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Objective To observe the effects of total saponins of Trillium tschonoskii Maxim(TST)on vascular cognitive impairment(VCI),neurovascular units(NVUs),and neural circuit integrity in rats.Methods Forty-eight male Sprague-Dawley(SD)rats were randomly divided into sham-operated group,model group,TST group(intragastric administration,100 mg/kg),and donepezil group(intragastric administration,0.45 mg/kg),and then subjected to ischemic stroke by 2-VO method(bilateral common carotid artery ligation)or sham surgery.After 28 days of intragastric administration,Mirros water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group.HE and Nissl staining were used to observe the pathological changes of brain tissue in rats.The expression of synuclein(SYN)in rat hippocampus was observed by immunohistochemical staining.Changes in dendritic spines in rat's hippocampal neurons were observed by Golgi staining.Western blotting was used to detect the expression levels of IL-1β,IL-10,vascular endothelial growth factor A(VEGFA),postsynaptic density protein 95(PSD95),and growth associated protein 43(GAP43)in rat's hippocampus in each group.Results In Mirros water maze test,rats in model group showed significant prolonged escape latency(P<0.05),and a significant reduction in the number of crossing platforms and the percentage of activity time in the target quadrant(P<0.05)than those in sham-operated group;while rats in TST group and donepezil group showed significant shortened escape latency(P<0.01),and significant increase of the number of times of crossing platforms and the percentage of activity time in the target quadrant(P<0.05)than those in model group.Compared of sham-operated group,model group showed a decrease in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P<0.05).Compared with model group,TST group and donepezil group showed an increase in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P<0.05).Western blotting showed a significant increase in the expression of IL-1β and VEGF(P<0.05),and a decrease in the expression of IL-10,PSD95,and GAP43(P<0.01)in rat's hippocampus of model group than those in sham-operated group.Compared with model group,TST group and donepezil group showed a significant decrease in the expression of IL-1β(P<0.05),and an increase in the expression of VEGFA,IL-10,and GAP43(P<0.05).Conclusions TST could alleviate cognitive impairment through promoting synaptic plasticity and neurovascular unit remodeling in 2-VO model rats,suggesting its significance as a potential drug for apoplexy.
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Aim To investigate the effects of total saponins from Trillium tschonoskii maxim(TST)on cognitive impairment and mitochondrial autophagy in aging rats induced by D-galactose(D-gal). Methods Male SD rats were randomly divided into normal control group,model group(D-gal,subcutaneous injection),intervention group(TST,low,medium and high dose groups by intragastric administration),with 10 rats in each group,and administered for 6 weeks. Morris water maze was used to evaluate the cognitive function. HE and Nissl staining were used to test the hippocampal and brain cortex morphology. Immunohistochemistry staining was applied to detect the localization expression of Pink1 and Parkin. Western blot was employed to detect the expressions of Pink1,Parkin,LC3-Ⅱ,p62 and Beclin1. Results Compared with the normal control group,the escape latency time was prolonged and the number of crossing platform decreased in D-gal model group(P<0.05). The number of neurons in hippocampus significantly decreased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly decreased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 were markedly reduced,while the expression of p62 was significantly raised(P<0.05). Compared with D-gal model group,the escape latency time of TST dose groups was shortened,the Times of crossing the platform was more,and the time of staying in the platform quadrant increased(P<0.05). The number of neurons in hippocampus significantly increased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly increased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 in hippocampus were apparently up-regulated,while the protein expression of p62 was evidently down-regulated(P<0.05). Conclusions TST has neuroprotective effects on the learning and memory capacities in aging rats induced by D-gal,which may be related to the increasing levels of Pink1,Parkin,LC3-Ⅱ and Beclin1 proteins and the activation of mitochondrial autophagy.
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OBJECTIVES@#To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism.@*METHODS@#Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62).@*RESULTS@#Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 (P<0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group (P<0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 (P<0.05), and a significant increase in the protein expression level of P62 (P<0.05).@*CONCLUSIONS@#Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.
Subject(s)
Rats , Animals , Hypoxia-Ischemia, Brain/metabolism , Animals, Newborn , Rats, Sprague-Dawley , Beclin-1 , Autophagy , Ubiquitin-Protein Ligases/metabolism , Protein Kinases/metabolismABSTRACT
Programmed necrosis,a mode of cell death independent of Caspase,is mainly mediated by receptor-interacting protein kinase-1 (RIPK1),receptor-interacting protein kinase-3 (RIPK3),and mixed lineage kinase domain-like protein (MLKL).Studies have demonstrated that programmed necrosis has the dual role of promoting and inhibiting tumor growth and thus we can control the development of tumor by regulating programmed necrosis.The drugs capable of inducing programmed necrosis show potential anti-tumor activity.In addition,inducing programmed necrosis is an effective way to overcome tumor resistance to apoptosis.This paper summarized the mechanisms of programmed necrosis and its relationship with tumors.We focused on the antitumor activity of programmed necrosis inducers including natural products,chemotherapeutic drugs,death receptor ligands,kinase inhibitors,inorganic salts,metal complexes,and metal nanoparticles.These agents will provide new therapeutic candidates for the treatment of tumors,especially the tumors acquiring resistance to apoptosis.
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Humans , Apoptosis , Cell Death , Necrosis/pathology , Neoplasms/drug therapy , Protein Kinases/pharmacologyABSTRACT
@#Objectives , , To analyze occupational stress depressive symptoms anxiety symptoms and related influencing factors Methods among bus drivers in Urumqi. A total of 709 bus drivers in Urumqi were selected as the research subjects using - , - - judgment sampling method. The Effort Reward Imbalance Questionnaire Zung 's Self rating Depression Scale and Zung 's Self - ( ) , rating Anxiety Scale were used to investigate the occupational stress in the effort reward imbalance ERI mode depression and Results , anxiety symptoms of bus drivers. The detection rates of ERI mode occupational stress symptoms of depression and ( ), ( ) ( ), anxiety were 62.2% 441/709 30.2% 214/709 and 18.2% 129/709 respectively. The results of binary logistic regression , , analysis showed that education level length of service physical exercise and drinking were independent influencing factors of ( P ) occupational stress in ERI mode all <0.05 . Personal monthly income and physical exercise were the influencing factors ( P ), (P ) of depression symptoms all <0.05 and physical exercise was the influencing factor of anxiety symptoms <0.05 . Conclusion , The occupational stress depression and anxiety symptoms of bus drivers in Urumqi are serious. Attention should , , , be paid to people with higher education long working age low personal monthly income no physical exercise habits and drinking behavior to prevent occupational stress and mental health problems.
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In forensic traumatic pathology practice, immunohistochemistry and special staining technique play an important role in wound age estimation and complications of traumatic complication identification. They even play an important role in the identification of special cases, such as snakebites and insulin killings. This article reviews the application and value of immunohistochemistry and special staining techniques in forensic traumatic pathology based on the cases of forensic practice reported in literature.
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Forensic Medicine , Forensic Pathology/methods , Immunohistochemistry , Staining and LabelingABSTRACT
Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.
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Objective To design and synthesize a novel type of combined anti-tumor drug-doxorubicin modified silver nanoparticles(DOX-Ag NPs)with pH response,characterize its physical and chemical properties,and investigate its drug responsive release and anti-tumor activity in vitro.Methods DOX-Ag NPs were prepared by coupling silver nanoparticles (Ag NPs) with doxorubicin (DOX) via a LA-NHNH2linker. The structure of LA-NHN=DOX was confirmed by nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS).The particle size and micromorphology of the nanoparticles were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The optical properties of the nanoparticles were characterized by UV-vis absorption spectroscopy and fluorescence spectroscopy.The DOX release kinetics of DOX-Ag NPs under different pH conditions were examined by dialysis method combined with fluorescence spectroscopy. The in vitro anti-tumor effects of DOX-Ag NPs were evaluated by MTT assay. Results DOX-Ag NPs were spherical nanoparticles with a particle size of (40.4 ± 3.8) nm. DOX-Ag NPs could rapidly release DOX under weak acid condition.DOX-Ag NPs significantly inhibited the proliferation and cell viability of HepG2 cells in concentration dependent manner.When DOX concentration was 0.5-20 mg/L(Ag concentration was 0.45-18 mg/L), the cell survival rate was significantly lower in DOX-Ag NPs group than that of DOX group and Ag NPs group(P<0.05). Conclusion DOX-Ag NPs are a combined anti-tumor nano-drug with pH-responsive ability, which can release DOX rapidly in tumor tissues and play an anti-tumor effect through synergistic treatment with Ag NPs in vitro.
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<p><b>OBJECTIVE</b>To explore the effect and mechanism of Qingfei Mixture (), a Chinese medicine, in treating mycoplasma pneumonia (MP) in MP patients and rat model METHODS: A total of 46 MP children with phlegm heat obstructing Fei (Lung) syndrome were randomly assigned to two groups by the method of random number table, with 23 children in each group. The control group was treated with intravenous infusion of azithromycin; the treatment group received intravenous infusion of azithromycin and oral administration of Qingfei Mixture. The treatment course was 7 days. Major symptoms and minor symptoms were observed and scored before and after treatments. A rat model of MP was also established. A total of 120 wistar rats were randomly divided into 5 groups: a normal group, infection group, Qingfei Mixture treatment group, azithromycin treatment group, and Qingfei Mixture + azithromycin treatment group. Each group contained 24 rats, from which every 6 were euthanatized 1, 3, 7 and 14 days after infection. MP DNA in pulmonary tissue homogenates was detected using real-time fluorescence quantitative polymerase chain reaction. Pathology was assessed after hematoxylin (HE) staining and lung tissue pathology scores were determined in pulmonary tissue. Transmission electron microscopic detection and electronic image analysis were performed on lung tissue 3 days after infection. Interleukin (IL)-17 was detected in serum using enzymelinked immunosorbent assay (ELISA) 7 days after infection.</p><p><b>RESULTS</b>In the clinical study, both control and the treatment group showed improved results on removing symptoms of phlegm heat syndrome compared to the control group (P<0.05). In animal experiments, On the 7th day after MP infection, as detected by electron microscopy, the pulmonary capillary basement membranes of the azithromycin + Qingfei Mixture treatment group were much thinner than those of the azithromycin or Qingfei mixture treatment groups (P<0.05). The level of serum IL-17 in the azithromycin + Qingfei Mixture treatment group was lower than that in the azithromycin or Qingfei Mixture groups (P<0.01).</p><p><b>CONCLUSION</b>Both Qingfei Mixture and azithromycin have therapeutic effects on mycoplasma pneumoniae pneumonia, but the combination of both agents had the greatest effect.</p>
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AIM:To understand the clinic effect of intravitreal anti-vascular endothelial growth factor(VEGF) drugs injection in the treatment of fundus disease in the real-world study (RWS).METHODS:The clinical cases treated with anti-VEGF drugs in our department from September 2012 to June 2015 were enrolled in this study.Retrospective investigation was reviewed to the kinds of diseases, frequency, usage, efficacy, adverse reaction, and the effects on visual acuity, fundus and macular thickness which were treated with intravitreal anti-VEGF drugs injection.RESULTS:In 305 patients (340 eyes) treated with anti-VEGF drugs, 53 patients (60 eyes, 17.6%) were wet age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) 16 cases (18 eyes, 5.3%), diabetic macular edema (DME) 120 cases (134 eyes, 39.4%), branch retinal vein occlusion (BRVO) secondary macular edema 61 cases (68 eyes, 20.0%), central retinal vein occlusion (CRVO) secondary macular edema 29 cases (32 eyes, 9.4%), idiopathic choroidal neovascularization (ICNV) 16 cases (18 eyes, 5.3%), high myopia with choroid neovascularization 4 cases (4 eyes, 1.2%), neovascular glaucoma 4 cases (4 eyes, 1.2%), retinal angiomatous proliferation (RAP) 1 cases (1 eyes, 0.2%) and optic papillary neovascularization 1 cases (1 eyes, 0.2%).The minimum age was 16 years old, and the maximum age 90 years old.There were 247 cases (275 eyes, 80.9%) were treated with intravitreal ranibizumab injection, 58 cases (65 eyes, 19.1%) intravitreal conbercept injection.The time number of all patients accepted anti-VEGF drugs treatment was 465, with an average of 1.7 times per eye.Which, the 3 + PRN treatment method in 98 patients (109 eyes, 32.1%), 1 + PRN treatment in 207 patients (231 eyes, 67.9%).69 cases (77 eyes, 22.6%) were used alone to receive anti-VEGF drugs therapy, 10 cases (11 eyes, 3.2%) combined with intravitreal triamcinolone injection(TA), 35 cases (39 eyes, 11.5%) combined with vitrectomy, 26 cases (29 eyes, 8.5%) combined with photodynamic treatment (PDT), 165 cases (184 eyes, 54.1%) combined with simple laser treatment.After anti-VEGF drug treatment, majority of patients' the best corrected visual acuity (BCVA), fundus and central macular thickness(CMT) were significantly improved, compared with the pre-treatment, the difference is significant (P<0.05).So that anti-VEGF drugs can effectively improve visual function and ocular fundus for fundus diseses.There were no serious adverse reactions except 3 patients appearling skin redness, itching, rash, 1 patient low low-grade fever and 1 patient acute cerebral infarction during the treatment.CONCLUSION:Intravitreal anti-VEGF drugs injection can significantly improve the visual function and ocular fundus for patients with fundus diseases, but there are still some adverse events, which should be attached great importance to medical workers.
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EPSAH is an exopolysaccharide from Aphanothece halophytica GR02. The present study was designed to evaluate its toxicity and adjuvant potential in the specific cellular and humoral immune responses in ovalbumin (OVA) in mice. EPSAH did not cause any mortality and side effects when the mice were administered subcutaneously twice at the dose of 50 mg·kg(-1). Hemolytic activity in vitro indicated that EPSAH was non-hemolytic. Splenocyte proliferation in vitro was assayed with different concentrations of EPSAH. The mice were immunized subcutaneously with OVA 0.1 mg alone or with OVA 0.1 mg dissolved in saline containing Alum (0.2 mg) or EPSAH (0.2, 0.4, or 0.8 mg) on Day 1 and 15. Two weeks later, splenocyte proliferation, natural killer (NK) cell activity, production of cytokines IL-2 from splenocytes, and serum OVA-specific antibody titers were measured. Phagocytic activity, production of pro-inflammatory cytokines IL-1 and IL-12 in mice peritoneal macrophages were also determined. EPSAH showed a dose-dependent stimulating effect on mitogen-induced proliferation. The Con A-, LPS-, and OVA-induced splenocyte proliferation and the serum OVA-specific IgG, IgG1, and IgG2a antibody titers in the immunized mice were significantly enhanced. EPSAH also significantly promoted the production of Th1 cytokine IL-2. Besides, EPSAH remarkably increased the killing activities of NK cells from splenocytes in the immunized mice. In addition, EPSAH enhanced phagocytic activity and the generation of pro-inflammatory cytokines IL-1 and IL-12 in macrophages. These results indicated that EPSAH had a strong potential to increase both cellular and humoral immune responses, particularly promoting the development of Th1 polarization.
Subject(s)
Animals , Female , Mice , Rabbits , Adjuvants, Immunologic , Cyanobacteria , Chemistry , Immunity, Cellular , Immunity, Humoral , Immunization , Interleukin-12 , Allergy and Immunology , Interleukin-2 , Allergy and Immunology , Killer Cells, Natural , Allergy and Immunology , Mice, Inbred ICR , Ovalbumin , Allergy and Immunology , Polysaccharides , Allergy and Immunology , Th1 Cells , Allergy and Immunology , Th2 Cells , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>The purpose of this study was to set up a method to analyze the vertical semicircular canal function and study the normal values of the vertical semicircular canal function using the vertical plane swing test.</p><p><b>METHODS</b>A prospective analysis of 100 normal persons (aged from 18 to 59 years), who were treated by using the vertical plane swing test with the newly developed automatic vestibular function diagnosis and therapy system (SRM-IV). These persons were rotated 180° at a sinusoidal speed (acceleration 45°/s, maximum speed 90°/s) in the vertical semicircular canal plane. Using a PC, evoked vertical nystagmus was analyzed in order to evaluate the excitability of vertical semicircular canals, including the number and the duration of nystagmus, the slow phase velocity and other parameters. Meanwhile, the all persons were divided into two groups, order and younger than 45 years respectively. In the test procedure, with the two pairs of the right anterior vertical semicircular canal and left posterior vertical semicircular canal (RALP) as well as the left anterior vertical semicircular canal and the rear right vertical semicircular canals (LARP), the average slow phase velocity of the vertical nystagmus and the canal paresis (CP) of the two pairs of vertical semicircular canals were calculated using PC and SPSS13.0 software for statistical analysis.</p><p><b>RESULTS</b>There was no significant difference between the two groups (P > 0.05). The general CP of RALP was 10.2% ± 7.1%, and LARP was 10.4% ± 6.2%. The normal CP range of the vertical semicircular canal in the health group was identified (idea: ≤ 20%; normal high: 20% - 25%).</p><p><b>CONCLUSION</b>The 180° vertical plane sinusoidal swing method is effective in functional analysis of the vertical semicircular canal, it is expected to be reliably used in clinical treatment.</p>
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Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Reference Values , Semicircular Canals , Physiology , Vestibular Function Tests , Reference StandardsABSTRACT
<p><b>OBJECTIVE</b>To study the distribution and antibiotic resistance of gram-negative pathogens isolated from children with bronchopneumonia.</p><p><b>METHODS</b>The distribution and the results of susceptibility tests of 272 strains of gram-negative Bacillis isolated from children with bronchopneumonia during 2009 were analyzed.</p><p><b>RESULTS</b>Among the isolates, the common pathogens were Klebsiella pneumoniae and Escherichia coli. The extended-spectrum β-lactamase (ESBLs) production rate was 52.9%. Compared with the non-ESBLs producing strains, ESBLs-producing strains had a significantly higher drug resistance rate to many antibiotics except amikacin and meropenem (P<0.05). The lowest resistance to ESBLs producing gram negative strains was found for meropenem (0.7%), followed by imipenem, amikacin and cefoperazone/sulbactam.</p><p><b>CONCLUSIONS</b>More attentions should be paid to the high rate of drug-resistance of ESBLs producing strains in children. Antimicrobial therapy should be based on the results of drug resistance surveillance.</p>
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Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Bronchopneumonia , Drug Therapy , Microbiology , Drug Resistance, Microbial , Gram-Negative BacteriaABSTRACT
<p><b>BACKGROUND</b>Runt-related transcription factor 1 (Runx1) plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runx1 will induce leukemia and how the change of Runx1 expression level could affect BCR-ABL-induced leukemogenesis. In the present study, we aimed to analyze if abnormal expression of Runx1 in BaF3 cells alone would induce leukemogenesis. And we also wanted to know if abnormal expression of Runx1 in leukemic cells would affect leukemogenesis. Furthermore, we investigated whether overexpression or knock-down of Runx1 in BaF3 cells would induce leukemogenesis.</p><p><b>METHODS</b>Plasmids containing full-length Runx1 cDNA were transduced into BaF3 cells and BaF3-P185wt cells (BCR-ABL transformed BaF3 cells) by electroporation. Plasmids containing a short hairpin RNA of Runx1 were transduced into BaF3 cells and BaF3-P185wt cells by electroporation. Runx1 expression level was quantified by Western blotting and quantitative real-time PCR. The effects of overexpression or knock-down of Runx1 on proliferation, apoptosis and migration of cells were detected in vitro. Then, using MSCV-P185wt-EGFP as a control, we transplanted MSCV-P185wt-Runx1 cells or MSCV-P185wt-shRNA cells into Balb/c mice through tail vein and observed tumorgenesis of the different phenotypes.</p><p><b>RESULTS</b>In vitro analysis revealed that overexpression of Runx1 in P185wt cells could inhibit cell proliferation and slow down cell migration; while knock-down of Runx1 could promote cell proliferation and speed up cell migration. In vivo analysis indicated that mice transplanted with MSCV-P185wt-Runx1 survived longer than controls. In contrast, mice transplanted with MSCV-P185wt-shRNA survived shorter than the control group. Gross pathological analysis revealed that the MSCV-P185wt-Runx1 group had less severe splenomegaly and hepatomegaly compared to the control group, and the MSCV-P185wt-shRNA group had more severe splenomegaly and hepatomegaly. No splenomegaly or hepatomegaly was detected in mice transplanted with MSCV-BaF3-Runx1 cells or MSCV-BaF3-shRNA cells. Both the mice of MSCV-BaF3-Runx1 group and MSCV-BaF3-shRNA group were healthy with no sign of leukemia for up to three months.</p><p><b>CONCLUSIONS</b>Overexpression or knock-down of Runx1 gene in BaF3 cells alone could not induce leukemogenesis. However, in BaF3-P185wt cells, alteration of Runx1 expression could affect BCR-ABL-induced proliferation and migration in vitro and leukemogenesis in vivo.</p>
Subject(s)
Animals , Mice , Apoptosis , Blotting, Western , Cell Line , Cell Movement , Cell Proliferation , Core Binding Factor Alpha 2 Subunit , Genetics , Metabolism , Physiology , Fusion Proteins, bcr-abl , Pharmacology , Leukemia , Genetics , Metabolism , Pathology , Mice, Inbred BALB C , Polymerase Chain ReactionABSTRACT
<p><b>OBJECTIVE</b>To explore the relationship between metabolic syndrome and chronic kidney disease (CKD) in a rural adult population of Hunan province.</p><p><b>METHODS</b>1953 residents (older than 18 years) from the same village were randomly selected, using a stratified, multistage sampling method. All residents were interviewed and tested for albuminuria with morning spot urine albumin to creatinine ratio (abnormal: >/= 30 mg/g), reduced renal function with estimated glomerular filtration rate by modified MDRD equation [abnormal: < 60 ml/min (1.73 m(2))]. The associations of kidney damage indicators with demographic characteristics (age, gender, smoking status), indicators on health (diabetes, hypertension) and metabolic syndrome traits were examined.</p><p><b>RESULTS</b>Eligible data of 1709 subjects were enrolled in the study. After the adjustment of age, gender and other metabolic syndrome traits, participants with metabolic syndrome had a higher prevalence of CKD (19.3% vs. 13.2%, P < 0.001) than those without the syndrome. As the number of metabolic syndrome traits increased, so did the prevalence of CKD. There seemed to be a strong and independent association between metabolic syndrome and chronic kidney disease. For participants without hypertension and diabetes, metabolic syndrome was also associated with CKD (OR value 1.733, 95%CI: 1.20 - 2.41, P = 0.004).</p><p><b>CONCLUSION</b>In these 1709 adults under this study from a village of southern China, metabolic syndrome seemed to be associated with CKD.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , China , Epidemiology , Diabetes Mellitus , Epidemiology , Hypertension , Epidemiology , Metabolic Syndrome , Epidemiology , Prevalence , Renal Insufficiency, Chronic , Epidemiology , Risk Factors , Rural PopulationABSTRACT
<p><b>OBJECTIVE</b>To approach the incidence rate, symptoms, etiologies, correlating reasons, consequences and treatments of local responses caused by implant after cochlear implantation and to provide reference for the future works.</p><p><b>METHODS</b>From 1995 to 2007 there were 997 cases adopted cochlear implantation in Peding Union Medical College Hospital. Ten cases experienced local responses were analyzed retrospectively.</p><p><b>RESULTS</b>The incidence of local response was 1.003%. There were 6 males and 4 females. The ages were between 13 months to 8 years old. The average age was 34 months. The devices mainly were made by Cochlear and Med-EL companies. The mainly symptoms and signs were local swellings, complaint of pruritus after ear, decrease of sound legibility and so on. Onset frequencies of this disease was 1 to 8 times. The bacterium cultured of displacing liquids was negative. But the IgE was detected in 2 cases. Results showed the patients were midrange status of hypersensitivity. Positive conservative treatments must be done including antibiotics, antihistamines, necessarily using immunotherapy.</p><p><b>CONCLUSIONS</b>Besides local infection of bacteria, the allergy caused by silicone of implant coupled be a reason. Although the diagnose of this disease was difficult, but the screening of source of hypersensitivity was necessary before operation. It was recurrent attacks and maybe liable by kindred patients. Onset age was more below 4 years old. The patch test should be done again when the symptoms were occurrence after operation. If severe secondary infection was occurred and the states could not be well controlled the devices in the body must be explanted immediately. When the conditions were stable reimplantation could be experienced by non-sensibilisinogen devices.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Cochlear Implantation , Cochlear Implants , Hypersensitivity , Postoperative Complications , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To establish the method of recording auditory brainstem responses electrically stimulated via round-window niche in cochlear implants.</p><p><b>METHODS</b>Self-made platinum iridium alloy as a spherical electrode stimulation electrode, modified cochlear implants connected to in vitro speech processor as a electro-stimulator and evoke potential instrument for Bio-logic Navigator Pro, 17 cochlear implant patients with various ages and of different causes, including auditory neuropathy (2 cases), ossified cochlea (1 case), inner ear malformation (5 cases), leukodystrophy (1 case), unknown and reason (8 cases) were investigated during cochlear implant surgery. Before cochlear implantation, stimulation electrode was placed in the round-window niche while charge balanced biphasic constant current was used as electrical stimulation via round window niche, and then electrically evoked auditory brainstem response was recorded.</p><p><b>RESULTS</b>Electrically evoked auditory brainstem response waveforms were clearly recorded in all 17 cases. The latencies of III and V waves were (2.12 +/- 0.18) ms and (4.18 +/- 0.19) ms respectively, with threshold as (220.0 +/- 16.04) CL. The waveforms of the 2 patients with auditory neuropathy, 5 patients with inner ear malformation, 1 patient with ossified cochlea and 1 patient with leukodystrophy were well differentiated.</p><p><b>CONCLUSIONS</b>Monitoring electrically evoked auditory brainstem response was an objective nerve electrophysiological testing method that accurately reflects function completeness of auditory pathway. It had important value for helping making the judgment whether patients could acquire auditory response after cochlear implantation. This method was safe and gave high emission of auditory response, therefore should be spread widely.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Cochlear Implantation , Cochlear Implants , Electric Stimulation , Electrodes , Evoked Potentials, Auditory, Brain Stem , Physiology , Round Window, Ear , Physiology , Vestibulocochlear Nerve DiseasesABSTRACT
<p><b>BACKGROUND</b>Chinese tones are considered important in Chinese discrimination. However, the relevant reports on auditory central mechanisms concerning Chinese tones are limited. In this study, mismatch negativity (MMN), one of the event related potentials (ERP), was used to investigate pre-attentive processing of Chinese tones, and the differences between the function of oddball MMN and that of control MMN are discussed.</p><p><b>METHODS</b>Ten subjects (six men and four women) with normal hearing participated in the study. A sequence was presented to these subjects through a loudspeaker, the sequence included four blocks, a control block and three oddball blocks. The control block was made up of five components (one pure tone and four Chinese tones) with equiprobability. The oddball blocks were made up of two components, one was a standard stimulus (tone 1) and the other was a deviant stimulus (tone 2 or tone 3 or tone 4). Electroencephalogram (EEG) data were recorded when the sequence was presented and MMNs were obtained from the analysis of the EEG data.</p><p><b>RESULTS</b>Two kinds of MMNs were obtained, oddball MMN and control MMN. Oddball MMN was obtained by subtracting the ERP elicited by standard stimulation (tone 1) from that elicited by deviant stimulation (tone 2 or tone 3 or tone 4) in the oddball block; control MMN was obtained by subtracting the ERP elicited by the tone in control block, which was the same tone as the deviant stimulation in the oddball block, from the ERP elicited by deviant stimulation (tone 2 or tone 3 or tone 4) in the oddball block. There were two negative waves in oddball MMN, one appeared around 150 ms (oddball MMN 1), the other around 300 ms (oddball MMN 2). Only one negative wave appeared around 300 ms in control MMN, which was corresponding to the oddball MMN 2. We performed the statistical analyses in each paradigm for latencies and amplitudes for oddball MMN 2 in discriminating the three Chinese tones and reported no significant differences. But the latencies and amplitudes for control MMN in discriminating the three tones all were significantly different.</p><p><b>CONCLUSIONS</b>There are evident waveforms for oddball and control MMN obtained in normal hearing persons, indicating that the change of Chinese tones could be detected in the pre-attentive stage. Because control MMN can eliminate reflects for physical characteristics of sound, it is the genuine memory-based pre-attentive processing. Since control MMN can reflect the differences of Chinese tones processing better than oddball MMN, it is more sensitive in evaluating pre-attentive processing in Chinese tones discrimination.</p>
Subject(s)
Adolescent , Female , Humans , Male , Young Adult , Acoustic Stimulation , Methods , Auditory Perception , Physiology , China , Electroencephalography , Evoked Potentials , Physiology , Evoked Potentials, Auditory , Physiology , Hearing , Physiology , Language , Phonetics , Pitch Perception , Physiology , Reaction Time , PhysiologyABSTRACT
<p><b>BACKGROUND</b>It has been known that platelet activating factor receptors (PAFR) may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B (GB) possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment.</p><p><b>METHODS</b>Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow (rCBF, using (99m)Tc tracer technique), the brain water content (specific gravimetric method), PAFR (3H-labelled PAF assay), the respiratory control rate (RCR), the phosphorus-oxygen (P/O) ratio of mitochondrial respiration (Clark oxygen electrode), mitochondrial permeability transition (MPT) pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups (the ischemia group vs the sham group, and the ischemia group vs the GB group).</p><p><b>RESULTS</b>There were high affinity and low affinity sites for PAFR on the tree threws' brain cell membranes. The varying-affinity PAFR binding sites, the respiration state III, the state IV, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly (respectively, P < 0.01 and P < 0.05), but the water content increased (P < 0.01) in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB (5 mg/kg i.v.) 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated (P < 0.01) at 24h after cerebral ischemia. There were significant differences between the ischemia group and sham group (P < 0.01). In GB treated isolated neurons' mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed.</p><p><b>CONCLUSIONS</b>The activation of the PAFR may play an important role in the inhibition of the mitochondrial respiration and the induction of neuronal damage after cerebral thrombosis; however, GB possesses neuroprotective effects by improving mitochondrial metabolism.</p>
Subject(s)
Animals , Female , Male , Brain Ischemia , Drug Therapy , Metabolism , Pathology , Ginkgolides , Therapeutic Uses , Lactones , Therapeutic Uses , Mitochondria , Metabolism , Neuroprotective Agents , Therapeutic Uses , Oxygen Consumption , Platelet Activating Factor , Platelet Membrane Glycoproteins , Receptors, G-Protein-Coupled , TupaiidaeABSTRACT
<p><b>BACKGROUND</b>In vitro fertilization (IVF) researches have suggested that cystathionine beta synthase (CBS) is involved in oocyte development. However, little is known about the regional and cellular expression patterns of CBS in the ovary. The purpose of this study was to analyze the localization of CBS in mice ovaries and to investigate the expression profile during follicular development.</p><p><b>METHODS</b>We used in situ hybridization and immunohistochemical analysis to determine CBS expression in the ovaries of female Balb/c mice. Then the follicles were collected from F1 (C57BL x Balb/c) mice and cultured in vitro. With the method of semi-quantitative RT-PCR, we also investigated the expression profile of CBS during follicular development.</p><p><b>RESULTS</b>CBS was absent in the oocytes, although it was ubiquitously expressed in the ovary with the strongest expression in follicular cells at all stages. In late antral follicles, CBS expression was markedly higher in granulosa cells located close to the antrum and in cumulus cells around the oocyte. The semi-quantitative RT-PCR showed that CBS mRNA was detected in follicles at all stages in vitro. In cumulus-oocyte complexes superovulated, CBS expression also increased rapidly.</p><p><b>CONCLUSIONS</b>CBS was located mainly in the follicular cells in the ovaries. The level of CBS expression is high in follicles during folliculogenesis in mice. Differences in the CBS expression profile between oocyte and follicular cells suggest a role for CBS as a mediator in interactions between oocyte and granulosa cells.</p>