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OBJECTIVE To s tudy the impr ovement effects of tilianin on the atherosclerosis (AS)model mice and its potential mechanism. METHODS Eight C 57BL/6J mice were taken as the normal group. Forty ApoE-/- mice were randomly divided into model group ,tilianin low-dose ,medium-dose and high-dose groups [ 2.1,3.5,7.0 mg/(kg·d)] and simvastatin group [positive control drug ,3.5 mg/(kg·d)],with 8 mice in each group. Normal group was given normal diet ,and other groups were given high-lipid diet to induce AS model. At the same time ,normal group and model group were given normal saline intragastrically , administration groups were given relevant drug intragastrically ,once a day ,for 12 consecutive weeks. The levels of TC ,TG, LDL-C,HDL-C,Ox-LDL,IL-1β,IL-6,MCP-1 and TNF-α in plasma were determined. The pathomorphological changes of the aorta in mice were observed. The positive rate of ICAM- 1,VCAM-1 and PCNA in the aorta were determined. mRNA expressions of MMP- 2,MMP-9,TGF-β1,Smad2 and Smad 3 as well as protein expressions of TGF-β1,Smad2/3 and p-Smad 2/3 were also determined in aorta of mice. RESULTS Compared with normal group ,the plasma levels of TC ,TG,LDL-C,Ox-LDL,IL-1β, IL-6,MCP-1 and TNF-α in model group were increased significantly(P<0.01),while HDL-C level was significantly reduced (P<0.01). Lipid plaques were formed in the aorta ,and the plaque area was large and caused severe stenosis of the lumen. mRNA expressions of MMP- 2,MMP-9,TGF-β1,Smad2 and Smad 3 as well as positive rate of ICAM- 1,VCAM-1,PCNA and protein expression TGF-β1,Smad2/3,and p-Smad 2/3 in the aorta were significantly increased (P<0.01). Compared with model group , most of above indexes of medication groups were improved significantly (P<0.05 or P<0.01). CONCLUSIONS Tilianin can inhibit the activation of TGF-β1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells ,reduce , inflammation and regulate lipid metabolism to inhibit the No.81960766) formation of AS.
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OBJECTIVE:To s tudy the effects of Dracocephalum moldavica total flavonoids (TFDM)on AMPK/SIRT 1/PGC-1α signaling pathway ,and to explore the mechanism of its protective effect on myocardial ischemia reperfusion injury (MIRI)rats. METHODS:Totally 50 healthy male SD rats were randomly divided into sham operation group ,model group ,TFDM group [ 60 mg/(kg·d),by extract] ,Compound C+TFDM group [ig administration of 60 mg/(kg·d)TFDM+intravenous injection of 250 μg/kg Compound C(AMPK inhibitor )via tail vein 15 min before reperfusion] ,EX-527+TFDM group [ig administration of 60 mg/ (kg·d)TFDM+ip injection of 5 mg/kg EX- 527(SIRT1 inhibitor)20 min before reperfusion] ,with 10 rats in each group. They were given relevant medicine intragastrically ,once a day ,for consecutive 7 days. After last ig administration ,sham operation group underwent sham operation ,other 4 groups were established MIRI model by ligating left anterior descending coronary artery , ischemia for 30 min and reperfusion for 2 h. After reperfusion ,the myocardial histopathological changes were observed by HE staining;RP-HPLC method was used to determine the contents of ATP ,ADP,AMP and NAD + in cardiac tissue. mRNA expressions of AMPK ,SIRT1 and PGC- 1α were detected by quantitative real-time PCR assay. Western blotting assay was the expressions of SIRT 1 and PGC- 1α protein in myocardium. RESULTS: Compared with sham operation group , model group showed myocardial fib ers arranged disorder and horizontal stripes disappearance ,cell swelling burst and necrosis ,and nuclei deformation displacement ;the contents of ATP and NAD+,mRNA expression of AMPK ,SIRT1 and PGC- 1α,protein expression of SIRT 1 and PGC- 1α in cardiac tissue were decreased significantly (P<0.05 or P<0.01);the contents of ADP and AMP ,the phosphorylation level of AMPK protein were increased significantly (P<0.01). Compared with model group ,myocardial pathological morphology were improved significantly in TFDM group ;the contents of ATP and NAD + in cardiac tissue ,mRNA expression of AMPK ,SIRT1 and PGC- 1α,the phosphorylation level of AMPK protein ,the protein expression of SIRT 1 and PGC- 1α were increased significantly(P<0.05 or P< 0.01),while the contents of ADP and AMP were decreased significantly (P<0.01). Compared with TFDM group ,improvement effects of Compound C + TFDM group and EX- 527 + TFDM group on above indexes were reversed (P<0.05 or P<0.01). CONCLUSIONS:TFDM may play a protective role on myocardium by activating AMPK/SIRT 1/PGC-1α signaling pathway and regulating energy metabolism.
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Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.
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Objective To investigate the expression of IL-10 and IL-6 in tissue and plasma of subtypes lymphoma and its significance. Methods Immunohistochemical technique and enzyme-linked immunosorbent assay (ELISA) were used to assess the expression of IL-10 and IL-6 in 97 cases paraffin tissue and plasma samples from different subtypes of lymphoma.Results Expression of IL-10 and IL-6 was positive in all lymphoma tissue samples, but there is no significant difference among different subtypes lymphoma (x2 =0.815, x2 =0.542, P > 0.05). Tumor samples were found positive IL-10 and IL-6 expression in macrophages and vascular endothelial cells by immunohistochemistry respectively. Expression of IL-10 and IL-6 in plasma of lymphoma were higher than that in control respectively [(232.57±191.59) pg/ml vs (59.12±68.35) pg/ml,(80.70±89.68) pg/ml vs (45.68±33.66) pg/ml],with significant difference (t =6.968,t =2.896,P <0.05).IL-10 and IL-6 plasma levels increased with enhanced expression in lymphoma (x2 =0.815,x2 =0.542,P < 0.05).Which was found to be correlated with each other (rs =0.394,P < 0.05). Conclusion The expression of IL-10 and IL-6 had been found at various degrees in tissues and plasma of lymphoma.IL-10 and IL-6 in plasma of lymphoma were higher than that in controls. These results showed that IL-10 and IL-6 may cooperate in vivo with lymphoma cell proliferation and infiltrate. IL-6 and IL-10 maybe served as useful indicators for diagnosis of lymphoma.
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Objective To investigate the factors implicated in the outcomes of patients with invasive pulmonary aspergillosis (IPA).Methods During a 5-year period,65 patients with IPA met the criteria set by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG)in 2008 were retrospectively evaluated. The initial CT findings of eligible patients were reviewed by two senior radiologists who specialized in chest radiology.Patients were divided into the survivor (n =43 ) and non-survivor (n =22) groups according to their survival as long as 3 months after the diagnosis of IPA was made.An initial univariate analysis was used to screen variables that were related to prognosis,followed by a multivariate logistic regression analysis to examine these variables. Results Of the 65 IPA patients analyzed,23 (35%) had a proven diagnosis and 42 (65%) were probable ones.The univariate analysis showed that the rates of extra-pulmonary infection,uncontrolled underlying diseases and invasive mechanical ventilation were significantly different between the 3-month survival group and the non-survival group ( P <0.05,respectively),whereas chest CT findings,including air-space consolidation/massive consolidation,macronodules,infarct-like macronodules,halo signs, ground-glass opacities,small nodules,hypodense signs,cavities,crescent signs,small-airway findings,bronchial wall thickening/bronchiectasis,pleural effusion and hydro-pericardium, were not significantly different between the two groups (P > O.05,respectively).Logistic regression analysis revealed that an uncontrolled underlying disease was the only independent predictor of 3-month mortality in patients with IPA (P =0.001,OR:O.024,95 % CI:O.003 ~0.223,B =- 3.714,SE =1.129,Wald =10.821 ). Conclusions An uncontrolled co-morbidity was the only independent predictor of mortality within 3 months in patients with IPA.The initial CT findings did not confer any informatioin of implication in predicting the outcomes of IPA patients.
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Background The present study investigated the prognostic value of medical comorbidities at admission for 30-day in-hospital mortality in patients with acute myocardial infarction (AMI). Methods A total of 5161 patients with AMI were admitted in Chinese PLA General Hospital between January 1,1993 and December 31,2007. Medical comorbidities including hypertension, diabetes mellitus, previous myocardial infarction, valvular heart disease, chronic obstructive pulmonary disease (COPD), renal insufficiency, previous stroke, atrial fibrillation and anemia, were identified at admission. The patients were divided into 4 groups based on the number of medical comorbidities at admission (0, 1, 2, and ≥ 3). Cox regression analysis was used to calculate relative risk (RR) and 95% confidence intervals (CI), with adjustment for age, sex, heart failure and percutaneous coronary intervention (PCI). Results The mean age of the studied population was 63.9 ± 13.6 years, and 80.1% of the patients were male. In 74.6% of the patients at least one comorbidity were identified. Hypertension (50.7%), diabetes mellitus (24.0%) and previous myocardial infarction (12%) were the leading common comorbidities at admission. The 30-day in-hospital mortality in patients with 0, 1, 2, and ≥ 3 comorbidities at admission (7.2%) was 4.9%, 7.2%, 11.1%, and 20.3%, respectively. The presence of 2 or more comorbidities was associated with higher 30-day in-hospital mortality compared with patients without comorbidity (RR: 1.41, 95% CI: 1.13-1.77, P = 0.003, and RR: 1.95, 95% CI: 1.59-2.39, P = 0.000, respectively).Conclusions Medical comorbidities were frequently found in patients with AMI. AMI patients with more comorbidities had a higher 30-day in-hospital mortality might be predictive of early poor outcome in patients with AMI.
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Objective To explore the clinical outcome of HLA haploidentical vs HLA-matcbed peripheral blood hematopoietic stem cell transplantation (PBSCT) without in vitro T-cell depletion for malignant hematological diseases. Methods 111 patients with malignant hematological diseases underwent PBSCT without in vitro T-cell depletion between May 2004 and February 2009, including 51 patients with HLA-haploidentical and 60 patients with HLA-matched. All patients have received myeloablative conditioning regimen. A two-agent based graft-versus-host disease (GVHD) prophylaxis was used as cyclosporine A and a short course of methotrexate. Mycophenolate mofetile was added for the patients with one locus mismatch. Mycophenolate mofetile, antithymocyte globulin and CD25 monoclonal antibody were added for the patients with 2-3 loci mismatch. The grafts were granulocyte colony-stimulating factor-mobilized peripheral blood stem cells without in vitro T-cell depletion. Results 111 patients achieved sustained and full donor-type engraftment. The median time to reach an absolute neutrophil count above 0.5×10~9/L was 14 days and that to a platelet count exceeding 20×10~9/L was 15 days in 51 HLA-haploidentical patients, and that was 12 days and 13 days in 60 HLA-matched patients, respectively. In 51 HLA-haploidentical patients, 25 patients developed aGVHD, including 20 cases of grade Ⅰ aGVHD, and 5 cases of grade Ⅱ. Thirty-three patients developed cGVHD with limited in 30 and extensive in 3. The 4-year cumulative incidence of cGVHD was 70.4 %. The 3-year probabilities of leukemia-free survival (LFS) were 74.5% (77.3 % for standard risk patients and 68.2 % for high risk patients respectively). Seven patients had recurrence. In 60 HLA-matched patients, 14 patients developed aGVHD, including 10 cases of grade Ⅰ, 2 cases of grade Ⅱ and 2 cases of grade Ⅲ. Thirty-seven patients developed cGVHD with limited in 32 and extensive in 5. The 4-year cumulative incidence of cGVHD was 58.1%. The 3-year probabilities of LFS were 72.1% (77.6 % for standard risk patients and 52.7 % for high risk patients respectively). Ten patients had recurrence. The incidence of aGVHD in HLA-haploidentical cohort was significantly higher than in HLA-matched cohort (P<0.05). There was no significant difference in incidence of cGVHD, incidence of relapse and LFS between HLA-haploidentical and HLA-matched cohorts (P>0.05). Conclusion Haploidentical PBSCT is feasible and safe for malignant hematological diseases to use myeloablative conditioning regimen in combination with intensive immunosuppressants without in vitro T cell depletion.
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Objective To investigate the relationship of blood pressure circadian rhythm with myocardial hypertrophy and the changes of autonomic nerve function in patients with essential hypertension (EH). Methods Eighty-two female patients with essential hypertension (EH) underwent 24-hours ambulatory blood pressure monitorings (ABPM), dynamic electrocardiogram (Holter) and echocardiography examination. Patients were classified into non-dipping group (n=40) and dipping group (n=42) according to the result of ABPM. Left ventricular mass index (LVMI), heart rate variability (HRV) in time domain (including SDNN, SDANN, rMSSD, PNN50) and heart rate turbulence (HRT) parameters (including turbulence onset [TO] and turbulence slope [TS]) were measured. Results Compared with those in dipping group, patients in non-dipping group have higher incidence of LVH (19.0% vs 52.5%, P<0.01), greater mean LVMI (112.39±12.79 g/m2 vs 121.98±13.35 g/m2, P<0.01), decreased PNN50 and rMSSD. TS value was decreased while TO was increased in non-dipping group compared with those in dipping group (both P <0.01); patients with LVH showed decreased TS and increased TO, compared with those without LVH. Conclusion In female patients with EH, non-dipping blood pressure circadian is associated with higher incidence of LVH. The HRV and HRT were more remarkably blunted in non-dipping patients, as well as those with LVH.
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Objective We aimed to investigate whether magnetic stent has preventive effect on in-stent restenosis by observing expressions of matrix metalioproteinase (MMP)2,MMP9,tissue inhibitor of matrix metalloproteinase (TIMP)1 and TIMP2 after balloon angioplasty,bare and magnetic stent implantation in rabbits.Methods Rabbits underwent balloon angioplasty,bare and magnetic stent implantation in the left iliac arteries.The changes of MMPs and TIMPs were examined at various time points in the injured arteries using the methods of zymography,Western blot analysis,reverse transcription-polymerase chain reaction (RT-PCR) and morphometric analysis.Results Balloon angioplasty group (BA) and magnetic stent group (MS) showed lower intrinsic gelatinolytic activity and higher expression of TIMPs with less intimae hyperplasia;Whereas bare stent (BS) group exhibited higher intrinsic gelatinolytic activity and lower expression of TIMPs with significant intimae hyperplasia.Conclusion Magnetic stent probably has preventive effect on in-stent restenosis by changing intrinsic matrix metalloproteinases activity and expression of TIMPs.
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Overt gastrointestinal bleeding (GIB) is one of the noncardiac complications in patients with acute myocardial infarction (AMI).Identification of patients at increased risk of overt GIB could aid in targeting more aggressive treatment,and lead to improved outcomes.The aim of this study is to determine the frequency,risk factors,and prognostic significance of overt GIB in patients with AMI.Methods A retrospective review of the medical records of 1443 patients admitted to the Chinese PLA General Hospital with AMI was conducted.Charts were reviewed for clinical characteristics,possible precipitating factors and complications.Patients were categorized as having or not having overt GIB(GIB associated with hemodynamic changes or the need for transfusions).Results Twenty nine (2.0%) patients developed overt GIB within 30 days after AMI.Patients with overt GIB had higher 30-day mortality rate than those without (44.8% vs.9.9%,P < 0.001).Multivariate logistic regression analysis showed major determinants of in-hospital overt GIB secondary to AMI were gender of female (odds ratio 2.41,95% confidence interval [CI] 1.08 to 5.37),age=75 years (odds ratio 1.58,95% CI 1.13 to 2.20),prior history of AMI (odds ratio 2.28,95% CI 1.17 to 4.88),pneumonia (odds ratio 3.47,95% CI 1.50 to 8.03) and anemia at admission (odds ratio 2.37,95% CI 1.04 to 5.37).Conclusions In patients with AMI,overt GIB is associated with higher in-hospital mortality,and female sex,older age,prior AMI,pneumonia and anemia at admission are predictors of overt GIB during hospitalization.(J Geriatr Cardiol 2008;5:195-198)
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Objective To investigate the preventive effect of magnetic stent on coronary restenosis after percutaneous arterial stenting.Methods Twenty rabbits were divided randomly into 2 groups.Bare stent(BS group,n=10)or magnetic stent(MS group,n=10)wasimplanted in the left iliac artery of the rabbits of the 2 groups,respectively.Aspirin (25mg,qd )was administered orally to the rabbitsof both groups from 3 days before stenting until the rabbits were executed.Unfractionated heparin (2500u,qd) was delivered subcuta-neously after stenting for 7days.Five rabbits of each group were randomly selected to be executed at 7 or 30 days.Stmctural changesin the iniured arteries were studied by optical microscopey,transmissive electronic microscopey and immunohistochemistry.ResultsAt 7 days.more myofibroblasts were found migrating from adventitia to tunica media and intima in BS group than in MS group.insidethe media and intima,large amount of smooth muscle cells of synthetic type were observed.At 30 days after stenting,in magnetic group,most uascular smooth musele cells(SMCs)under the intima had transformed to contractile type and only little extracellular matrix(ECM)was observed around the SMCs;whereas,in BS group,the SMCs remained to be synthetic type and large amount of ECM wasobserved around the SMCs.which was composed mainly of proteoglycans and glycoproteins. Conclusions Magnetic stent caninhibit proliferation and migration of SMCs and reducing the production of ECM.and therefore,may prevent restenosis after coronarystenting.
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<p><b>OBJECTIVE</b>To discuss the mechanism of cerebral vessel spasm caused by concussion and the effect of Nimodipine on concussion.</p><p><b>METHODS</b>A total of 224 patients who were treated from March 1995 to October 1999 were divided into two groups randomly, ie, Nimodipine group (113 cases) and control group (111 cases). Middle cerebral artery (MCA), basilar artery (BA) and the average peak forward velocity of cerebral blood flow were observed by color three-dimensional transcranial Doppler (3D-TCD) within 24 hours after admission and at the end of 3-6 days of treatment. Cerebral blood flow changes, characteristics and treatment effect were analyzed and determined by clinical main symptom disappearance rate.</p><p><b>RESULTS</b>In concussion, cerebral blood flow was divided into 3 phases: cerebral blood flow low infusion dilation phase, cerebral blood vessel spasm phase and cerebral blood flow recovery phase. In the Nimodipine group, clinical main symptom disappearance rate was higher than that in the control group in the cerebral spasm and recovery phases with a significant difference (P < 0.01).</p><p><b>CONCLUSIONS</b>Cerebral vessel spasm, hypoxia and ischemia lesion are the main pathological changes. Whether cerebral dysfunction is reversible or not is mainly determined by spasm time of cerebral blood vessel. Nimodipine has a good effect on releasing spasm and diminishing the cerebral blood flow velocity. It not only improves curative effect on concussion, but also reduces and prevents concussion sequelae. Hence, concussion patients who have cerebral spasm confirmed by 3D-TCD should be given Nimodipine routinely and early.</p>
الموضوعات
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Blood Flow Velocity , Brain Concussion , Diagnostic Imaging , Cerebral Arteries , Diagnostic Imaging , Cerebrovascular Circulation , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Follow-Up Studies , Infusions, Intravenous , Injury Severity Score , Mannitol , Nimodipine , Reference Values , Treatment Outcome , Ultrasonography, Doppler, Transcranial , Vasospasm, Intracranial , Drug Therapyالملخص
Objective In order to offer a noninvasive and objective examination method for assessing the clinical diagnosis and eurative criterion of concussion patients, the patients color three - dimensional transcranial doppler( 3D - TCD) characteristic at deferent phases, parameter and clincal manifestation were studied Method Parameter of Median Cerebral Artery(MCA), Base Artery(BA), the average peak forwand velocity of cerebral blood flow, train figure were tested by 3D - TCD within 24 hours, 3 - 6 days and at the end of treatment, respectively. The results were compared with clinical diagnoses and curative criterion. Result Among 135 patients who had clinically diagnosed concussion, agreeable diagnoses 101 cases, basically agreeable diagnooses 12 cases, disagreeable diagnosis 22 cases(16. 2%) .At the end of treatment, according to clinical determination 96 cases(71.1%) were cured, 39 cases(28.9%) were improved. Wave train character, figure and diagnoses prameter of cerebral spasm caused by concussion were suggested Conclusion To be one of the diagnostic bases and curative criterion, 3D- TC D technology is performable. Meanwhile, it is a new testing objective technique for assessing curative and determining prognosis.