AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis:A case report and review of literature

BACKGROUND Venous thromboembolism significantly contributes to patient deterioration and mortality.Management of its etiology and anticoagulation treatment is intricate,necessitating a comprehensive consideration of various factors,including the bleeding risk,dosage,specific anticoagulant medications,and duration of therapy.Herein,a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience.CASE SUMMARY An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d.Considering her medical history and relevant post-admission investigations,it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors,including multiple primary malignant tumors,iliac venous compression syndrome,previous novel coronavirus infection,and inadequate treatment for prior thrombotic events.However,the selection of appropriate anticoagulant medications,determination of optimal drug dosages,and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia,decreased quantitative fibrinogen levels,and renal insufficiency.CONCLUSION Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis.Individualized anticoagulation therapy is required for complex thrombosis.

Microglia in brain aging:An overview of recent basic science and clinical research developments

Aging is characterized by progressive degeneration of tissues and organs,and it is positively associated with an increased mortality rate.The brain,as one of the most significantly affected organs,experiences age-related changes,including abnormal neuronal activity,dysfunctional calcium homeostasis,dysregulated mitochondrial function,and increased levels of reactive oxygen species.These changes collectively contribute to cognitive deterioration.Aging is also a key risk factor for neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.For many years,neurodegenerative disease investigations have primarily focused on neurons,with less attention given to microglial cells.However,recently,microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis.Here,we provide an overview of brain aging from the perspective of the microglia.In doing so,we present the current knowledge on the correlation between brain aging and the microglia,summarize recent progress of investigations about the microglia in normal aging,Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis,and then discuss the correlation between the senescent microglia and the brain,which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.

Exogenous insulin autoimmune syndrome:A case report and review of literature

BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.

Optimism,Social Support,and Caregiving Burden among the Long-Term Caregivers:The Mediating Effect of Psychological Resilience

Background:As the elderly population grows,the demand for long-term care services is increasing.Despite significant investments in care quality and workforce training,long-term care workers often face challenges such as work fatigue,heavy workloads,and inadequate support.These issues can impact job satisfaction,mental health,and care quality,leading to staff turnover.This study examines how optimism,social support,and psychological resilience relate to caregiving burden,aiming to understand their effects on caregivers’well-being and performance to enhance the quality of long-term care services.Methods:The participants were 542 long-term care workers.Descriptive statistics,t-tests,one-way ANOVA,and hierarchical regression were used for data analysis.Results:(1)Optimism and social support were significantly and positively correlated with psychological resilience and significantly and negatively associated with caregiving burden.(2)Regarding differences in optimism,social support,psychological resilience,and caregiving burden among long-term care workers,females scored significantly higher than males in“social support;”married workers scored significantly higher than unmarried workers in“optimism,”“social support,”and“psychological resilience”;workers aged 45–65 scored significantly higher than those aged 25–45 in“optimism”;workers aged 25–45 scored significantly higher than those aged 45–65 in“caregiving burden”;social workers scored significantly higher than nursing staff in“optimism.”(3)Psychological resilience partially mediated the relationship between social support and caregiving burden concerning explanatory and predictive power.Conclusions:These findings suggest that optimism,social support,and psychological resilience are essential factors in reducing the caregiving burden among long-term care workers.The study highlights the importance of promoting psychological resilience and providing social support to alleviate the burden of caregiving.

Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis:Implications for bone health

BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.

Use of acupuncture to treat cerebral infarction in the last 10 years A Scopus-based literature analysis

OBJECTIVE： To identify global research trends in the use of acupuncture to treat cerebral infarction. DATA RETRIEVAL： We performed a bibliometric analysis of studies on the use of acupuncture to treat cerebral infarction published during 2002-2011, retrieved from Scopus, using the key words of acupuncture and cerebral infarction or ischemic stroke. SELECTION CRITERIA： Inclusion criteria： peer-reviewed articles on the use of acupuncture to treat cerebral infarction indexed in Scopus and published between 2002 and 2011; types of publications were original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria： articles that required manual searching or telephone access; documents that were not published in the public domain; and corrected papers. MAIN OUTCOME MEASURES： （a） Annual publication output; （b） language of publication; （c） type of publication; （d） key words of publication; （e） publication by research field; （f） publication by journal （g） publication by country and institution; （h） publication by author; （i） most-cited papers between 2002 and 2006; and （j） most-cited papers between 2007 and 2011. RESULTS： A total of 160 publications on the use of acupuncture to treat cerebral infarction from 2002-2011 were retrieved from Scopus. The number of publications increased gradually over the 10-year study period; most were written in Chinese or English. Articles and reviews constituted the major types. The most frequent key word used was acupuncture. The most prolific journals in this area were Zhongguo 7hen Jiu and the Chinese Journal of Clinical Rehabilitation. Of the 160 publications retrieved, half came from Chinese authors and institutions. Tianjin University of Traditional Chinese Medicine was the most prolific research institute. Two papers were cited 30 times; they were published in 2002 and 2009, respectively. CONCLUSION： In the field of neuroscience, there is little literature on acupuncture for cerebral infarction. The most-cited papers were cited 30 times in the past 3 years. We believe that, with advances in the study of mechanisms in neurobiology, research on acupuncture will also advance and will become the concern of more scholars.

Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome： the role of hyperglycemia and obesity

Background Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease （CAD）, CAD patients with metabolic syndrome （MS） still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention （PCI）. Methods Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography （CAG） were enrolled in our study. MS was defined by modified Adult Treatment Panel Ⅲ criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry （LTA） and thrombelastography （TEG）. Clopidogrel resistance was defined as more than 50% adenosine diphosphate （ADP） induced platelet aggregation as measured by TEG. Re- sults Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG （55% ＋ 31% vs. 68% ± 32%; P 〈 0.001） and LTA （29% ± 23% vs. 42% ± 29%; P 〈 0.001）. In the multivariate analysis, elderly [OR （95% CI）： 1.483 （1.047±.248）; P = 0.002], obesity [OR （95% CI）： 3.608 （1.241-10.488）; P = 0.018], high fasting plasma glucose level [OR （95% CI）： 2.717 （1.176±.277）; P = 0.019] and hyperuricemia [OR （95% CI）： 2.583 （1.095-6.094）; P = 0.030] were all statistically risk factors for clopido- grel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without dia- betes and obesity [75% （61/81） vs. 43% （67/156）; P 〈 0.001]. Conclusions CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopido- grel resistance.

Protective effects of MCI-186 on oxidative damage in a cell model of Alzheimer's disease

Oxidative stress has an important role in the development of Alzheimer＇s disease （AD）. Beta amyloid protein 25-35 （Aβ25-35） can generate oxygen free radicals, and MCI-186 （3-methyl-l-phenyl-2-pyrazolin-5-one, edaravone） can specifically eliminate hydroxyl radicals. The present study introduced Aβ25-35 into PC12 cells to establish a cell model of AD, and investigated the neuroprotective effects of MCI-186 on AD. Results showed that MCI-186 had a positive effect on the prevention and treatment of AD by inhibiting protein oxidative products, advanced glycation end products, lipid oxidative end products and DNA oxidative damage in PC12 cells induced by Aβ25-35.

Characterization of a Chinese KCNQ1 mutation （R259H） that shortens repolarization and causes short QT syndrome 2

Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members （63 patients）. We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that en- code ion channels which contribute to the repolarization of the ventricular action potential, including KCNQI, KCNH2, KCNE1, KCNE2, KCNJ2, CACNAlc, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ 1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type （WT） after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation （P 〉 0.05）, whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current （Irs） in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function muta- tion of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people.

Pitavastatin attenuates AGEs-induced mitophagy via inhibition of ROS generation in the mitochondria of cardiomyocytes

This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs（100 μg/mL）,receptor for advanced glycation end products（RAGE）,antibody（1 μg/mL） and pitavastatin（600 ng/mL）.The levels of p62 and beclinl were determined by Western blotting.Mitochondrial membrane potential（△Ψm） and the generation of reactive oxygen species（ROS） were measured through the JC-1 and DCFH-DA.In the AGEs group,the expression of beclinl was remarkably increased compared to the control group,while the expression of p62 was significantly decreased.AGEs also markedly decreased △Ψm and significantly increased ROS compared with the control group.After treatment with RAGE antibody or pitavastatin,the level of beclinl was markedly decreased compared with the AGEs group,but the level of p62 was remarkably increased.In the AGEs ＋ RAGE antibody group and AGEs＋ pitavastatin group,△Ψm was significantly increased and ROS was remarkably decreased compared with the AGEs group.In conclusion,AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.

Effects of Impaired Glucose Metabolism on Heart Rate Variability and Blood Pessure Variability in Essential Hpertensive Patients

To investigate the effects of impaired glucose metabolism （IGM） on cardiovascular autonomic nervous systems in essential hypertensive （EH） patients by comparing heart rate variability （HRV） and blood pressure variability （BPV） in EH patients with or without type 2 diabetes mellitus （T2DM）. Simultaneous 24-h recordings of ambulatory ECG and blood pressure monitoring were performed in 36 male old patients with simple EH and 33 male old patients with EH combined with T2DM. HRV analysis included time domain parameters such as SDNN, SDANN, SDNNi, rMSSD and pNN50, and total spectral power （TP） of HRV, which mainly consists of VLF, LF and HF component along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was represented as the mean blood pressure （mean systolic/mSBP, diastolic/mDBP and pulse pressure/mPP） during different periods （24 h/24 h, day time/d and night time/n）. Standard deviation （SD） as well as coefficient of variance （CV） of blood pressure during each above-mentioned period were obtained to reflect the long-term BPV. Our result showed that SDNN, SDNNi, SDANN, rMSSD, PNN50, TP and HF of HRV in cases of EH with T2DM were all significantly lower than those in simple EH subjects （P〈0.05）. No significant differences in VLF or LF was found between the two groups （P〉0.05）, while LF/HF ratio was significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.01）. Moreover, dmSBP, 24 h-mPP and dmPP were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while nmSBP, 24 h-mSBP, 24 h-mDBP, dmDBP, nmDBP or nmPP showed no significant difference between this two groups of patients （P〉0.05）. And dSBPSD, dSBPCV and 24 h-SBPSD were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while the other BPV indexes showed no significant difference between this two groups （P〉0.05）. It is concluded that the cardiovascular autonomic nervous systems in EH patients was further impaired by T2DM, displaying lowering of HRV and enlargement of BPV, which in turn induced abnormal structural and functional changes of cardiovascular systems. Therefore, improving cardiovascular autonomic nervous systems might reduce the occurrence of cardiovascular complications in the EH patients with IGM.

Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis

AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 mu g/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-a (TNF-alpha), interleukin 17 (IL-17) and interferon-. (IFN-gamma). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-alpha, IL-17 and IFN-gamma. CONCLUSION Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.

Mechanisms of Increased Expression of Toll-Like Receptor-4 in Human Monocyte/Macrophage-derived Foam Cells

Summary： The mechanisms of increased expression of toll-like receptor 4 （TLR-4） during the formation of foam cells were explored. Low density lipoprotein （LDL） was prepared by density gradient ultracentrifugation and oxidized by incubation with CuClz. The human monocytic leukemia cell line （THP-1） was cultured in RPMI1640. The differentiation of THP-1 cells into macrophages （MPs） was induced by using myristate acetate （PMA） for 48 h. The macrophages were then incubated with oxidized LDL （ox-LDL） to generate foam cells （FCs）. The mRNA and protein expression levels of human TLR-4 were detected by immunocytochemistry, Western blotting and reverse transcription polymerase chain reaction （RT-PCR）. The results showed that the TLR-4 mRNA and the protein expression levels were significantly increased during the differentiation of monocytes into macrophages （P〈0. 05） as well as during the formation of lipid-laden foam cells （P〈0.05）. It was concluded that the upregulation of human TLR-4 gene expression during the differentiation of monocytes into macrophages and the differentiation of macrophages into foam cells could increase TLR-4 protein synthesis dramatically, which may enhance the ability of foam cells inflammation reaction in atherosclerosis.

Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries:a meta-analysis

Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically relevant,standardized rat model of contusion SCI were identified by searching the PubMed,Embase and Cochrane databases,and the extracted data were analyzed by Stata 14.0.Data selection:Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso,Beattie,and Bresnahan lo-comotor rating scale.Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.Outcome measures:The restoration of motor function was assessed by the Basso,Beattie,and Bresnahan locomotor rating scale.Results:We identified 1756 non-duplicated papers by searching the aforementioned electronic databases,and 30 full-text articles met the inclusion criteria.A total of 37 studies reported in the 30 articles were included in the meta-analysis.The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs,to a moderate extent(pooled standardized mean difference(SMD)=0.73;95%confidence interval(CI):0.47–1.00;P<0.001).NSCs obtained from different donor species(rat:SMD=0.74;95%CI:0.36–1.13;human:SMD=0.78;95%CI:0.31–1.25),at different donor ages(fetal:SMD=0.67;95%CI:0.43–0.92;adult:SMD=0.86;95%CI:0.50–1.22)and from different origins(brain-derived:SMD=0.59;95%CI:0.27–0.91;spinal cord-derived:SMD=0.51;95%CI:0.22–0.79)had similar efficacies on improved functional recovery;however,adult induced pluripotent stem cell-derived NSCs showed no significant efficacies.Furthermore,the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery(SMD=0.45;95%CI:0.21–0.70).However,shorter periods between the contusion induction and the NSC transplantation showed slightly higher efficacies(acute:SMD=1.22;95%CI:0.81–1.63;subacute:SMD=0.75;95%CI:0.42–1.09).For chronic injuries,NSC implantation did not significantly improve functional recovery(SMD=0.25;95%CI:–0.16 to 0.65).Conclusion:NSC transplantation alone appears to be a positive yet limited method for the treatment of contusion SCIs.

Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer’s disease?

Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.

Prokaryotic Expression and Biological Activity Analysis of Human Arresten Gene

To express recombinant arresten in Escherichia coli (E.Coli) and investigate its biological activity, prokaryotic expression vector of human arresten gene was constructed by gene engineering. Human arresten gene was amplified from recombinant plasmid pGEMArr by polymerase chain reaction (PCR), and inserted into prokaryotic expression vector pRSET containing T7 promoter. Restriction analysis and DNA sequencing verified that the arresten gene was correctly cloned into the expression vector. The recombinant plasmid pRSETAt was subsequently transformed into E.coli BL21 (DE3), and the target gene was expressed under induction of IPTG. SDS-PAGE analysis revealed that the recombinant protein with a molecular weight of 29 kD (1 kD=0.992 1 ku) amounted to 29 % of the total bacterial proteins. After purification and renaturation, the recombinant protein could significantly suppress the proliferation of human umbilical vein endothelial cells (HUVECs). These results suggested that the expression of a biologically active form of human arresten in the pRSET expression system laid a foundation for further study on the mechanistic insight into arresten action on angiogenesis and the development of powerful anti-cancer drugs.

Investigation of compensatory postures with videofluoromanometry in dysphagia patients

AIM: To investigate the effectiveness of head compensatory postures to ensure safe oropharyngeal transit. METHODS: A total of 321 dysphagia patients were enrolled and assessed with videofluoromanometry (VFM). The dysphagia patients were classified as follows: safe transit; penetration without aspiration; aspiration before, during or after swallowing; multiple aspirations and no transit. The patients with aspiration or no transit were tested with VFM to determine whether compensatory postures could correct their swallowing disorder. RESULTS: VFM revealed penetration without aspiration in 71 patients (22.1%); aspiration before swallowing in 17 patients (5.3%); aspiration during swallowing in 32 patients (10%); aspiration after swallowing in 21 patients (6.5%); multiple aspirations in six patients (1.9%); no transit in five patients (1.6%); and safe transit in 169 patients (52.6%). Compensatory postures guaranteed a safe transit in 66/75 (88%) patients with aspiration or no transit. A chin-down posture achieved a safe swallow in 42/75 (56%) patients, a head-turned posture in 19/75 (25.3%) and a hyperextended head posture in 5/75 (6.7%). The compensatory postures were not effective in 9/75 (12%) cases. CONCLUSION: VFM allows the speech-language therapist to choose the most effective compensatory posture without a trial-and-error process and check the effectiveness of the posture.

Systematic review of atorvastatin for the treatment of Alzheimer's disease

OBJECTIVE： To assess the clinical efficacy and safety of atorvastatin in the treatment of Alzheimer＇s disease. DATA SOURCES： Medline （1948/2011-04）, Embase （1966/2011-04）, Cochrane Library （Issue 3, 2011）, Chinese National Knowledge Infrastructure （1989/2011-04）, and the Chinese Biomedical Literature Database （1979/2011-04） were searched for randomized clinical trials regardless of language. Abstracts of conference papers were manually searched. Furthermore, Current Controlled Trials （http：//controlled-trials.com）, Clinical Trials.gov （http：//clinicaltrials.gov）, and Chinese Clinical Trial Registry （http：//www.chictr.org） were also searched. Key words included AIzheimer disease, dementia, cognition, affection, memory dysfunction, hydroxymethylglutaryI-CoA reductase inhibitors, atorvastatin and statins. DATA SELECTION： Randomized controlled trials of grade A or B according to quality evaluation criteria of the Cochrane Collaboration were selected, in which atorvastatin and placebo were used to evaluate the effects of atorvastatin in the treatment of Alzheimer＇s disease. Study methodological quality was evaluated based on criteria described in Cochrane Reviewer＇s Handbook 5.0.1. Revman 5.1 software was used for data analysis. MAIN OUTCOME MEASURES： Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects. RESULTS： Two randomized controlled trials were included, one was scale A, and the other was scale B. All patients （n = 710, age range 50-90 years） were diagnosed as probable or possible mild to moderate Alzheimer＇s disease according to standard criteria and treated with atorvastatin 80 mg/d or placebo. There was no difference between the two groups in the final follow-up for Clinical Global Impression of Change scale （WMD = 0.13, 95%CI： 0.15 to 0.40）, the Alzheimer＇s Disease Assessment Scale-cognitive subscale （WMD = 1.05, 95%C1：-3.06 to 6.05）, Mini-Mental State Examination Scale （WMD = 0.77, 95%CI： 0.57 to 2.10）, and the Neuropsychiatric Instrument （WMD = 2.07, 95%CI： 1.59 to 5.73）. The rates of abnormal liver function, withdrawal from treatment, and withdrawal due to adverse effects were higher in the treatment group （OR = 7.86, 95%CI： 2.50 24.69; OR = 4.70, 95%CI： 2.61 8.44; and OR = 5.47, 95%CI： 3.01-9.94; respectively） compared with the placebo group. CONCLUSION： There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate AIzheimer＇s disease, because there was no benefit on general function, cognitive function or mental/behavior abnormality outcome measures. Efficacy and safety need to be confirmed by larger and higher quality randomized controlled trials, especially for moderate to severe Alzheimer＇s disease, because results of this systematic review may be limited by selection bias, implementation bias, as well as measurement bias.

Clinical Observation on Breviscapine in Treating Hypertension Patients Complicated with Micro-albuminuria of Renal Impairment

Objective: To evaluate the efficacy of Breviscapine on essential hypertension (EH) patients complicated with micro-albuminuria of renal impairment. Methods: Seventy-six EH patients were randomly assigned to the control group and the treated group, the former was given amlodipine, captopril/uropidil and the latter was given in addition Breviscapine intravenously dripped for 2 treatment courses. The indexes of serum creatinine (Cr), blood urea nitrogen (BUN), blood and urinary β 2-microglobulin (β 2-MG), and quantitative determination of 24 hrs urinary protein were evaluated before and after treatment. Results: In the control group, compared with before treatment, the quantitative determination of 24 hrs urinary protein got reduced significantly ( P <0.05), while in the treated group, both urinary β 2-MG and quantitative determination of 24 hrs urinary protein got lowered significantly ( P <0.05 and P <0.01). But after treatment, compared with the control group, urinary β 2-MG and quantitative determination of 24 hrs urinary protein in the treated group were obviously reduced ( P <0.05). Conclusion: Besides lowering blood pressure effectively, Breviscapine could improve the renal function significantly and reduce the urinary micro-albuminuria, hence showing promising effect on renal protection.