Optogenetic activation of dorsal hippocampal astrocytic Rac1 blocks the learning of associative memory / 生理学报

Rac1 belongs to the family of Rho GTPases, and plays important roles in the brain function. It affects the cell migration and axon guidance via regulating the cytoskeleton and cellular morphology. However, the effect of its dynamic activation in regulating physiological function remains unclear. Recently, a photoactivatable analogue of Rac1 (PA-Rac1) has been developed, allowing the activation of Rac1 by the specific wavelength of light in living cells. Thus, we constructed recombinant adeno-associated virus (AAV) of PA-Rac1 and its light-insensitive mutant PA-Rac1-C450A under the control of the mouse glial fibrillary acidic protein (mGFAP) promoter to manipulate Rac1 activity in astrocytes by optical stimulation. Primary culture of hippocampal astrocytes was infected with the recombinant AAV-PA-Rac1 or AAV-PA-Rac1-C450A. Real-time fluorescence imaging showed that the cell membrane of the astrocyte expressing PA-Rac1 protruded near the light spot, while the astrocyte expressing PA-Rac1-C450A did not. We injected AAV-PA-Rac1 and AAV-PA-Rac1-C450A into dorsal hippocampus to investigate the role of the activation of Rac1 in regulating the associative learning. With optical stimulation, the PA-Rac1 group, rather than the PA-Rac1-C450A group, showed slower learning curve during the fear conditioning compared with the control group, indicating that activating astrocytic Rac1 blocks the formation of contextual memory. Our data suggest that the activation of Rac1 in dorsal hippocampal astrocyte plays an important role in the associative learning.

A Case Control Study for Risk Factors in Patients of Acute Myocardial Infarction Complicated With Cardiac Rupture / 中国循环杂志

Objective: To analyze clinical characteristics and risk factors in patients with acute myocardial infarction (AMI) complicated with cardiac rupture (CR) and to explore the prevention and treatment strategy in clinical practice. Methods: A case control study was conducted in 2 groups: CR group, the patients with coronary angiography conifrmed AMI with CR,n=44 and Control group, the patients with simultaneous STEAMI and by 1:3 pair-matched ratio,n=132. Clinical information was compared between 2 groups and the relevant risk factors for predicting CR were studied by Logistic regression analysis. Results: Compared with Control group, CR group had the lower ratio of β-receptor blocker application (22.7% vs 81.4%),P<0.05. Univariate regression analysis indicated that lower body mass index, incipient MI, anterior MI, no-reperfusion therapy, delayed reperfusion therapy, lower blood pressure at admission, post-infarction angina, ventricular aneurysm, higher Gensini score, high blood levels of cretinine and BNP, low ejection fraction were the risk factors for CR occurrence in STEAMI patients, allP<0.05. Multivariate regression analysis presented that incipient MI (P<0.049, OR=7.462), post-infarction angina (P<0.000, OR=8.591), ventricular aneurysm (P<0.005, OR=4.617) and higher Gensini score (P<0.001, OR=2.788) were risk factors for CR occurrence in STEAMI patients. Conclusion: Incipient MI, post-infarction angina, ventricular aneurysm and higher Gensini score are the risk factors for CR occurrence in STEAMI patients.

Efficacy of levosimendan on cardiac function of patients with decompensated heart failure / 中国综合临床

Objective To evaluate the improvement effect of levosimendan by vein injection on short term cardiac function of patients with decompensated heart failure.Methods One hundred and sixty patients admitted due to heart failure were randomly divided into levosimendan group and control group (80 subjects for each group).Patients in control group were given a regular therapy including diuretics,vasodilators (including the recombinant human brain natriuretic peptide),angiotensin converting enzyme inhibitor(ACEI) or angiotensin Ⅱ receptorantagonists(ARB),β blockers,spironolactone and stain.Patients in levosimendan were administered levosimendan for 24 hours plus regular therapy.The improvements of dyspnoea in 9 days and cardiac function classification in 30 days after therapy were assessed.Mortality of 1 month and 3 month in two group were calculated and compared during follow-up.Results The dyspnoea improvement rate was superior than that of control group during 9 days (OR =1.956,95％ CI:1.156-3.310,P =0.013).The improvements in the levosimendan group were better than in the control group at 1 st day (OR =2.261,95 ％ CI:1.280-3.999,P =0.005),at 3rd (OR =2.002,95 ％ CI:1.111-3.607,P =0.021) and 5th day (OR =1.846,95 ％ CI:1.009 -3.377,P =0.047).However,there was no significant difference in term of improving dyspnoea between the levosimendan group and the control group at 9th day (P =0.126).Similarly,the improvement of cardiac function classification in the levosimendan group was superior than the control group during 30 days (OR =1.933,95％ CI:1.229-3.040,P =0.004).Although no significant difference was seen regarding of improving cardiac function classification between the two groups at 30th day after treatment (P =0.115),the improvements in the levosimendan group were better than in the control group at 3rd (OR =1.986,95％ CI:1.195-3.300,P =0.008),5th (OR =2.268,95 ％ CI:1.329-3.873,P =0.003),9th (OR =2.627,95 ％ CI:1.419-4.860,P =0.002) and 14th day(OR =2.212,95％ CI:1.189-4.112,P =0.012).Moreover,there was a nonsignificant reduction in terms of mortality in levosimendan group during 1-month and 3-month follow-up compared with control group (P ＞ 0.05).Condusion Levosimendan can effectively improve the short-term cardiac function in patients with decompensated heart failure.

The relationship of regular exercise and coronary collateral of patients with acute coronary syndrome / 中国综合临床

Objective To investigate the relationship between regular exercise habit and coronary collaterals of patients with acute coronary syndrome (ACS).Methods TWo hundred and thirty-night patients diagnosed ACS and operated coronary angiography (CAG) showing severe coronary stenosis were enrolled hospitalized from May 2012 to October 2012.They were divided into regular exercise group (n =102) and irregular exercise group(n =137) according to the exercise frequency.The information of the general data,the information of CAG and other relevant index were collected.The coronary artery score was recorded according to the Censini and the coronary collateral class was made according to the Rentrop.Other characters in clinical and laboratory were recorded.Multi-factor regression analysis was used to analysis the influence factors of coronary collateral.Results The proportion of coronary collaterals (41.2％ (42/102)) in the regular exercise group was higher than that in the irregular exercise group (24.1％ (33/137)),and the difference was statistically significant(x2 =7.929,P =0.005).Lg(Gensini score) was (1.89 ± 0.18) the and (1.94 ± 0.19) in the regular exercise group,The left ventricular ejection fraction was 57.0％ (52.0％,60.0％) in the regular exercise group and 50.0％ (45.0％,57.0％) in the irregular exercise group,and the difference was statistically significant (Z =-5.152,P =0.000).Multi-factor regression analysis showed that regular exercise (OR =3.423,95％ CI:1.790-4.578),diabetes mellitus (OR =0.451,95％ CI:0.212-0.962),B-type natriuretic peptide (OR =2.412,95 ％ CI:1.271-4.578),non-ST-segment elevation ACS (OR =2.383,95％ CI:1.185-4.791),chest pain history (OR =2.207,95％ CI:1.175-4.145),Gensini score (OR =1.538,95％ CI:1.141-2.073) were independent influence factors of coronary collateral(P ＜ 0.05).After adjusting other factors,the patients with regular exercise had better coronary collaterals than that with irregular exercise (OR=3.423,95％CI:1.790-6.548,P ＜0.001).Conclusion The regular exercise can promote coronary collateral emergence for the patients with ACS.

Efficacy of levosimendan vs.milrinone in decompensated heart failure patients / 中华急诊医学杂志

Objective To evaluate the short-term clinical efficacy and safety of administration of levosimendan or milrinone added to conventional therapy in patients with decompensated heart failure.Methods A total of 180 patients admitted due to heart failure [NYHA (New York Heart Association) class Ⅲ or Ⅳ] were randomly (random number) divided into control group,milrinone group and levosimendan group (n =60,each group).A continuous infusion of milrinone added to conventional therapy was administered for 72 hours in milrinone group,while administration of levosimendan for 24 hours in levosimendan group.The changes in left ventricular ejection fraction (LVEF),left ventricle end-diastolic diameter (LVDD) and B-type natriuretic peptide (BNP) plasma level were compared between before and after treatment,respectively,and comparisons of improvement in cardiac function (NYHA class) and hospital mortality were carried out among three groups.Patients were further followed up at 3 months after treatment.Results The LVEF in levosimendan group after treatment had significantly more increased than that in control group [(32.0±6.3)％ vs.(30.6 ±5.5)％,P =0.007].Compared BNP before treatment,the sums of BNP deducted were 444.0 (-74.0,1068.0) pg/mL,469.0 (141.5,1151.5) pg/mL and 936.5 (437.8,1566.8) pg/mL in control group,milrinone group and levosimendan group,respectively after treatment (all P ＜ 0.01).Moreover,the deduction in BNP was more dramatic in levosimendan group compared with control or milrinone group (t =3.256 or 2.665,P =0.004 or 0.026).After treatment for 5 days,the probability at least of achieving more effectively better improvement in NYHA class (cardiac function) in levosimendan group was 2.036 times that of control group (95％ CI:1.030-4.028,P =0.041).The incidence of combined end point events (death or readmission) in levosimendan group was significantly lower than that in milrinone group (50％ vs.70％,HR =0.573,95％ CI:0.358-0.917,P=0.020),while in hospital mortality,readmission or 3-month mortality incidence was similar among 3 groups (P ＞ 0.05).Conclusions The short-term clinical efficacy of levosimendan is superior to that of milrinone or conventional therapy in patients with decompensated heart failure.

Short-term clinical efficacy of levosimendan on treating decompensated cardiac insufficiency / 中国综合临床

Objective To investigate the short-term clinical efficacy of levosimendan on treating patients with decompensated cardiac insufficiency.Methods One hundred and twenty patients with heart failure (NYHA Ⅲ-Ⅳ or Killip Ⅲ) were randomly divided into levosimendan group(n =60) and control group(n =60).The patients in levosimendan group were given intravenous levosimendan for 24 hours beside conventional heart failure medications.The patients in control group were given the conventional heart failure medications.The left ventricular ejection fraction (LVEF) was recorded and B-type natriuretic peptide (BNP) were measured before and after treatment.NYHA grade and mortality also were recorded.All patients were followed up for 3 months.Results The LVEF in the levosimendan group after the treatment was (35.6 ± 13.3)％,significantly higher than that in the control group ((31.4 ± 6.7) ％,F =8.952,P =0.002).The BNP in two groups after treatment were lower compared with before treatment(P ＜0.05).And it was more remarkable after treatment in levosimendan group compared with control group (441.0 (212.5,1050.0) ng/L vs.870.0 (435.0,1267.0) ng/L,P =0.014).The change of NYHA grade in levosimendan group was better than that in control group after 5 d.The recovery rate and ineffective or deterioration rate in levosimendan group were 45.0％ (27/60),26.7％ (16/30) and 43.3％ (26/60) respectively,higher than that of control group (28.3％ (17/60),20.0％ (12/60),36.7％ (22/60)) (OR =2.280,95％ CI 1.163-4.468,P =0.016).There was no significant difference in term of mortality between in hospital and 3 months follow-up in the levosimendan and the control group (20％ (12/60) vs.25％ (15/60),28.3％ (17/30) vs.41.7％ (25/60),x2 =1.543,P =0.214 and x2 =2.590,P =0.108).There was a decreasing trend regarding of readmission rate during 3 months in levosimendan group compared with that of the control group (21.7％ (13/60) vs.33.3％ (20/60),x2 =3.591,P =0.058),but mortality or readmission rate was lower than that in the control group (46.7 ％ (28/60)vs.66.7％ (40/60),x2 =4.835,P =0.028).Conclusion The short-term clinical efficacy of levosimendan on treating patients with decompensated cardiac insufficiency is remarkable better than the traditional treatment.

Clinical observation of recombinant human brain natriurefic peptide in acute anterior myocardial infarction complicated with heart failure / 中国综合临床

Objective To evaluate the efficacy of intravenous recombinant human brain natriuretic peptide in acute anterior myocardial infarction complicated with heart failure.Methods Two hundred patients suffered from acute anterior myocardial infarction complicated with heart failure were randomly divided into two groups:rhBNP group ( n =100) and control group ( n =100 ).All patients were given conventional treatment,patients in rhBNP group were given rhBNP on the basis of conventional therapy.The clinical effectiveness including the improvement of cardiac function,cardiac ultrasound data,the incidence of hospital adverse cardiac events,and six month follow-up were compared between the two groups.Results The degree of decompensation and Killip class in rhBNP group were better than those of control group after treatment ( improved dyspnea:significantly improved:36 vs 27 ; improved:49 vs 46; no improvement:11 vs 20 ; deterioration:4 vs 7 ; Ridit value:0.4618 vs 0.5382,P =0.043) ( Killip class:significantly improved:26 vs 20; improved:56 vs 45; no improvement:14 vs 25 ; deterioration:4 vs 10; Ridit value:0.4553 vs 0.5447,P =0.017 ).After treatment for one week,The LVEF improvement in rhBNP group was more remarkable than that of control group ( [ 53.0 ± 5.2 ] ％vs.[ 50.0 ±:6.2 ] ％,P =0.014).The occurrence rate of angina ( 13.0％ vs.27.0％,P =0.013 ),heart failure ( 18.0％ vs.32.0％,P =0.022) and major adverse cardiac events(MACE) ( 17.0％ vs.30.0％,P =0.030) inrhBNP group was lower than that in control group.During 6 months follow-up period,event-free survival in rhBNP group was higher than that in control group ( 69.0％ vs.55.0％,P =0.041 ).Conclusion Transvenous injection of rhBNP combined with other routine treatment can improve cardiac function in patients with myocardial infarction in acute anterior myocardial infarction.It can also decrease adverse cardiac events during hospitalization and increase event-free survival in 6 months follow-up period.

Discussion on transmission mechanism of wild rodent plague to human in the northwestern area of Yunnan province / 中国地方病学杂志

Objective To explore the relationship between wild rodent plague and human in wild rodent plague foci of the northwestern area in Yunnan to probe the possible transmission mechanism of wild rodent plague to human. Methods Data of component ratio of rodents and fleas was collected in different areas from 1985 - 1995. Activities and habits of residents regarding the way they keep cats and dogs and parasitic fleas and free fleas indoor were investigated, the dog serum was collected for detecting F1 antibody. Results Eothenomys miletus were main rodents in farmland and shrub, accounting for 48.00% (4753/9902) and 54.50% (4282/7857), Apodemus chevrieri were main rodents in garden, being 50.47% (1332/2639). The component ratio of Neopsylla specialis specialis was 13.31%(229/1720), 12.31%(1678/13 739) and 10.87%(957/8802) respectively in garden, farmland and shrub, higher than in indoor. The component ratio of Frantcpsylla spodix was 39.88% (686/1720), the highest in garden. Thirty-two per cent (32/100) of residents kept cats,in which 63% (20/32) with cat fleas, 68% (68/100) of villages kept dogs, in which 76%(52/68) with fleas. Eighteen parasitic fleas were caught from 43 dogs with a flea index of 0.119 and a rate for fleas of 11.63%, 7 pulex were collected from 17 indoor. Forty-three blood serum samples were obtained from dogs, among which 3 were positive blood serum. Conclusions Residents touch affected animals or media in different situations. The possibility of transmission for wild rodent plague to human exists in loci in a chain of wild rodent plague → fleas or predation → homebred animal plague (cats or dogs) →touching or respiratory → human.

Cause of micromotion in distal femoral prosthesis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate possible causes of micromotion in distal femoral prosthesis.</p><p><b>METHODS</b>Based on the assumption that the femur and prosthesis were considered as concentric cylinders with completely bonded interface, a theoretical model simulating the interfacial stress transfer was established. The distributions of the interfacial shear and radial stresses with the changing of z were obtained through mathematics and mechanics deducing.</p><p><b>RESULTS</b>The maximum interfacial shear stress occurred at the position of z=0, namely, the cross section of the femur neck. The interfacial shear stress sharply decreased with the increasing of z and came to nearly zero at the range of z> 0.1 m. While the interfacial radial stress increased with the increasing of z,at the range of z >0.05 m it was constant and reached the maximum.</p><p><b>CONCLUSION</b>The micromotion in distal prosthesis is caused by the interfacial radial stress.</p>

Finite element analysis of impact loads on the femur / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the stress distribution and fracture mechanism of proximal femur under impact loads.</p><p><b>METHODS</b>The image data of one male's femur were collected by the Lightspeed multi-lay spiral computed tomography. A 3D finite element model of the femur was established by employing the finite element software ANSYS, which mainly concentrated on the effects of the directions of the impact loads arising from intense movements and the parenchyma on the hip joint as well as those of the femur material properties on the distribution of the Mises equivalent stress in the femur after impact.</p><p><b>RESULTS</b>The numerical results about the effects of the angle sigma of the impact loads to the anterior direction and the angle gamma of the impact loads to the femur shaft on the bone fracture were given. The angle sigma had larger effect on the stress distribution than the angle gamma, which mainly represented the fracture of the upper femur including the femoral neck fracture when the posterolateral femur was impacted. This result was consistent with the clinical one. The parenchyma on the hip joint has relatively large relaxation effect on the impact loads.</p><p><b>CONCLUSIONS</b>A 3D finite element analysis model of the femoral hip joint under dynamic loads is successfully established by using the impact dynamic theory.</p>