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Objective:To explore the correlation between platelet distribution width (PDW) and the stability of warfarin anticoagulant therapy in patients with persistent atrial fibrillation.Methods:138 patients with persistent atrial fibrillation treated with warfarin in Jiujiang First People′s Hospital from January 2018 to December 2019 were selected. They were divided into groups according to whether PDW increased (PDW decreased group, normal group, PDW increased group) and subgroups stratification was performed. After stratification, the relationship between PDW and the stability of warfarin anticoagulation treatment [expressed as the percentage of time of International normalized ratio(INR) within the treatment target range (TTR)] was analyzed. At the same time, the predictive value of PDW for the stability of warfarin anticoagulation treatment was analyzed.Results:There were significant difference in PDW and TTR among the PDW decreased group, normal group, PDW increased group ( F=30.322, 10.745, all P<0.01). The PDW distribution of patients with different anticoagulation quality was significantly different (χ 2=9.532, P<0.05). Receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of PDW in predicting warfarin anticoagulant stability was 0.621(95% CI: 0.524-0.737). There was significant difference in PDW and TTR among the PDW<14%, 14%-<16%, 16-<18% and ≥18% groups( F=18.075, 11.638, all P<0.01). There was no significant difference in PDW and TTR among the three subgroups of PDW<14%, 14%-<16% and 16-<18% ( P=0.843, P=0.401). There were significant difference in PDW and TTR between the two subgroup of PDW 16-<18%、≥18% ( t=4.154, 6.712, all P<0.01). Conclusions:PDW is correlated with the standard rate of warfarin anticoagulant stability, and can be used to predict the standard rate of warfarin anticoagulant stability.
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Rapid detection and response to visual threats are critical for survival in animals. The amygdala (AMY) is hypothesized to be involved in this process, but how it interacts with the visual system to do this remains unclear. By recording flash-evoked potentials simultaneously from the superior colliculus (SC), lateral posterior nucleus of the thalamus, AMY, lateral geniculate nucleus (LGN) and visual cortex, which belong to the cortical and subcortical pathways for visual fear processing, we investigated the temporal relationship between these regions in visual processing in rats. A quick flash-evoked potential (FEP) component was identified in the AMY. This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC, which was assumed to be an important area in visual fear. This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection, but was diminished by RU38486, a glucocorticoid receptor blocker. By injecting a monosynaptic retrograde AAV tracer into the AMY, we found that it received a direct projection from the retina. These results confirm the existence of a direct connection from the retina to the AMY, that the latency in the AMY to flashes is equivalent to that in the sensory thalamus, and that the response is modulated by glucocorticoids.
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@#This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.
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Objective:To explore the value of magnetic resonance diffusion kurtosis imaging (DKI) in the early diagnosis of Parkinson′s disease (PD).Methods:Thirty patients with early PD who were admitted to the Fujian Medical University Union Hospital From December 2016 to September 2017 were selected as case group, and 20 healthy persons in the same period were selected as healthy control group. 3.0 T GE magnetic resonance DKI was used to analyze olfactory related brain regions of the case group and the control group, the statistical differences were compared between the two groups in fractional anisotropy (FA), mean diffusion (MD), mean kurtosis (MK) values of olfactory cortex, and the correlation between MK values of olfactory cortex of the case group and age, disease course, Hoehn-Yahr (H-Y) stage, olfactory test, cognitive function evaluation was analyzed. Receiver operating characteristic (ROC) curve was used to determine the best diagnostic cutoff value of olfactory cortical MK in PD.Results:The left amygdala MK between the PD group (0.595±0.037) and the control group (0.647±0.091) showed statistically significant difference ( t=-2.183, P=0.037). ROC curve was drawn according to the MK value of the left amygdala of the PD group: the best diagnostic cutoff value was 0.597, the sensitivity was 65.0%, and the specificity was 52.2%. There was a statistically significant difference between the PD group and the control group in Montreal Cognitive Assessment (MoCA; 21.03±3.71 vs 24.25±1.65, t=-3.636, P=0.001) and Frontal Assessment Battery (FAB) scores (13.93±1.36 vs 15.00±1.25, t=-2.086, P=0.042), and there was negative correlation between MoCA, FAB scores and H-Y stage ( r=-0.548, P=0.007; r=-0.465, P=0.025). There was a positive correlation between MK value of the right direct gyrus of the PD group and MoCA evaluation results ( r=0.447, P=0.032). Conclusions:The left amygdala DKI can be used as a biomarker of PD in the early stage, which is helpful for the early diagnosis of PD. MoCA and FAB scales can be used as tools to monitor the progress of PD cognitive impairment. PD cognitive dysfunction may be related to impairment of frontal lobe function.
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Objective:To investigate the effect of microRNA-124 (miR-124) expression on pathological changes of Tau in elderly patients with Alzheimer disease to provide a new target for early detection and early treatment of Alzheimer disease in the elderly.Methods:The serum of 50 patients with Alzheimer disease from June 2017 to June 2018 in the Third People′s Hospital of Qinghai Province Hospital was taken as the sample of the research group and the serum of 50 healthy people was taken as the control sample. The mRNA expression of miR-124 in serum was determined by real-time polymerase chain reaction. The double antibody sandwich enzyme-linked immunosorbent assay was used. The expression levels of Tau protein and phosphorylated Tau (PTau) protein (S396, T181 and T231) were examined; pathological changes of Tau protein were detected by positron emission tomography.Results:The mRNA expression of serum miR-124 in Alzheimer disease patients was significantly higher than that in the control group (6.91 ± 0.41 vs. 5.11 ± 0.37, P < 0.01). The expression levels of total Tau protein, PTau (S396) protein and PTau (T181) protein in Alzheimer disease patients was significantly up-regulated, compared with those of the control group: (195.16 ± 20.48) ng/L vs. (123.25 ± 20.26) ng/L, (69.35 ± 8.92) ng/L vs. (40.53 ± 4.36) ng/L, (66.83 ± 8.45) ng/L vs. (35.87 ± 2.18) ng/L, P < 0.05. The pathological changes of Tau protein were clinically manifested as brain deposition, and the main parts were frontal lobe, occipital lobe, parietal lobe and temporal lobe. The overexpression of miR-124 was positively correlated with high expression of PTau (S396), high expression of PTau (T181) and high expression of total Tau, and it was an independent influencing factor. Conclusions:Overexpression of miR-124 can promote the expression of total Tau protein and phosphorylation of Tau protein, which is clinically indicative of Tau protein deposition in the brain of Alzheimer disease patients. It is expected to be a prognostic biomarker for Alzheimer disease.
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Objective To investigate the diagnostic value of quantitative detection of α-synuclein and DJ-1 protein in saliva for Parkinson Disease. Methods Twenty seven patients diagnosed with primary Parkinson's disease and 27 healthy controls were studied.The clinical data of all subjects were collected.Each participant received a disease evaluation including Hohn-Yahr stage, unified Parkinson Disease Rating Scale (UPDRS)-Ⅱ / Ⅲ, 12 Item odor identification test from Sniffin'Sticks (SS-12), Montreal cognitive assessment (MoCA), Mini Mental State Examination (MMSE).α-syn and DJ-1 protein in saliva were examined by using enzyme linked immunosorbent assay (ELISA). The statistical analysis was used to test the difference in these two protein levels between patient and control groups and the correlation with age, gender and course of disease. Results There were significant changes in mean concentration of salivary α-syn (1269.02±16.09 pg/mL、1350.51±25.79 pg/mL,P=0.010) and DJ-1 protein (6.07±3.23 ng/mL、8.43±4.33 ng/mL,P=0.027) between patient and control groups. The sensitivity of α-syn and DJ-1 protein levels in PD diagnosis was 55.56% and 77.8%,and the specificity was 89.19% and 55.6%.The area under the ROC curve in finding the PD of α-syn and DJ-1 was 0.671 and 0.649, respectively. In Parkinson disease group, age, gender, UPDRS-Ⅱ / Ⅲ, Hohn-Yahr stage, SS-12, MMSE and MoCA of Parkinson's disease group were not related to the concentration of α-syn and DJ-1 protein in saliva (P>0.05). Conclusion The detection of α-syn and DJ-1 protein levels in saliva may be an auxiliary tool for diagnosis of PD.
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Objective To investigate the changes of plasma free carnitine (FC) concentrations in preterm infants supplemented with L-carnitine, and to provide a reference for routine preterm infants L-carnitine supplements. Methods A total of 99 preterm infants supplemented with 10 mg/(kg·d) L-carnitine on days 2 and 5 after birth, and 65 full term infants from Department of Neonatology, the Fifth People′s Hospital of Dongguan during July 2014 to December 2015 were recruited in this study , and filter-paper blood spots were collected by heel prick on days 1, 3 and 7. FC was measured using electron spray ionization (ESI) tandem mass spectrometry (MS-MS). Results Concentrations of FC decreased steadily from day 1 to day 7 in full term infants , while it remained the same level during the first week after birth as at birth. Additionally, concentrations of FC were significantly higher in preterm infants than full term infants on day 1 after birth. Conclusions The reasonable L-carnitine supplements may keep the levels of plasma FC at the levels at birth , which is important for fatty acid metabolism in preterm infants.
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The author analyzed how toelaborate narrative contents using structured standard with electronical -ly structured medical record information model and the relation of the two .Astructured medical record data entry way was worked outcompatible with standard terminology based on ways of expressing narrative contents using structured standard.It provided a theoretical basis for clinical use .
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Objective To explore the protective effect and underlying mechanism of telmisartan on hyperuricemic nephropathy.Methods (1)High level of uric acid (600 μmol/L) and telmisartan in different concentrations (10nmol/L,100 nmol/L,1000 nmol/L,10000 nmol/L) were added to renal tubule epithelial cells and cultured for 48 h,the expression of UAT,TGF-β1 and α-SMA were detected by Real-time PCR,RT-PCR,Western blotting or cell immunofluorescence.(2) Wister rats were randomly divided into normal control group(Con),high uric acid group (HU),and telmisartan treatment group (Tel).Four weeks later,Scr,BUN and serum uric acid of the rats were detected.The expression of UAT in rat kidney was detected by Western blotting.Results (1)In vitro,compared to control group,high uric acid (600 μmol/L) inhibited the expression of UAT (P ＜ 0.01),and the inhibition could be alleviated by telmisartan; Telmisartan inhibited the upregulation of TGF-β1 and α-SMA induced by high uric acid(all P ＜ 0.05); (2)In vivo,compared to high uric acid group rats,telmisartan group rats had significantly reduced serum uric acid levels (189.9 μmol/L vs 204.5 μmol/L,P＜0.05),upregulated UAT and downregulated TGF-β1 expression in rat kidney (all P＜ 0.05).Conclusion Telmisartan significantly inhibits the upregulation of TGF-β1 and α-SMA induced by uricemia,which may prevent kidney from fibrosis.The protect effect of telmisartan may be related to the upregulation of UAT.
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The aim of this study was to establish the methods to identify crystal form of dasatinib in tablets.X-ray powder diffraction(XRPD)and solid-state nuclear magnetic resonance(ssNMR)were used to analyze the crystal form of dasatinib in Sprycel? tablets and Yinishu? tablets.The results showed that monohydrate and anhydrate were identified in Sprycel? and Yinishu? tablets respectively;with no detectable anhydrate in Sprycel? tablets and no detectable monohydrate in Yinishu? tablets.The results of XRPD and ssNMR were consistent;and could be both applied in the crystal form identification of dasatinib in tablets.
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Objective: To study therapeutic effects of simvastatin on vascular endothelial cell dysfunction in patients with coronary heart disease (CHD). Methods: According to LDL-C level, a total of 90 CHD patients were divided into simvastatin 20mg group (n=37, LDL-C≥2.5mmol/L), simvastatin 10mg group (n=35, 1.8mmol/L≤LDL-C0.05 all; Compared with routine treatment group, there were significant improvement in FMD [(6.01±0.49)% vs. (9.01±0.39)% vs. (9.01±0.47)%，P0.05 all. Conclusion: Simvastatin can increase NO concentration and improve vascular endothelial cell dysfunction in CHD patients. Its mechanism may be related with lipid-lowering effect, but independent of its lipid-lowering effect
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ObjectiveTo inyestigate the effect of miRNA-155 expression on the differentiations and functions of CD4 + T lymphocyte in patients with unstable angina pectoris. MethodsTwenty-one patients with unstable angina pectoris (UAP) were enrolled in this study, and another 18 patients with normal coronary arteries evidenced by angiography were assigned as control group. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of miRNA-155 in CD4 + T lymphocyte of the peripheral blood. And the levels of IFN-γ and IL-4 in serum were determined by using enzyme-linked immunosorbent assay (ELISA). The CD4 + T lymphocyte were isolated from mononuclear cells prepared with Ficoll-Hypaque density-gradients centrifugation from human peripheral blood by magnetic cell sorting system. Then, the CD4 +T cells (2 × 106 cells/mL) were seeded in culture plates with 6 wells.The CD4 + T lymphocytes were divided into 3 groups in experiment: control group, miRNA-155 group, and miRNA-155 inhibitor group. The numbers of Th1 and Th2 cells were measured by flow cytometry analysis (FACS).The protein levels and expressions of IFN-γRα, T-bet, GATA-3 mRNA were measured by using western blotting and qRT-PCR, respectively. The levels of IFN-γ and IL-4 in culture supernatants of CD4 +T lymphocytes were detected by using ELISA. ResultsIn comparison with the control group, there was significant increase in the expression of miRNA-155 and serum level of IFN-γ in the UAP group (P ＜0. 01 ). There was a positive correlation between miRNA-155 and serum IFN-γ ( r =0. 842, P ＜ 0. 0l ).However, in vitro, the number of Th1, the protein level and expression of T-bet mRNA, and supernatant IFN-γ increased, and the protein level and expression of IFN-γRα protein decreased in miRNA-155 group in comparison with the control group (all P ＜0. 01 ). Interestingly, there were no significant differences in the number of Th2 cells, the expressions of GATA-3mRNA and IFN-γRα mRNA, GATA-3 protein and supernatant IL-4 between control group and miRNA-155 group ( all P ＞ 0. 05 ). And the miRNA-155 inhibitor could attenuate the effect of miRNA-155 effectively. ConclusionsThe miRNA-155 can promote differentiations and improve the function of Thl, playing an important role in the pathogenesis of unstable angina pectoris.
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BACKGROUND: The nano-hydroxyapatite/bacterial cellulose (nHAP/BC) nanocomposites has a good prospect of application in bone tissue engineering, and the bone tissue engineered materials and its degradation products Should have excellent compatibility. This study further assessed DAN synthesis cycle using flow cytometry on the basis of evaluating cell compatibility by metabolic 3-(4, 5-dim ethylthiazo 1-2-y 1) -2, 5-Dipheny 1-2H-tetrazolium (MTT) assay. OBJECTIVE: To evaluate the cytocompatibility of a new-pattern nHAP/BC nanocomposites and its residues. METHODS: Effects of nHAP/BC nanocomposites and its residues on morphclogicel changes in osteoblasts were observed using in vitro cell culture method. Effects of nHAP/BC nanocomposites and its residues on osteoblast growth and prclifera'don were evaluated by MTT assay. Cell cycle phase changes were detected using flow cytometry to evaluate matsdal effects on cell proliferation on molecular levels. RESULTS AND CONCLUSION: The nHAP/BC nanocomposites and its residues had neither remarkable effects on cell morphology, nor significant inhibition on osteoblast growth and proliferation. Test of MTT cytotoxicity showed that the average cell proliferation rate was over 80% after treated with the material and its residues, with the cytotoxity grade of 1 (non-toxic). Flow cytometry indicated that the rate of G_0/G_1 was reduced, and the rates of S, G2/M were increased, and the synthesis of DNA was increased, the cellular growth and repair in osteoblasts was accelerated. These indicated that nHAP/BC nanocomposites have good cytocompatibility, and it will be safe and prospected scaffolds in bone tissue engineering.
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Objective To investigate the cause of high cardiovascular lethality in patients with diabetics mellitus. Methods Sections from autopsied coronary arteries and myocardium of dead patients with non-insulin-dependent diabetics mellitus and 12 dead control subjects were used for histomorphometric studies. Results The coronary atherosclerotic lesion in diabetics patients was not different in severity from those in controls. Nor was there difference in number of myofibers or diameters of myocardic fibers and capillaries.But the capillary density and the ratio of capillary number to myocardic fiber number in diabetics group were significeantly reduced compared with control group(P<0.0 l),and the capillary basement membrane in the former was significantly thicker than in the latter(P<0.01).Conclision The decrease in number of capillaries and the thickening of basement membrane enhance myocardiac vulnerability to further ischemia and hypoxia,which may undelie high lethality of myocardiopathy in diabetic patients.
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@#Objective To observe the effect of magnetic stimulation of sacral roots on detrusor overactivity and urge incontinence after spinal cord disease.Methods 15 cases with detrusor overactivity and urge incontinence after spinal cord disease were treated with magnetic stimulation of sacral roots for 10 d.Voiding diary,quality of life scale and urodynamic investigation were applied to evaluate the effect.Results The mean frequency of voiding in 24 h after treatment decreased,urine volume increased,frequency of incontinence decreased and the quality of life score improved.Urge incontinence improved in 85.7% cases.The results of urodynamic investigation showed bladder capacity at first desire to void and maximum cystometric capacity significantly increased after stimulation,while the detrusor pressure at storage decreased.Conclusion Magnetic stimulation of sacral roots can improve urinary frequency and urge incontinence of patients with detrusor overactivity after spinal cord disease by inhibiting detrusor overactivity,increasing cystometric capacity.Magnetic stimulation of sacral roots may be an alternative promising rehabilitation technique.