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Objective: This study explored the thromboembolism risk of low-risk atrial fibrillation (AF) patients (CHA2DS2-VASc score of 0 or 1 for male and 1 or 2 for female) with different clinical characteristics to provide the basis for anticoagulation decision-making in these patients. Methods: We prospectively enrolled consecutive 2 862 nonvalvular low-risk AF patients between August 2011 to December 2018 in China-AF (China Atrial Fibrillation Registry) Study, their CHA2DS2-VASc score was 0 or 1 for male and 1 or 2 for female. According to their age, sex, presence or absence of hypertension, diabetes mellitus, congestive heart failure, and vascular disease at the time of enrolling, patients were divided into CHA2DS2-VASc score 0 score group, 1 score group, and 2 score group. Patients were followed up every 6 months by outpatient clinic visit or telephone interview. The outcome was a thromboembolic event, including ischemic stroke and systemic embolism. Univariate Cox regression analysis was used to compare the thromboembolism risk between the patients with different risk factors and CHA2DS2-VASc score 0 group. Results: A total of 2 862 low-risk atrial fibrillation patients were enrolled in this study. 915 patients (32.0%) were female, and age was (55.0±10.7) years old. There were 933 patients (32.6%) in CHA2DS2-VASc score 0 group, 1 401 patients (49.0%) in score 1 group and 528 patients (18.5%) in score 2 group. During follow-up (median 1.5 years, 5 811.82 person-years), 33 cases of thromboembolic events were recorded, the annual rate of thromboembolism was 0.57% (95%CI 0.40%~0.80%). The number of thromboembolic events in patients with CHA2DS2-VASc score 0, 1 and 2 were 8, 11 and 14, respectively, and the annual thromboembolism event rates were 0.40% (95%CI 0.20%-0.81%), 0.39% (95%CI 0.22%-0.71%) and 1.34% (95%CI 0.80%-2.27%), respectively. The risk of thromboembolism of CHA2DS2-VASc score 2 group (HR=3.53, 95%CI 1.48-8.44; P=0.005), especially female patients aged 65-74 years in CHA2DS2-VASc score 2 group (HR=2.67, 95%CI 1.63-4.38; P<0.000) was significantly higher than that in patients of CHA2DS2-VASc score 0 group. Conclusion: Low-Risk Atrial Fibrillation patients with CHA2DS2-VASc score 2, especially female patients aged 65-74 years old with CHA2DS2-VASc score 2 are at higher risk of thromboembolism in low-risk AF patients. For such patients, intensified oral anticoagulant therapy might be helpful to reduce the risk of thrombolism.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Anticoagulants , Atrial Fibrillation , China , Risk Assessment , Risk Factors , Stroke , ThromboembolismABSTRACT
To investigate the relationship between anti-depressant effect and hippocampal nerve growth of Xiaoyao San,the inflammatory model of hippocampal neuron was induced by lipopolysaccharide( LPS). The effect of Xiaoyao San serum( final concentration of4%,8%) on the cell proliferation activity was detected by immunofluorescence,the levels of BDNF and β-NGF in the supernatant of hippocampal neurons were detected by ELISA,and the expressions of BDNF,NGF,Trk B,Trk A and CREB mRNA in cell lysate of hippocampal neuron were detected by PCR. Western blot was used to detect the expressions of Trk B,CREB,p-CREB and SYP protein in cell lysate of hippocampal neuron,and to reveal the neuroprotective effect and mechanism of Xiaoyao San. The results showed that8% Xiaoyao San serum could significantly increase in Brdu/Neu N ratio( P<0. 01). 4%,8% Xiaoyao San serum could significantly improve the levels of BDNF and β-NGF in supernatant( P<0. 05 or P<0. 01),up-regulate the expression of BDNF,NGF,Trk B,Trk A,CREB mRNA and Trk B,p-CREB,SYP protein in cell lysate( P< 0. 05 or P< 0. 01). 8% Xiaoyao San serum could significantly increase CREB protein in cell lysate( P<0. 05),and elevate in p-CREB/CREB ratio( P<0. 01). All the above results indicate that Xiaoyao San has a certain protective effect on LPS induced hippocampal neuron injury,which suggests that the protective effect of Xiaoyao San is related to the promotion of hippocampal nerve growth,which is one of its antidepressant mechanisms.
Subject(s)
Brain-Derived Neurotrophic Factor , Drugs, Chinese Herbal , Hippocampus , Lipopolysaccharides , NeuronsABSTRACT
The LPS-induced RAW264. 7 cells inflammation model was used as a carrier to investigate the in vitro anti-inflammation effects of Jingfang n-butanol extraction(JFNE) isolated fraction A and explore its preliminary anti-inflammation mechanism by observing the regulatory effect on PI3 K/AKT signaling pathway and NF-κB pathway. The RAW264. 7 cells inflammation model was established by stimulating with LPS for 12 h. After 3 h pre-treatment with fraction A,the contents of interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor(TNF-α) in the supernatant of RAW264. 7 cells inflammation model were determined by ELISA and the contents of NO in supernatant were assayed by Griess. Reverse transcription-polymerase chain reaction(RT-PCR) method was used to determine the expression of IL-6,IL-1β,TNF-α,IFN-γ,i NOS,PI3 K,AKT,CHUK,NF-κB1 and Rela mRNA in RAW264. 7 inflammatory cells,and the expression levels of phosphorylated and total PI3 K/AKT protein,NF-κB p50,p65,p-p65,p105 protein in cells were determined via Western blot. In addition,LC-MS and database were used to identify the possible chemical constituents in fraction A. The results showed that fraction A could significantly reduce the release levels of NO,IL-6,IL-1β and TNF-α in the supernatant and the expression of IL-6,IL-1β,TNF-α,IFN-γ,i NOS,PI3 K,AKT,CHUK,NF-κB1 and Rela mRNA in RAW264. 7 inflammation model cells(P<0. 05 or P<0. 01) and significantly inhibit the phosphorylation expression levels of PI3 K and AKT protein and mRNA expressions(P<0. 05 or P<0. 01). Moreover,fraction A could significantly reduce the levels of NF-κB p50,p-p65 and i NOS protein,as well as NF-κB1,Rela mRNA expressions in RAW264. 7 cells,and increase the expression of CHUK gene.A total of 196 compounds were identified from fraction A in the composition analysis,and isoobtusilactone,5-O-methyl-vismitol,emebel(embelin) and prim-O-glucosylcimifugin showed high contents. The results all above showed that fraction A had a certain antiinflammatory effect in LPS-induced RAW264. 7 inflammation model cells,and its anti-inflammatory effects may be related to its regulatory effect on the activation of PI3 K/AKT signaling pathway and NF-kappa B signaling pathway. In addition,emblin may be its effective anti-inflammation chemical composition.
Subject(s)
Animals , Mice , 1-Butanol , Drugs, Chinese Herbal , Pharmacology , Inflammation , Interleukin-1beta , Metabolism , Interleukin-6 , Metabolism , Lipopolysaccharides , Macrophages , Plant Extracts , Pharmacology , Signal Transduction , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
Objective: To investigate the effect and mechanism of Xiaoyaosan on lipopolysaccharide(LPS)-induced nerve injury. Method: The 56 rats were randomly divided into control group, sham group, model group, amitriptyline group (10 mg·kg-1), fluoxetine group (10 mg·kg-1), Xiaoyaosan group high and low-dose (30,15 g·kg-1).The nerve injury model rat were established by LPS injection into lateral ventride, rats were administrated for 14 days by gavage. The levels of brain-derived neurotrophic factor (BDNF) and β-nerve growth factor (β-NGF) in serum were detected by enzyme linked immunosorbent assay(ELISA), and the expressions of BDNF, nerve growth factor (NGF), tropomyosin receptor kinase B (TrkB), tropomyosin receptor kinase A (TrkA), cAMP response element-binding protein (CREB) mRNA in hippocampus and cortex were detected by Real-time PCR.Protoin expression of BDNF, TrkB, CREB, p-CREB, postsynaptic density protein 95 (PSD95), synaptophysin (SYP) in hippocampus and cortex were detected by Western blot. Result: Compared with control group, LPS decreased the level of BDNF and β-NGF in serum(PPPβ-NGF in serum in Xiaoyaosan high and low-dose group were increased significantly (PPPPConclusion: Xiaoyaosan has a certain antagonistic effect on LPS inducednerve injury, which suggests that the effect is related to activate BDNF/NGF-TrkB/TrkA-CREB pathway and upregulated the expression of synaptic protein.
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Purpose To investigate the clinicopathologic characteristtics, immunophenotype and differential diagnosis of uterine adenosarcoma with sarcomatous overgrowth. Metheds The clinicopathological data of 4 cases of uterine adenosarcoma with sarcomatous overgrowth were collected, the histopathologic and immunohistochemical features were investigated, and the rele-vant literatures were also reviewed. Results All of tumors were arised from the endometrium with complains of postmenopausal vaginal bleeding or prolonged menstrual period. There is a poly-poid nodular in the uterine cavity with a pedicle or no pedicel, or rough endometrium. On the cut surface, the tumor was fish-like without distinct from the surrounding tissue. Light microsco-py show the tumors were composed of benign glands and malignant mesenchymal components, the sarcomatouscomponents ac-counted for over 25%. In 4 cases, 2 cases had heterologous com-ponent of rhabdomyosarcoma. The component of sarcomatous were positive for vimentin and CD10. The heterologous component of rhabdomyosarcoma were positive for desmin, MyoDl, and Myogenin.3 cases were died at in 5, 10, and 19 months after operation, 1 patient was disease free survival for 3 months. Conclusion Uterine adenosarcoma with sarcomatous overgrowth has a bad prognosis.
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PURPOSE: Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. MATERIALS AND METHODS: Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg.kg-1.d-1) and high-dose darapladib (50 mg.kg-1.d-1) interventions were then administered over the course of 2 weeks. RESULTS: The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p0.05). CONCLUSION: Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.
Subject(s)
Animals , Male , Rats , 1-Alkyl-2-acetylglycerophosphocholine Esterase/antagonists & inhibitors , Atherosclerosis/blood , Benzaldehydes , C-Reactive Protein/metabolism , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dose-Response Relationship, Drug , Oximes , Phospholipase A2 Inhibitors/administration & dosage , Rats, Sprague-Dawley , Triglycerides/blood , rho-Associated Kinases/metabolismABSTRACT
ObjectiveTo investigate the effect of drinking brick tea with low-fluoride level on prevention of tea type fluorosis.MethodsHandahangacha,Hadayinggegacha,Dalainuoyi town,in Keshiketengqi Inner Mongolia endemic fluorosis area were selected as test points,and brick tea with fluoride [(204.5 ± 10.2),(308.2 ±15.4)mg/kg] was given for 12 months.Dental fluorosis,clinical skeletal fluorosis,and X-ray diagnosis of skeletalfluorosis [according to “Endemic Skeletal Fluorosis Diagnostic Criteria” (WS 192-2008)] of adults 20 to 70 years of age were examined and level of fluoride before and after the prevention trial,in brick tea,drinking water,milk tea and urine were tested (fluoride ion selective electrode method),and fluoride intake through tea was calculated.ResultsDetection rate of adult dental fluorosis in Handahangacha was 68.89% (62/90),clinical detection of skeletal fluorosis was 55.32% (52/94),and X-ray detection of skeletal fluorosis was 65.17% (58/89); adult dental fluorosis detection rate in Hadayinggegacha was 54.84%(51/93),clinical detection of skeletal fluorosis was 65.69%(67/102),and X-ray detection rate of skeletal fluorosis was 61.36% (54/88).Brick tea fluoride was (831.4 ±138.9),(864.3 ± 134.6)mg/kg before the prevention trial in Handahangacha and Hadayinggegacha,respectively,drinking water fluoride content was (0.27 ± 0.05),(0.54 ± 0.24)mg/L,fluoride content of milk tea was (216 ± 1.12),(2.82 ± 1.38)mg/L,adult urine fluoride content was (2.78 ± 1.57),(2.96 ± 1.80)mg/L,and fluoride intake through milk tea was (8.12 ± 5.84),(6.42 ± 5.04)mg/d,respectively; after the prevention trial the fluoride content of brick tea was (204.5 ± 10.2),(308.2 ± 15.4)mg/kg,fluoride content of drinking water (0.34 ± 0.11),(0.62 ± 0.30)mg/L,fluoride content of milk tea(0.97 ± 0.33),(1.83 ± 0.66)mg/L,fluoride content in urine(1.29 ± 0.55),( 1.47 ±0.62)mg/L,fluoride intake through milk tea (3.45 ± 2.05),(3.71 ± 2.07)mg/d,respectively; in Handahan and Hadayinggegacha after the prevention trial the fluoride in brick tea,milk tea,urine fluoride,and fluoride intake through milk tea was significantly lower than that before the trial (t =14.30,12.97 ;6.46,3.95;6.69,5.72;6.27,3.57,all P < 0.01 ).Fluoride intake in Handahangacha through milk tea was within the state heath standard limits( < 3.5mg/d).ConclusionDrinking low-fluoride brick tea can prevent drinking brick tea type fluorosis,the preventive effect is especially more reliable with low fluoride brick tea (204.5 ± 10.2)mg/kg.
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<p><b>OBJECTIVE</b>To investigate whether a simulated He-O2 saturation dive to 65 msw would affect oxidative balance in humans.</p><p><b>METHODS</b>Seven divers participated in a simulated saturation dive to 0.75 MPa (65 msw). 24-h urine samples were collected twice before, twice during, and twice after the dive, then were analyzed for contents of superoxide dismutase (SOD), malondialdehyde (MDA), total amino acid (T-AA) and total anti-oxidant capacity (T-AOC). Meanwhile, total urine volume and body weight were measured.</p><p><b>RESULTS</b>The content of T-AA was higher. (P < 0.05) than the base value in final decompression, but reverse to normal at one week after decompression. There were no changes in contents of SOD, MDA and T-AOC during and after the dive compared with their basic value. Total urine volume was lower (P < 0.05, vs basic value) at first day in chamber, then returned to normal. Body weight gradually increased after compression till the end of decompression (higher than basic value, P < 0.05).</p><p><b>CONCLUSION</b>These data indicate that simulated saturation dive to 65 msw may not induce obvious oxidative damage, but it is necessary to monitor 24-h urine volume and oxidative sress by time in order to prevent from tissue injury.</p>
Subject(s)
Adult , Humans , Male , Amino Acids , Urine , Decompression , Diving , Physiology , Helium , Chemistry , Malondialdehyde , Urine , Oxidative Stress , Physiology , Oxygen , ChemistryABSTRACT
Objective To observe the absorption, excretion and retention of fluoride and aluminum after drinking brick tea in healthy adults. Methods The study was conducted in ten healthy volunteers by drinking brick tea solution in which the fluoride and aluminum concentrations were 5.97, 7.53 mg/L, respectively. The concentrations of fluoride and aluminum were determined in serum samples collected before and at 0.5,1.0,2.0,3.0,and 24.0 h, and in urine samples collected before and during the periods 1.0,2.0,4.0, > 4.0 - < 24.0 h and 24 h after drinking brick tea solution by ion-selective electrode, inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma atomic mess spectrometry. The total amounts of intake and excretion of fluoride and aluminum in healthy volunteers during 24.0 h were calculated from their corresponding fluoride and aluminum ingesting from brick tea and excreting from urine. Results Before and during the periods 1.0,2.0,4.0,> 4.0 - < 24.0 h and 24.0 h after drinking brick tea solution, the urinary fluoride concentrations were (0.50 ±0.14), (2.14 ± 0.90), (1.57 ± 0.93), (2.43 ± 1.49), (1.91 ± 0.69), (0.58 ± 0.20)mg/L, respectively, and the aluminum concentrations in the urine samples were (0.35 ± 0.15), (0.65 ± 0.37), (0.50 ± 0.25), (0.52 ± 0.21 ),(0.50 ± 0.23), (0,46 ± 0.27)mg/L, respectively; the 24.0 h excreting rates of fluoride and aluminum from urine were 52.90%(4.64/8.77) and 12.38% (1.37/11.07), respectively. The fluoride concentrations in serum samples collected before and at 0.5,1.0,2.0,3.0,24.0 h after drinking brick tea solution were (0.06 ± 0.02), (0.14 ± 0.01 ), (0.21 ±0.04), (0.17 ± 0.04), (0.10 ± 0.03), (0.04 ± 0.01 )mg/L, respectively, and aluminum in those were (0.30 ± 0.05),(0.27 ± 0.01 ), (0.30 ± 0.12), (0.34 ± 0.19), (0.30 ± 0.10), (0.27 ± 0.09)mg/L, respectively. Conclusions Fluoride in brick tea is easyly to be absorbed and excreted through kidney, and the kidney excretory capacity of aluminum in brick tea is limited. Levels of fluoride and aluminum in urine could be taken as the indicators for monitoring the prevalent extent and evaluating preventive experiment's effect on the brick tea fluoride-aluminum toxicity; and fasting serum fluoride and aluminum levels could be taken as indicators for estimating the toxic condition of the brick tea fluoride-aluminum toxicity.