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 ...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.展开更多
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...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.展开更多
BACKGROUND Blood pressure variability(BPV)has been shown to be related to mild cognitive impairment and Alzheimer's disease in a number of studies.However,the relationship between BPV and subtle cognitive decline(...BACKGROUND Blood pressure variability(BPV)has been shown to be related to mild cognitive impairment and Alzheimer's disease in a number of studies.However,the relationship between BPV and subtle cognitive decline(SCD)has received minimal attention in this field of research to date and has rarely been reported.AIM To examine whether SCD is independently associated with changes in BPV in older adults.METHODS Participants were selected based on having participated in cognitive function evaluation and ambulatory blood pressure measurement at the Shanghai Sixth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine between June 2020 and August 2022.The participants included 182 individuals with SCD as the experimental group and 237 with normal cognitive function as the control group.The basic data,laboratory examinations,scale tests,and ambulatory blood pressure test results of the two groups were analyzed retrospectively,and the relationship between SCD and BPV was subsequently evaluated.RESULTS Significant differences were observed between the two groups of participants(P<0.05)in terms of age,education level,prevalence rate of diabetes,fasting blood glucose level,24-h systolic blood pressure standard deviation and coefficient of variation,24-h diastolic blood pressure standard deviation and coefficient of variation.The scale monitoring results showed significant differences in the scores for memory,attention,and visual space between the experimental and control groups.Logistic regression analysis indicated that age,education level,blood sugar level,and BPV were factors influencing cognitive decline.Linear regression analysis showed that there was an independent correlation between blood pressure variation and SCD,even after adjusting for related factors.Each of the above differences was still significant.CONCLUSION This study suggests that increased BPV is associated with SCD.展开更多
Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavio...Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.展开更多
Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impai...Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.展开更多
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 infarct...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 Zhen 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.展开更多
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-1-phenyl-2-pyrazolin-5-one, eda...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-1-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.展开更多
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 ...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 CuCl_ 2 . 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.展开更多
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.Cardiomyo...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.展开更多
To investigate the effects of impaired glucose metabolism (IGM) on cardiovascular autonomic nervous systems in essential hypertensive (EH) patients by comparing heart rate variabil-ity (HRV) and blood pressure variabi...To investigate the effects of impaired glucose metabolism (IGM) on cardiovascular autonomic nervous systems in essential hypertensive (EH) patients by comparing heart rate variabil-ity (HRV) and blood pressure variability (BPV) in EH patients with or without type 2 diabetes melli-tus (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 com-ponent along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was rep-resented 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 complica-tions in the EH patients with IGM.展开更多
Objective To investigate the effect of phenylephrine(an α-adrenergic agonist) on alveolar fluid clearance(AFC) in ventilator-induced lung injury and the possible mechanism involved.Methods A total of 170 male Wistar ...Objective To investigate the effect of phenylephrine(an α-adrenergic agonist) on alveolar fluid clearance(AFC) in ventilator-induced lung injury and the possible mechanism involved.Methods A total of 170 male Wistar rats were randomly allocated into 17 groups(n=10) using random number tables.Short-term(40 minutes) mechanical ventilation with high tidal volume(HVT) was performed to induce lung injury,impair active Na + transport and lung liquid clearance in the rats.Unventilated rats served as controls.To demonstrate the effect of phenylephrine on AFC,phenylephrine at different concentrations(1×10-5,1×10-6,1×10-7,1×10-8,and 1×10-9 mol/L) was injected into the alveolar space of the HVT ventilated rats.To identify the influence of adrenergic antagonists,Na + channel,and microtubular system on the effect of phenylephrine,phenylephrine at 1×10-5 mol/L combined with prazosin(an α 1-adrenergic antagonist,1×10-4 mol/L),yohimbine(an α 2-adrenergic antagonist,1×10-4 mol/L),atenolol(a β 1 adrenergic antagonist,1×10-5 mol/L),ICI-118551(an β 2-adrenergic antagonist,1×10-5 mol/L),amiloride(a Na + channel blocker,5×10-4 mol/L),ouabain(a Na + /K +-ATPase blocker,5×10-4 mol/L),colchicine(a microtubular disrupting agent,0.25 mg/100 g body weight),or β-lumicolchicine(an isomer of colchicine,0.25 mg/100 g body weight) were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes.AFC and total lung water content were measured.Results Basal AFC in control rats was(17.47±2.56)%/hour,which decreased to(9.64± 1.32)%/hour in HVT ventilated rats(P=0.003).The perfusion of phenylephrine at 1×10-8,1×10-7,1×10-6,and 1×10-5 mol/L significantly increased the AFC in HVT ventilated rats(all P<0.05).This effect of phenylephrine on AFC was suppressed by prazosin,atenolol,and ICI-118551 in HVT ventilated rats by 53%,31%,and 37%,respectively(all P<0.05).The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain,respectively(both P<0.05).Colchicine significantly inhibited the effect of phenylephrine(P=0.031).Conclusion Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the absorption of pulmonary edema.展开更多
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 a...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.展开更多
OBJECTIVE:To assess the clinical efficacy and safety of atorvastatin in the treatment of Alz-heimer's disease.DATA SOURCES:Medline(1948/2011-04),Embase(1966/2011-04),Cochrane Library(Issue 3,2011),Chinese National...OBJECTIVE:To assess the clinical efficacy and safety of atorvastatin in the treatment of Alz-heimer'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 lan-guage.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 Alzheimer disease,dementia,cognition,affection,memory dysfunction,hydroxymethylglutaryl-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%CI:-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) com-pared with the placebo group.CONCLUSION:There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate Alzheimer'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.展开更多
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 ...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 μg/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-α(TNF-α), interleukin 17(IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeleddextran (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 m RNA 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-q PCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ.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.展开更多
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 dysp...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.展开更多
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 re...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.展开更多
Speckle tracking echocardiography(STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myoca...Speckle tracking echocardiography(STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge(G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group(n=10), mild trans-aortic banding(TAB) group(n=14) and severe TAB group(n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening(FS), left ventricular(LV) mass, and left ventricular end diastolic diameter(LVEDD)(P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures(P>0.05 for both). STE analysis revealed that longitudinal strain(LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups(P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group(P<0.05). Radial strain(RS) and circumferential strain(CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group(P<0.05 for both) from the postoperative week 1(P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6(P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.展开更多
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 contro...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.展开更多
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2020A1515010123 and No.2021A1515010695Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province,No.2019A030317011.
文摘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.
基金supported by the National Natural Science Foundation of China (U2004134)Zhengzhou University (140/32310295) to NWH+2 种基金by Science Foundation Ireland(19/FFP/6437 and 14/IA/2571) to MJRa scholarship granted by the China Scholarship Council (CSC20200704504 7) to YY
文摘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.
基金Shanghai Municipal Commission of Science and Technology Program,No.19411960900.
文摘BACKGROUND Blood pressure variability(BPV)has been shown to be related to mild cognitive impairment and Alzheimer's disease in a number of studies.However,the relationship between BPV and subtle cognitive decline(SCD)has received minimal attention in this field of research to date and has rarely been reported.AIM To examine whether SCD is independently associated with changes in BPV in older adults.METHODS Participants were selected based on having participated in cognitive function evaluation and ambulatory blood pressure measurement at the Shanghai Sixth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine between June 2020 and August 2022.The participants included 182 individuals with SCD as the experimental group and 237 with normal cognitive function as the control group.The basic data,laboratory examinations,scale tests,and ambulatory blood pressure test results of the two groups were analyzed retrospectively,and the relationship between SCD and BPV was subsequently evaluated.RESULTS Significant differences were observed between the two groups of participants(P<0.05)in terms of age,education level,prevalence rate of diabetes,fasting blood glucose level,24-h systolic blood pressure standard deviation and coefficient of variation,24-h diastolic blood pressure standard deviation and coefficient of variation.The scale monitoring results showed significant differences in the scores for memory,attention,and visual space between the experimental and control groups.Logistic regression analysis indicated that age,education level,blood sugar level,and BPV were factors influencing cognitive decline.Linear regression analysis showed that there was an independent correlation between blood pressure variation and SCD,even after adjusting for related factors.Each of the above differences was still significant.CONCLUSION This study suggests that increased BPV is associated with SCD.
基金supported by the National Natural Science Foundation of China,Nos.81801236(to ZX),81974189(to HT)a grant from Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.ynlc201719(to QZ).
文摘Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.
基金the National Natural Science Foundation of China(82171198,U20A20354)the Sci-Tech Innovation 2030 Agenda of China(2022ZD0211603).
文摘Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.
文摘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 Zhen 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.
基金the Talent Introduction Project of Affili-ated Hospital of Jiangsu University,No.jdfyRC 2008003
文摘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-1-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.
基金grants obtained from the National Natural Science Foundation of China （No.： 81170177, 81030002） and science and Technology De- partment of Gansu Province Project （145RJZ104）.
文摘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 CuCl_ 2 . 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.
基金supported by the National NaturalScience Foundation of China(NSFC 81570328,Wang Junhong)the"Sixth-Peak Talent"of Jiangsu Province(2011WSN-029 to Prof.Guo Yan and2013WSN-036 to Dr.Wang Junhong)support by the Health Department of Jiangsu Province(z201301)
文摘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.
文摘To investigate the effects of impaired glucose metabolism (IGM) on cardiovascular autonomic nervous systems in essential hypertensive (EH) patients by comparing heart rate variabil-ity (HRV) and blood pressure variability (BPV) in EH patients with or without type 2 diabetes melli-tus (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 com-ponent along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was rep-resented 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 complica-tions in the EH patients with IGM.
基金Supported by the Natural Science Foundation of Liaoning Province (201202245)
文摘Objective To investigate the effect of phenylephrine(an α-adrenergic agonist) on alveolar fluid clearance(AFC) in ventilator-induced lung injury and the possible mechanism involved.Methods A total of 170 male Wistar rats were randomly allocated into 17 groups(n=10) using random number tables.Short-term(40 minutes) mechanical ventilation with high tidal volume(HVT) was performed to induce lung injury,impair active Na + transport and lung liquid clearance in the rats.Unventilated rats served as controls.To demonstrate the effect of phenylephrine on AFC,phenylephrine at different concentrations(1×10-5,1×10-6,1×10-7,1×10-8,and 1×10-9 mol/L) was injected into the alveolar space of the HVT ventilated rats.To identify the influence of adrenergic antagonists,Na + channel,and microtubular system on the effect of phenylephrine,phenylephrine at 1×10-5 mol/L combined with prazosin(an α 1-adrenergic antagonist,1×10-4 mol/L),yohimbine(an α 2-adrenergic antagonist,1×10-4 mol/L),atenolol(a β 1 adrenergic antagonist,1×10-5 mol/L),ICI-118551(an β 2-adrenergic antagonist,1×10-5 mol/L),amiloride(a Na + channel blocker,5×10-4 mol/L),ouabain(a Na + /K +-ATPase blocker,5×10-4 mol/L),colchicine(a microtubular disrupting agent,0.25 mg/100 g body weight),or β-lumicolchicine(an isomer of colchicine,0.25 mg/100 g body weight) were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes.AFC and total lung water content were measured.Results Basal AFC in control rats was(17.47±2.56)%/hour,which decreased to(9.64± 1.32)%/hour in HVT ventilated rats(P=0.003).The perfusion of phenylephrine at 1×10-8,1×10-7,1×10-6,and 1×10-5 mol/L significantly increased the AFC in HVT ventilated rats(all P<0.05).This effect of phenylephrine on AFC was suppressed by prazosin,atenolol,and ICI-118551 in HVT ventilated rats by 53%,31%,and 37%,respectively(all P<0.05).The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain,respectively(both P<0.05).Colchicine significantly inhibited the effect of phenylephrine(P=0.031).Conclusion Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the absorption of pulmonary edema.
基金This project was supported by grants from the National Natural Science Foundation of China ( No.30271242,30371396).
文摘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.
文摘OBJECTIVE:To assess the clinical efficacy and safety of atorvastatin in the treatment of Alz-heimer'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 lan-guage.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 Alzheimer disease,dementia,cognition,affection,memory dysfunction,hydroxymethylglutaryl-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%CI:-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) com-pared with the placebo group.CONCLUSION:There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate Alzheimer'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.
基金the Scientific Research Foundation of HealthDepartment of Hebei Province,No.20160483
文摘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 μg/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-α(TNF-α), interleukin 17(IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeleddextran (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 m RNA 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-q PCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ.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.
文摘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.
基金supported by the National Natural Science Foundation of China,No.81171147“Key Medical Talents of Qiangwei Project” Research Foundation of Health Department of Jiangsu Province of China,No.ZDRCA2016010+1 种基金“Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province of China,No.RC201156Jiangsu Provincial Key Discipline of Medicine of China,No.XK201117(all to LXL)
文摘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.
基金supported by grants from the National Natural Science Foundation of China(No.81400255)the Hubei Science&Technology Pillar Program of China(No.2012DCA12007)the Hubei Public Welfare Science Research Program of China(No.2013BCB023)
文摘Speckle tracking echocardiography(STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge(G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group(n=10), mild trans-aortic banding(TAB) group(n=14) and severe TAB group(n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening(FS), left ventricular(LV) mass, and left ventricular end diastolic diameter(LVEDD)(P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures(P>0.05 for both). STE analysis revealed that longitudinal strain(LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups(P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group(P<0.05). Radial strain(RS) and circumferential strain(CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group(P<0.05 for both) from the postoperative week 1(P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6(P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.
文摘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.
