic complexities, while methylprednisolone is associated with myopathy. Future studies expected to apply more neuro-imaging techniques for CNS exploration and further explore the pathogenesis of the COVID 19 myalgia, anosmia/ageusia reported in the majority of the initial cases.

A Novel Frequency Domain Impedance Sensor with a Perforated Cylinder Coaxial Design for In-Situ Measuring Soil Matric Potential.

Soil matric potential is an important parameter for agricultural and environmental research and applications. In this study, we developed a novel sensor to determine fast and in-situ the soil matric potential. The probe of the soil matric potential sensor comprises a perforated coaxial stainless steel cylinder filled with a porous material (gypsum). With a pre-determined gypsum water retention curve, the probe can determine the gypsum matric potential through measuring its water content. The matric potential of soil surrounding the probe is inferred by the reading of the sensor after the soil reaches a hydraulic equilibrium with the gypsum. The sensor was calibrated by determining the gypsum water retention curve using a pressure plate method and tested in three soil samples with different textures. The results showed that the novel sensor can determine the water retention curves of the three soil samples from saturated to dry when combined with a soil water content sensor. The novel sensor can respond fast to the changes of the soil matric potential due to its small volume. Future research could explore the application for agriculture field crop irrigation.

Calcium channels are involved in EphB/ephrinB reverse signaling­induced apoptosis in a rat chronic ocular hypertension model.

Erythropoietin-producing hepatocyte receptor B (EphB)/ephrinB reverse signaling has been revealed to be activated in chronic ocular hypertension (COH) by increasing the apoptosis of retinal ganglion cells (RGCs). However, the exact mechanism is not well understood. The present study investigated the involvement of Ca2+ channels in the apoptosis of RGCs induced by EphB/ephrinB reverse signaling in a rat CHO model, which was established by cauterizing 3 out of the 4 episcleral veins. The expression levels of four voltage­gated Ca2+ channel subunits (Cav3.1­3.3 and Cav1.2) were detected using immunofluorescence and western blot analysis. TUNEL staining was performed to assess RGC apoptosis following an injection with the T type Ca2+ channel blocker. Ca2+ channels, mainly the T type, were upregulated in COH rat retinas when compared with the sham group (P<0.01). Additionally, the Cav3.2 subunit of T type calcium channels was predominantly expressed in Müller cells and RGCs, such as ephrinB2. Furthermore, an intravitreal injection of the Ca2+ channel blocker Mibefradil (3 µM) reduced EphB2­fragment crystallizable region­induced RGC apoptosis in normal rats. Thus, the results suggest that Ca2+ channels in a COH model may be a pathway involved in ephrinB/EphB signaling­induced RGC apoptosis.

P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model.

Microglial activation and the release of pro­inflammatory cytokines occur during early glaucoma. However, the exact mechanism underlying the initiation of the microglial activation process remains unclear. Thus, the present study investigated the potential role of a purine receptor subtype, the P2X purinoceptor 7 (P2X7) receptor, during microglial activation in the retinal tissues of a rat chronic ocular hypertension (COH) model. This was achieved by cauterizing 3 of the 4 episcleral veins. Microglial activation and caspase­1 upregulation were observed in COH rat retinas by immunohistochemical and western blotting techniques. Intravitreal injection of 2',3'­O­(4­benzoylbenzoyl)­ATP (BzATP), a P2X7 receptor agonist, induced microglial activation in normal rat retinal tissues, which was alleviated by pretreatment with the P2X7 receptor antagonist, Brilliant Blue G (BBG). BBG further attenuated caspase­1 increment in COH rat retinal tissues. The data demonstrated that BBG reduced TUNEL­positive retinal ganglion cells in whole­mount retinal tissues with COH and normal retinal tissues following intravitreal injection with BzATP. One may conclude that the P2X7 receptor may be involved in microglial activation in the COH retina and could be considered a target for neuronal protection in glaucoma.

Overexpression of erythropoietin-producing hepatocyte receptor B4 and ephrin-B2 is associated with estrogen receptor expression in endometrial adenocarcinoma.

Endometrial adenocarcinoma (EC) is one of the most frequently diagnosed types of endometrial cancer and is typically a consequence of continuous estrogen receptor stimulation. Erythropoietin-producing hepatocyte receptor B4 (EphB4) and its ligand ephrin-B2 have been reported to be overexpressed in EC cells; however, the function in EC remains unclear. The present study aimed to elucidate the role of EphB4 and ephrin-B2 in EC. The protein expression pattern of EphB4 and ephrin-B2 was analyzed through immunohistochemistry and western blot analysis in endometrium with adenomyosis or simple endometrial hyperplasia, atypical endometrial hyperplasia, double-positive estrogen receptor (ER)/progesterone receptor (PR) EC and double-negative ER/PR EC. The expression of EphB4 and ephrin-B2 was demonstrated to be increased in atypical EH and ER/PR-positive EC, but not ER/PR-negative EC. Furthermore, EphB4 and ephrin-B2 expression was positively associated with ER expression in EC tissue. The results of the present study suggest that the overexpression of EphB4 and ephrin-B2 in the endometrium serves a role in the pathogenesis of EC, in addition to being associated with ER expression.

Multiple Kinases Involved in the Nicotinic Modulation of Gamma Oscillations in the Rat Hippocampal CA3 Area.

Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 µM nicotine, whereas none of them affected baseline γ oscillation strength. Inhibition of the serine/threonine kinase Akt increased baseline γ oscillations and partially blocked its nicotinic enhancement. We propose that the PKA-NMDAR-PI3K-ERK pathway modifies cellular properties required for the nicotinic enhancement of γ oscillations, dependent on a PKC-ERK mediated pathway. These signaling pathways provide clues for restoring γ oscillations in pathological conditions affecting cognition. The suppression of γ oscillations at 100 µM nicotine was only dependent on PKA-NMDAR activation and may be due to very high intracellular calcium levels.

Association between vascular endothelial growth factor polymorphism and recurrent pregnancy loss: A systematic review and meta-analysis.

PURPOSE: Some studies have reported that vascular endothelial growth factor (VEGF) genetic polymorphisms are associated with recurrent pregnancy loss (RPL), but the results are controversial. This study is aimed to quantify the strength of this association. METHODS: A systematic review of the published literature from Medline, Springer, and China National Knowledge Infra structure (CNKI) databases was conducted and investigations of VEGF genetic polymorphisms in RPL were selected. We estimated the pooled odds ratio (OR) to assess this possible association. RESULTS: Fifteen case-control studies comprising 2702 cases and 2667 controls and including five genetic polymorphisms (rs3025039, rs833061, rs15703060, rs2010963 and rs699947) were eligible for this meta-analysis. The overall analysis suggested that only two genetic polymorphisms (rs1570360, rs3025039) were associated with increased risk of RPL. A significant increased risk between VEGF rs1570360 polymorphism and RPL was only found under the dominant model in Caucasians (OR=1.70, 95% CI 1.02-2.82, P=0.04). Whereas, we found that VEGF rs3025039 polymorphism was significantly associated with RPL both under the dominant and recessive model in East Asians, and their summary odd ratios and 95% CIs were 1.26, 1.04-1.53, P=0.02 and 2.94, 1.80-4.83, P=0, respectively. CONCLUSIONS: This meta-analysis showed that only rs1570360 (especially in Caucasians) and rs3025039 (especially in East Asians) may be risk factors for RPL.

Association between rs1801133 polymorphism and risk of adult ischemic stroke: Meta-analysis based on case-control studies.

BACKGROUND: This study is aimed to quantify the strength of the association between rs1801133 polymorphism and ischemic stroke risk. METHODS: We have searched Medline, Springer, and Embase for studies investigating the association between rs1801133 polymorphism and ischemic stroke risk. We estimated the pooled odds ratio with its 95% confidence intervals to assess this possible association. RESULTS: Forty case-control studies comprising 8809 cases and 9130 controls are eligible for this meta-analysis on the basis of relation of rs1801133 polymorphism to ischemic stroke risk. Hardy-Weinberg equilibrium was used to perform in controls for excluding articles. The overall analysis suggested that rs1801133 polymorphism was associated with increased risk of ischemic stroke (ORT versus C=1.16, 95% CI 1.10-1.22; ORTT versus TC+CC=1.32, 95% CI 1.18-1.47; ORTT+TC versus CC=1.11, 95% CI 1.04-1.18). Subgroup analysis showed that T allele was a significant strength between T allele and stroke risk in Asian, Caucasian, male and young-middle populations (OR=1.19, 1.11, 1.30, 1.16, respectively). Compared with TC+CC, TT genotype was found to be a risk factor for developing ischemic stroke in Asian, Caucasian and male (OR=1.41, 1.20, 1.77, respectively). Additionally, TT+TC retained a significant increase for ischemic stroke only in Asian comparable to CC genotype (OR=1.14). CONCLUSIONS: The rs1801133 polymorphism could be capable of increasing ischemic stroke susceptibility in Asian, male and young-middle populations.

PTPN22 R620W Polymorphism is Associated with Myasthenia Gravis Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between PTPN22 R620W polymorphism and risk of myasthenia gravis (MG) remains controversial. Therefore, we did this meta-analysis to investigate this association. MATERIAL AND METHODS: We did a comprehensive search in PubMed, Medline, Embase, CNKI (China National Knowledge Infrastructure), and Wanfang electronic databases to retrieve relevant articles. The overall effect was measured by odds ratios (ORs) with its 95% confidence intervals (CIs). Statistical analyses were conducted with STATA software. RESULTS: Overall, a total of 7 case-control studies with 2802 cases and 3730 controls were finally included in this review. PTPN22 R620W polymorphism was significantly associated with an increased risk of MG (OR=1.57; 95% CI, 1.34-1.82; I(2)=31%). In the subgroup analysis, thymoma patients were significantly associated with risk of MG (OR=1.59; 95% CI, 1.28-1.98; I(2)=0%). However, non-thymoma patients with this polymorphism did not have increased MG risk (OR=1.36; 95% CI, 0.86-2.15; I(2)=77%). In addition, PTPN22 R620W polymorphism showed increased early-onset myasthenia gravis (EOMG) risk (OR=2.38; 95% CI, 1.52-3.71; I(2)=0%). CONCLUSIONS: This meta-analysis shows a significant association between PTPN22 R620W polymorphism and MG risk.

GluA2 trafficking is involved in apoptosis of retinal ganglion cells induced by activation of EphB/EphrinB reverse signaling in a rat chronic ocular hypertension model.

EphB1, expressed in Müller cells, and ephrinB2, expressed in both Müller cells and retinal ganglion cells (RGCs), constitute an EphB/ephrinB reverse signaling in RGCs. Whether and how this reverse signaling is involved in RGC apoptosis in a rat chronic ocular hypertension (COH) model was investigated. In the COH model, both EphB1 and ephrinB2 were significantly increased and the reverse signaling was activated, which was accompanied by increased protein levels of phosphorylated (p) src, GluA2, and p-GluA2. Intravitreal injection of EphB2-Fc, an activator of ephrinB2, induced an increase in TUNEL-positive signals in normal retinae. A coimmunoprecipitation assay demonstrated direct interactions among ephrinB2, p-src, and GluA2. Moreover, in COH rats the expression of GluA2 proteins on the surface of retinal cells was decreased. Such GluA2 endocytosis could be prevented by preoperational intravitreal injection of 4-amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo [3,4-d] pyrimidine (PP2), an inhibitor of src family tyrosine kinases, and possibly involved the protein interacting with C kinase 1 and phosphorylation of GluA2. In normal rats, intravitreal injection of EphB2-Fc caused changes in these protein levels similar to those observed in COH rats, which all could be avoided by preinjection of PP2. Patch-clamp experiments further showed that the current-voltage relationship of AMPA receptor-mediated EPSCs of RGCs exhibited stronger inward rectification in EphB2-Fc-injected rats. Furthermore, preinjection of PP2 or N-[3-[[4-[(3-aminopropyl)amino]butyl]amino]propyl]-1-naphthaleneacetamide trihydrochloride) (Naspm), a Ca(2+)-permeable GluA2-lacking AMPA receptor inhibitor, remarkably inhibited RGC apoptosis in either EphB2-Fc-injected or COH rats. Together, elevated GluA2 trafficking induced by activated EphB2/ephrinB2 reverse signaling likely contributes to RGC apoptosis in COH rats.

Rapid and quantitative detection of C-reactive protein using quantum dots and immunochromatographic test strips.

BACKGROUND: Rapid immunochromatographic tests can detect disease markers in 10-15 minutes, which facilitates clinical diagnosis and treatment programs. However, most immunochromatographic tests employ gold nanoparticles as reporters, and these have only moderate sensitivity and act as qualitative methods for analyzing high biomarker concentrations. METHODS: In this study, we introduce quantum dots (QDs) as fluorescent probes and immunochromatographic strips to develop quantitative fluorescence point-of-care tests (QF-POCT) to analyze C-reactive protein (CRP) levels. Goat anti-rabbit IgG and rabbit IgG were used as control antibodies, and mouse monoclonal CRP antibody pairs were used for disease marker detection. One monoclonal CRP antibody was conjugated with QDs and served as a signal antibody, and the other monoclonal CRP antibody was dispensed onto the nitrocellulose membrane and served as a capturing antibody. In the presence of CRP, the fluorescence intensity of the monoclonal antibody-CRP-monoclonal antibody sandwich complex captured on the nitrocellulose membrane was determined using the fluorescence strip reader. RESULTS: QF-POCT assays could quantitatively analyze the concentration of CRP in 15 minutes had a detection limit of 0.25 mg/L, and had a wide detection linearity range (0.5-300 mg/L). The intra-assay and interassay coefficients of variation were 8.95% and 9.86% at 0.5 mg/L, 6.47% and 8.66% at 10 mg/L, and 6.81% and 9.10% at 60 mg/L, respectively. In a comparison between clinical samples, the results of this QD-based assay of CRP levels were significantly correlated with those of an Immulite 2000 assay (R=0.993, P<0.001). CONCLUSION: Our results demonstrated that the QD-based immunochromatographic test is a rapid, sensitive, accurate, and quantitative method for the detection of disease biomarkers.

FCGR2A rs1801274 polymorphism is associated with risk of childhood-onset idiopathic (immune) thrombocytopenic purpura: evidence from a meta-analysis.

INTRODUCTION: Previous studies have evaluated the association between FCGR2A H131R (rs1801274) polymorphism and idiopathic (immune) thrombocytopenic purpura (ITP), but results remain inconsistent. This meta-analysis was conducted to clarify these controversies. METHODS: Literatures on PubMed/ Medline, Embase and CENTRAL databases up to September 2013 were searched by two investigators. The distributions of alleles and genotypes between cases and controls were compared by using odds ratios (ORs) and 95% confidence intervals (95% CIs). Fixed or Random-effects models were used when appropriate. RESULTS: 10 studies involving 553 patients and 1088 controls were available for this study, including 7 studies of Caucasian descendents, 2 studies of Asian descendents, and 1 study contained diverse ethnicity. In this studied overall population, we didn't found any significant association between the FCGR H131R polymorphism and the risk of ITP for all genetic models. But in the subgroup analysis, a significant association between FCGR H131R polymorphism and ITP susceptibility was observed in Caucasian population of childhood-onset group for H vs. R (OR = 1.246, 95% CI 1.021-1.522, p = 0.031), HH vs. HR + RR (OR = 1.562, 95% CI 1.145-2.129, p = 0.005), HH vs. HR (OR = 1.598, 95% CI 1.146-2.228, p = 0.006), HH vs. RR (OR = 1.484, 95% CI 1.005-2.191, p = 0.047). No significantly between-study heterogeneity was observed for all genotype models in Caucasian childhood-onset ITP subtype analysis. However, this association was not stable after sensitivity analysis. CONCLUSION: Our present meta-analysis indicated that FCGR H131R polymorphism might not be associated with risk of ITP in overall population. However, in Caucasian childhood-onset subgroup, there might be an association between FCGR2A H131R polymorphism and ITP risk, which is not robust and should be explained with caution.

Effect of arborvitae seed on cognitive function and α7nAChR protein expression of hippocampus in model rats with Alzheimer's disease.

The aim was to investigate the effect of the arborvitae seed on cognitive function and α7-nicotinic acetylcholine receptor (α7nAChR) protein expression of the hippocampus in model rats with Alzheimer's disease (AD). Thirty-six adult Wistar rats were randomly divided into the control, test, and drug groups. A dose of Aß1-40 was injected into the rats' hippocampus in the test and drug groups and the control rats were injected with the same amount of normal saline. After the model was successful, the rats in the control and test groups were gavaged with sodium carboxymethyl cellulose (500 mg/kg) and the rats in the drug group were gavaged with arborvitae seed powder (500 mg/kg) for 15 days. The Morris water maze test was used for cognitive function. The effect of arborvitae seed on α7nAChR protein immunoreactivity on the hippocampus neurons was studied by the immunohistochemistry method. Behavioral tests showed that the mean escape latencies and search time of the test group were obviously longer than the control and drug groups. The percentage of the search distance of the test group was shorter than that of the control and drug groups. The immunohistochemistry results are as follows: α7nAChR-positive cells and optical density in the hippocampus of the rats in the test group are less than that of the rats in the control and drug groups (all P < 0.01). Arborvitae seed can treat AD by increased expression of α7nAChR.

Establishment of a cerebral schistosomiasis experimental model in rabbits.

OBJECTIVE: The present study aimed to establish a cerebral schistosomiasis model in rabbits, to provide a valuable tool for morphological analysis, clinical manifestation observation, as well as investigations into immunological reactions and pathogenesis of focal inflammatory reaction in neuroschistosomiasis (NS). METHODS: Sixty New Zealand rabbits were randomly assigned into operation, sham-operation and normal groups. Rabbits in the operation group received direct injection of dead schistosome eggs into the brain, while their counterparts in the sham-operation group received saline injection. Rabbits in the normal group received no treatment. Base on the clinical manifestations, rabbits were sacrificed on days 3, 5, 7, 10, 20, and 30 post injection, and brain samples were sectioned and stained with hematoxylin-eosin. Sections were observed under the microscope. RESULTS: The rabbits in the operation group exhibited various neurological symptoms, including anorexy, partial and general seizures, and paralysis. The morphological analysis showed several schistosome eggs in the nervous tissue on day 3 post operation, with very mild inflammation. On days 7-10 post operation, several schistosome eggs were localized in proximity to red blood cells with many neutrophilic granulocytes and eosinophilic granulocytes around them. The schistosome eggs developed into the productive granuloma stage on days 14-20 post operation. On day 30, the schistosome eggs were found to be in the healing-by-fibrosis stage, and the granuloma area was replaced by fibrillary glia through astrocytosis. The sham-operation group and the normal group showed negative results. CONCLUSION: This method might be used to establish the cerebral schistosomiasis experimental model. Several factors need to be considered in establishing this model, such as the antigenic property of eggs, the time of scarification, and the clinical manifestations.

Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers.

BACKGROUND: Panax notoginseng (Burk) F.H. Chen is important medicinal plant of the Araliacease family. Triterpene saponins are the bioactive constituents in P. notoginseng. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the Panax species are largely unknown. RESULTS: Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for P. notoginseng root. These reads were processed and assembled by 454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST) similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS), which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old P. notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif. CONCLUSION: This study is the first to present a large-scale EST dataset for P. notoginseng root acquired by next-generation sequencing (NGS) technology. The candidate genes involved in triterpene saponin biosynthesis, including the putative CYP450s and UGTs, were obtained in this study. Additionally, the identification of SSRs provided plenty of genetic makers for molecular breeding and genetics applications in this species. These data will provide information on gene discovery, transcriptional regulation and marker-assisted selection for P. notoginseng. The dataset establishes an important foundation for the study with the purpose of ensuring adequate drug resources for this species.

[Strategies of the study on herb genome program].

Herb Genome Program (HerbGP) includes a series of projects on whole genome sequencing (WGS) and post-genomics research of medicinal plants with unique secondary metabolism pathways or/and those of great medical and pharmaceutical importance. In this paper, we systematically discussed the strategy of HerbGP, from species selection, whole-genome sequencing, assembly and bioinformatics analysis, to postgenomics research. HerbGP will push study on Chinese traditional medicines into the front field of life science, by selecting a series of plants with unique secondary metabolism pathways as models and introducing "omics" methods into the research of these medicinal plants. HerbGP will provide great opportunities for China to be the leader in the basic research field of traditional Chinese medicine. HerbGP shall also have significant impacts on the R&D of natural medicines and the development of medicinal farming by analysis of secondary metabolic pathways and selection of cultivars with good agricultural traits.