Aim Subcortical ischemic vascular demen-tia ( SIVD ) induced by chronic hypoperfusion due to small-artery disease is a common cause of vascular de-mentia ( VaD) , which is recognized as the second most prevalent type of dementia. The aim of this study was to determine whether carnosine played a protective role in cognitive impairment induced by permanent occlu-sion of the right unilateral common carotid arteries ( rUCCAO ) in SIVD. Methods Adult male mice ( C57BL/6 strain ) were subjected to rUCCAO, and treated with carnosine or saline. Locomotor test, open field test, hot plate test, freezing test and Morris water maze were performed after rUCCAO. Results There were no differences among rUCCAO group, carnosine group and sham group for total distance traveled in lo-comotor test. In the open field test, carnosine (200, 500 mg · kg-1 ) significantly revised the decrease of latency spent in the center induced by SIVD . There were no differences between rUCCAO and sham groups for the pain threshold. In freezing test, rUCCAO in-duced a significant reduction in content memory, which was completely reversed by treatment of carnosine. In Morris water maze training trials, rUCCAO-treated mice showed prolonged escape latency in acquisition phase, carnosine ( 200, 500 mg · kg-1 ) markedly shortened the escape latency. Conclusion These data suggest that carnosine has a neuroprotective effect on cognitive impairment induced by rUCCAO in mice.

Objective To compare the distribution and expression differences of glycogen synthase kinase-3?(GSK3?) among normal adult,aged and amyloid beta(A?)-induced neurodegenerative rat brains,so as to explore its functional role in neurodegeneration. Methods Aggregated A? was microinjected into normal adult rat hippocampus under a stereotaxic system. The rats over 12 months were defined as aged rats. The distribution and localization of GSK3? were examined using immunohistochemistry. Western blotting was performed to assess expression change in cortex and hippocampus quantitatively. Results The GSK3? positive cells were distributed extensively around the whole brain and almost with neuron-like morphology. In normal adult rats,the strong anti-GSK3? immunoreactivity located in the neocortex pyramidal layer,hippocampus pyramidal layer,dentate gyrus,thalamus,substantia nigra,etc. The amount of GSK3? positive cells was much more in the aged and A?-injected group than in normal ones. The immunoreactive signals usually extend to the distal area of neurite in the A?-injected ones. Western blot showed that the expression intensity of GSK3? was stronger in the aged and neurodegenerative rat brain than in the normal adult rat brain. Conclusion The expression of GSK3? increases apparently in the neurons of aged and A?-injected brain. It may play a role in the neurodegenerative process.

Objective To investigate the effect of lithium chloride(LiCl),an inhibitor of glycogen synthase kinase-3beta(GSK-3beta),on proliferation and differentiation of neural stem cells(NSCs).Methods The NSCs were isolated from cortex of rat fetus and expanded in culturing system.Their morphological changes and attachment process were observed under microscope.The cell cycle dynamics of NSCs was examined with flow cytometry.And the expression of GSK-3β and β-catenin was examined quantitatively with Western blot.Results The culturing NSCs treated with LiCl were usually floated and much dispersed in the media.Many of the neurospheres became small and the time of attachment after serum induction became longer.Using flow cytometry,it was detected that the proportion of G1 phase NSCs declined gradually accompanying the increased concentration of LiCl,while the percentage of S and G2/M phase cells showed an increasing trend.Western blotting results revealed β-catenin expression increased whereas Gsk-3βdecreased gradually under the treatment of LiCl and also showed a dose dependent manner.Conclusion These results suggest that LiCl may promote the proliferation of NSCs and prevent them from differentiating,which may partly involve the activation of wnt/β-catenin signaling pathway.

Objective to investigate the value of diffusion-weighted echo-planar MR imaging in the diagnosis of head and neck lesions.Methods Fifty-seven patients with 85 head and neck lesions were enrolled in the study,including 22 patients with 22 malignant tumors,13 patients with 13 benign tumors, 13 patients with 17 cystic and liquefactive lesions(including 8 patients with 12 cystic lesions,4 patients with 4 tumor necrosis,1 patients with 1 abcess)and 33 lymph nodes.The lesions were all confirmed by operation and clinical follow up.Echo-planar difffusion-weighted imaging (DWI)was performed with different b values (0,500,and 1,000s?mm~(-2)),and the apparent diffusion coefficients (ADCs)were measured.Results Malignant and benign tumors had different characteristics in DWI with different b values.With the increase of b value,the signal intensity of tumor/spinal cord ratio decreased quickly in DWI in benign tumors,while the signal intensity of tumor/spinal cord ratio remained similar in DWI in malignant tumors.The mean ADC value of'malignant tumors[(0.78?0.24)?10~(-3)mm~2? s~(-1)] was significantly lower than that of benign tumors [(1.48?+0.20)?10~(-3)mm~2?s~(-1)] (t = 8.9,P

Objective:To evaluate the clinical application of 64-slice spiral computer tomography pulmonary angiography (CTPA)in diagnosis of pulmonary embolism(PE).Methods:Sixty-two patients suspected of PE were examined by 64-slice spiral CTPA.The image findings combined with their clinical data were retrospectively analyzed.Results:Twenty-four of the 62 patients were confirmed to have PE by clinical data,laboratory examination and follow-up examination.64-slice spiral CTPA discovered 152 involved branches in the 24 PE patients,including 4 branches in left and right pulmonary trunk,52 in lobar pulmonary arteries,82 in segmental pulmonary arteries,and 14 in subsegmental arteries.Four types of PE were detected in our group,including eccentric filling defect in 58 branches,central filling defect in 49 branches,total occlusion of the pulmonary arteries in 21 branches,and mural embolism of host artery in 24 branches.The diagnosis accuracy of 64-slice spiral CTPA in the present group of patients was 100%,with no missed diagnosis and misdiagnosis.Besides,64-slice spiral CTPA could reflect the location,morphology,involvement and degrees of PE.Conclusion:64-slice spiral CTPA is a rapid,accurate and non-invasive diagnostic approach for PE.It is the first choice in clinical screening of PE and may serve as a gold standard for diagnosis of pulmonary embolism.

Background Clinical studies indicated that the pathogenesis of most corneal dystrophy is associated with the mutation of the transforming growth factor beta-induced (TGFBI) gene.However,the molecular mechanism of mutated TGFBI gene in corneal dystrophy is unclear. Objective The present study was to investigate the expression of the TGFBI gene in human corneal tissue and cells in vitro.MethodsHuman corneal epithelial cells and keratocytes were cultured and passaged,and donor corneal tissue was obtained for the section preparation.RT-PCR was used to detect the expression of TGFBI mRNA in human corneal tissue and cells.Immunofluorescence was used to test the expression of the TGFBI protein in the human corneal tissue,and immunohistochemistry was used to test the expression of the TGFBI protein in human corneal epithelial cells and corneal stromal cells.ResultsRT-PCR analysis showed that TGFBI mRNA could be detected as a 1274 bp band in human corneal tissue and corneal stromal cells,but no TGFBI mRNA was observed in corneal epithelial cells.Immunofluorescence assay revealed that corneal stromal cells were positive ly expressed for the TGFBI protein,but the corneal epithelial cells did not express the TGFBI protein.Immunohistochemistry indicated that the expression of TGFBI was detected the red fluoressence in the cytoplasm of corneal stromal cells;however,no positive response was found in corneal epithelial cells.ConclusionsThe expression of the TGFBI gene occurs in human corneal stromal cells but not in the corneal epithelial cells.This result might be of helpful for studying the function and role of TGFBI gene in pathogenesis of corneal dystrophy.

Background The human transforming growth factor beta-induced gene (TGFBI) is the first determined pathogenic gene to corneal dystrophy.But the molecular genetic mechanism is completely unknown.The study of concerning role of TGFBI is very important for us understand the physiological function of cornea,and the pathogenesis of corneal dystrophy.Objective The vector of human transforming growth factor beta-induced gene (TGFBI) in eukaryotic expression was constructed and transfected into the human corneal epithelial cells in order to explore its influence on the growth of human corneal epithelial cells.Methods Total RNA was extracted from normal donor cornea tissue and cDNA was obtained by reverse transcription.TGFBI cDNA was synthesized by reverse transcription-PCR and cloned into pCMV-N-HA vector and identified by sequencing with PCR and EcoRV,XhoI double restriction endonuclease.The cells were grouped into recombinant pCMV-N-HA-TGFBI plasmid group,pCMVN-HA plasmid group,non-transfected group and pGFP-C2 transfected group.The recombinant pCMV-N-HA-TGFBI plasmid was transfected to human corneal epithelial cells and identified by observing the expression of enhanced green fluorescence protein(EGFP) in the cells.The TGFBI mRNA and proteins were harvested from the cells for real-time PCR analysis and Western blot assay respectively in 58 hours after transfection.The growth of the transfected cells was assessed by Cell Counting Kit-8.The expressions of matrix metalloproteinase(MMP) and tissue inhibitors of matrix metalloproteinase (TIMP) proteins and their mRNA in transfected cells were detected using SYBR fluorescence realtime PCR analysis and Western blot assay.Results The sequencing result of pCMV-N-HA-TGFBI positive clone plasmid showed that amplified TGFBI eDNA inserted into the vector at the correct sequence.EGFP was expressed in transfected cells in 48 hours after transfer of pGFP-C2 with the transfer efficacy 70％.The expression intensity of TGFBI mRNA was significantly higher in recombinant pCMV-N-HA-TGFBI plasmid group compared with pCMV-N-HA plasmid group and non-transfected group,and TGFBI protein was expressed in recombinant pCMV-N-HA-TGFBI plasmid group.No significant difference was found in the A450value among recombinant pCMV-N-HA-TGFBI plasmid group,pCMV-N-HA plasmid group and non-transfected group ( F=3.34,P＞0.05 ).The mRNA level of MMP1,MMP3in the transfected cells was significant elevated but that of TIMP1 was declined in the recombinant pCMV-N-HA-TGFBI plasmid group compared with pCMV-N-HA plasmid group and non-transfected group (all P ＜ 0.05 ).Meanwhile,the expressions of MMP1,MMP3 and TIMP1 proteins appeared the same tendency( all P＜0.05).Conclusions Eukaryotic expression vector harboring human TGFBI eDNA can be successfully constructed and efficiently overexpressed in human corneal epithelial cells.TGFBI gene is involved in the physical and pathological conditions of human corneal epithelial cells by regulating the activity of MMP1,MMP3 and TIMP1.The results offer a new approach for the study of the role of TGFBI in pathogenesis of corneal transparency.

Polydatin is a monocrystaline compound isolated from Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae) with biological properties, such as anti-inflammation, anti-oxidative and nephroprotective effects. Increasing number of studies have demonstrated the protective effect of polydatin on renal ischemia reperfusion injury. However, the possible mechanisms of this protection are not fully elucidated. This study aimed to investigate the effect of polydatin on ischemia-reperfusion induced expression of toll-like receptor4 (TLR4) in rat renal tubular epithelia cells (NRK-52E), and analyze the mechanism of polydatin on TLR4 signal pathway. The cultured NRK-52E cells were incubated in three gas incubators for a period of 6 h at hypoxia and 24h at reoxygenation to simulate the ischemia-reperfusion injury in vitro. TLR4 mRNA level was analyzed by real-time-PCR, and the protein expression of TLR4 and NF-κB by Western blotting, while TNF-α and IL-1β proteins expressions were detected by ELISA. Polydatin downregulated I/R induced mRNA and protein expressions of TLR4, and decreased the protein expression of NF-κB, TNF-α and IL-1β. The TLR4 blocker partially antagonized the effect of I/R on NF-κB signaling, and such inhibitory effect was markedly enhanced by polydatin. In the present study, polydatin protects NRK-52E cells from I/R injury possibly by relieving the inflammatory response through regulation of TLR4/NF-κB signaling pathway.
Animals ; Cell Line ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Glucosides ; pharmacology ; Humans ; Rats ; Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Stilbenes ; pharmacology ; Toll-Like Receptor 4 ; genetics ; metabolism

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Antidepressive Agents ; chemical synthesis ; chemistry ; Biological Transport ; Drug Design ; Isoindoles ; chemical synthesis ; chemistry ; Serotonin Uptake Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

Professor YU Shu-zhuang is a distinguished acupuncturist in China. He has practiced the TCM acupuncture-moxibustion clinical, educational and scientific research for 60 years in his life. In clinic, he summarized the experiences "five-ming first"; in treatment, he insisted "dredging" and "regulating", protecting the function of spleen and stomach, and needles should be less but specific. In the meanwhile, he made a deep study on the function and clinical effects of specific acupoints, and used the research results of propagated sensation along channel to guide clinical treatment, forming his special academic points. Professor YU has educated a great number of acupuncture-moxibustion talents in China and foreign countries, making great contribution to the popularization of acupuncture-moxibustion in the worldwide.
Acupuncture ; education ; history ; Acupuncture Points ; Acupuncture Therapy ; history ; China ; History, 20th Century ; History, 21st Century