Study on improvement effects and mechanism of imperatorin on cachexia model mice / 中国药房

OBJECTIVE To investigate the improvement effects and mechanism of imperatorin on cachexia model mice. METHODS Fifteen male C57BL/6J mice were randomly divided into blank control group， model group and imperatorin group， with 5 mice in each group. Except for blank control group， the remaining mice were inoculated with LLC cell suspension subcutaneously on the dorsal surface， and the drug was administered by gavage daily from the 7th day of inoculation. The imperatorin group was gavaged with imperatorin suspension （0.5% sodium carboxymethylcellulose solution as solvent） at 60 mg/kg； blank control group and model group were given an equal volume of 0.5% sodium carboxymethylcellulose solution， for 13 d of continuous administration. During the administration period， food intake and body mass of mice were recorded daily and regularly， tumor long and short diameters were measured every two days， and tumor volume was calculated. The skeletal muscle mass and tumor mass of each group were weighed and the tumor-free body weight was calculated； the pathological changes of skeletal muscle were observed and the cross-sectional area of skeletal muscle fibers was calculated； the phosphorylation levels of signal transduction and activator of transcription 3 （STAT3） （measured as p-STAT3/STAT3 ratio）， muscle atrophy box F gene （MAFbx）， myostatin （Myog）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase3 protein and mRNA expression were all detected. RESULTS Compared with blank control group， body mass and skeletal muscle mass of model group were decreased significantly （P＜0.05）， and reduced food intake， loose arrangement of skeletal muscle， large cell space were observed； the cross-sectional area of skeletal muscle fiber was significantly reduced， while p-STAT3/STAT3 ratio， protein and mRNA expressions of MAFbx， Bax and Caspase3 were somo_amour@163.com increased significantly （P＜0.05）. The protein and mRNA expressions of Myog and Bcl-2 were significantly reduced （P＜ 0.05）. Compared with model group， body weight， tumor-free weight and skeletal muscle weight were increased significantly in imperatorin group （P＜0.05）； food intake increased， while the expressions of tumor weight and volume were decreased significantly （P＜0.05）； the expressions of above proteins and genes were improved significantly （P＜0.05）. CONCLUSIONS Imperatorin can improve the tumor cachexia state， the mechanism of which may be related to the regulation of ubiquitin-proteasome pathway and anti-apoptosis.

Effects of emergency medical service on prognosis of ischemic stroke patients treated with intravenous thrombolysis / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis.@*METHODS@#Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month.@*RESULTS@#Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all 0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (=0.856, 95%:0.664-1.103, >0.05).@*CONCLUSIONS@#EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.

Advanced treatment time improves outcomes of patients with ischemic stroke undergoing reperfusion therapy / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy.@*METHODS@#The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively.@*RESULTS@#Binary logistic regression showed that DNT (=0.994, 95%:0.991-0.997, <0.01) or DRT (=0.989, 95%:0.983-0.995, <0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis.@*CONCLUSIONS@#Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.

Association of atrial fibrillation with hemorrhagic transformation after intravenous thrombolysis in patients with ischemic stroke / 浙江大学学报·医学版

OBJECTIVE@#To investigate the association of atrial fibrillation (AF) with hemorrhagic transformation (HT) in patients with ischemic stroke treated by intravenous thrombolysis.@*METHODS@#Clinical data of 3272 patients treated by intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and December 2018 were retrospectively reviewed. Intracranial HT was defined as intracranial hemorrhage suggested by imaging examination 24 hours after intravenous thrombolysis. Patients were dichotomized into HT group (=533) and non-HT group (=2739). The association of AF and HT was analyzed by univariate analysis and binary logistic regression.@*RESULTS@#Compared with the non-HT group, the HT group were older, had longer onset to needle time (ONT), higher baseline National Institute of Health Stroke Scale (NIHSS) score, higher baseline glucose level, and higher AF rate (<0.05 or <0.01). Binary logistic regression analysis revealed that AF was independently associated with HT (=2.527, 95%:2.030-3.146, <0.01).@*CONCLUSIONS@#AF is independently associated with the occurrence of HT in ischemic stroke patients treated with intravenous thrombolysis.

Analysis of intravenous thrombolysis time and prognosis in patients with in-hospital stroke / 浙江大学学报·医学版

OBJECTIVE@#To compare the time delay between in-hospital stroke and out-of-hospital stroke patients, and to explore the influence factors for the prognosis of in-hospital stroke patients treated by intravenous thrombolysis.@*METHODS@#Clinical data of 3050 patients with ischemic stroke who received intravenous thrombolysis in 71 hospitals in Zhejiang province from June 2017 to September 2018 were analyzed. Differences of time delay including door to imaging time (DIT), imaging to needle time (INT) and door to needle time (DNT) between in-hospital stroke (=101) and out-of-hospital stroke (=2949) were observed. The influencing factors for the outcome at 3 month after intravenous thrombolysis in patients with in-hospital stroke were analyzed using binary logistic regression analysis.@*RESULTS@#Patients with in-hospital stroke had longer DIT[53.5 (32.0-79.8) min vs. 20.0 (14.0-28.0) min, <0.01], longer IDT[47.5(27.3-64.0)min vs. 36.0(24.0-53.0)min, <0.01], and longer DNT[99.0 (70.5-140.5) min vs. 55.0 (41.0-74.0) min, <0.01], compared with patients with out-of-hospital stroke; patients in comprehensive stroke center had longer DIT[59.5(44.5-83.3) min vs. 37.5(16.5-63.5) min, <0.01], longer DNT[110.0(77.0-145.0) min vs. 88.0 (53.8-124.3) min, <0.05], but shorter INT[36.5(23.8-60.3)min vs. 53.5 (34.3-64.8) min, <0.05], compared with patients in primary stroke center. Age (=0.934, 95% 0.882-0.989, <0.05) and baseline National Institute of Health Stroke Scale score (=0.912, 95% 0.855-0.973, <0.01) were independent risk factors for prognosis of in-hospital stroke patients.@*CONCLUSIONS@#In-hospital stroke had longer DIT and DNT than out-of-hospital stroke, which suggests that a more smooth thrombolysis process of in-hospital stroke should be established.

Effect of different working time on the prognosis of ischemic stroke patients undergoing intravenous thrombolysis / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis.@*METHODS@#Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively.@*RESULTS@#There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all >0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all >0.05).@*CONCLUSIONS@#The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.

Cloning and regulation of pig estrogen related receptor β gene (ESRRB) promoter / 生物工程学报

The estrogen related receptor family member Esrrb (Estrogen related receptor β) is a gene that expresses in the early stage of embryo and plays an important role in the core pluripotent network. Its function has been analyzed in human and mouse, although no report so far related to pig. Therefore, to explore its mechanism of transcriptional regulation and expression pattern, we cloned a 3.3 kb pig ESRRB promoter by PCR and constructed the green fluorescence protein (GFP) reporter vector pE3.3. We used these vectors to study the ESRRB expression pattern in 293T, Hela and C2C12. Sequence was analyzed for regulatory elements that share homology to known transcription factor binding sites by TFSEARCH and JASPER program. Some pluripotency related genes such as SMAD, STAT3, MYC, KLF4 and ESRRB have been found within the 3.3 kb sequence by co-transfected pig ESRRB promoter and these potential regulators. We found that ESRRB only expressed in 293T and SMAD could activate ESRRB expression obviously. To determine the core promoter region, a series of ESRRB promoter fragments with gradually truncated 5'-end were produced by PCR and inserted into pGL3-Basic vector. After transient transfection into 293T, dual luciferase assay was used to measure these promoter activities. The result suggested that the core promoter of pig ESRRB located within -25 bp to -269 bp region. These results suggest that these transcription factor binding sites and the core promoter region may be essential for transcriptional regulation of pig ESRRB gene.

Anti-tumor activity of safflower polysaccharide (SPS) and effect on cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the anti-tumor activity of SPS in vivo and in vitro and the cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice.</p><p><b>METHOD</b>The transplanted tumor model of S180 Sarcoma was established with KM mouse. The SPS was adminished i.p. for 10 d, the tumor weight was detected. The transplanted tumor model of LA795 lung cancer was established with T739 mouse and SPS was adminished i.p. for 10 d and the tumor weight and the cytotoxicity of CTL cells, NK cells were detected. The Anti-tumor activity of SPS on three types of tumor cells in vitro was observed with trypan blue exclusion staining.</p><p><b>RESULT</b>SPS 40 mg x kg(-1) can significantly inhibit the growth of S180 Sarcoma in mice and inhibitory rate was 51.33% (P<0.01). It can also inhibit the growth of LA795 lung cancer in mice and the tumor volume was reduced obviously for 3.29 mm3 (P<0.05). It can remarkably enhance the cytotoxicity of splenic CTL cells, NK cells in tumor-bearing (P<0.05).</p><p><b>CONCLUSION</b>SPS have anti-tumor effects, the mechanism of the anti-tumor activity may be related to enhance the cytotoxicity of CTL cell and NK cell.</p>

The molecular mechanisms for mouse's neoplasm apoptosis triggered by lotus GFW / 中国免疫学杂志

Objective:To study on GFW-inducing tumor apoptosis and to find the experimenting basis for utilizing GFW in cancei theiapy.Methods:S180 mouse sarooma model was used to detect inhibiting effects of GFW on tumor grouth in viro,Morphological changes were observed by electron microscopy and flow cytometer was used for determination apoptosis.The protein expression of p21 and the mRNA expression of Survivin were evaluated by immunohistochemistry and in situ hybridization.Results:For S180 sarcoma ,the inhibiting rate of GFW was 38.93%.Apoptosis was 17.79% detected by flow cytomety.Typical apoptotic cells and apoptotic bodies were observed through electron microscope. Chromatin was found gathering as aggregates in nucleus or under nucleus membrane and the nuclear body formed at the same time. Survivin mRNA decreased markedly in the GFW group when compared with the model group(P

An Inquiry into Preparing Diarrhea Model of Mice and Application of Diarrhea Index / 中草药

In Order to screen antidiarrhea drugs, the standard operation of mice diarrhea model replicated with leave of Cassia angustifolia vahl was introduced. In experiments, diarrhea index expressed with loose stool ineidence rate multiplied by loose stool grade was used as main index. It thoroughly mirrors indi. vidual diarrhea degree and possesses comparability. The result indicates that diarrhea index in mice presented normal distribution. The index between animal model groups kad no difference as well as no differcnce was found in model mice of same group for six consecutive days, with good reproduclbility. It is recommended that the model can be used for the screening of antidiarrhea drugs.

Guizhi Fuling Wan's effect on the expression of P21~(waf/cip) in bearing tumor mice / 西安交通大学学报(医学版)

Objective To study the effect of Guizhi Fuling Wan(GFW) on tumor apoptosis and apply the experimenting basis of GFW's development and utilization.Methods The S180 mice sarcoma model was used to detect the inhibitory effects of GFW,observe the ultrastructural change by electron microscopy,and the flow cytometer was used for apoptosis determination.The protein expression of P21waf/cip and the mRNA expression of Survivin were evaluated by immunohistochemistry and in situ hybridization.Results For S180 sarcoma,the inhibition ratio of GFW was 38.93%.The apoptosis was 17.79% by the flow cytometer.Some typical apoptotic cells and apoptotic bodies were observed through electron microscope.Chromatin gathered at the side of cell,the nucleus turned into the nucleus band and nucleus projected.Survivin mRNA markedly declined in the GFW group when compared with that in the model group(P