Effect of Modified Chaihu Shugansan on Gallbladder Function and Inflammatory Cytokines Levels in Treatment of Chronic Cholecystitis Cholelithiasis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and influence of modified Chaihu Shugansan combined with ursodeoxycholic acid tablets on inflammatory factors in treatment of chronic cholecystitis cholelithiasis （stagnation of liver and gallbladder Qi）. Method:One hundred and ten patients were randomly divided into control group （60 cases） and observation group （60 cases）. Both groups received lifestyle intervention， and oral ursodeoxycholic acid tablets， 50 mg/time， taken in the morning and evening meals. Patients in control group additionally took Yidanshu capsules orally， 4 capsules/time， 3 times/day. Patients in observation group additionally took modified Chaihu Shugansan orally， 1 dose/day. The treatment courses continued 3 months in both groups. Before and after treatment， traditional Chinese medicine （TCM） symptom scores were graded， the ultrasound status of chronic gallbladder inflammation， gallbladder contraction function and stones was graded， the levels of interleukin-6 （IL-6）， IL-8， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and nuclear transcription factor-<italic>κ</italic>B（NF-<italic>κ</italic>B）Were detected， and safety was evaluated. The efficacy for TCM syndromes， imaging efficacy and the efficacy for eliminating gallbladder stones were compared between the two groups. Result:The efficacy for TCM syndrome， efficacy on color ultrasound for chronic cholecystitis and the efficacy on imaging for cholelithiasis in the observation group were all better than those in the control group（<italic>Z</italic>=2.104<italic>，Z</italic>=2.076，<italic>Z</italic>=2.101，<italic>P</italic><0.05）. The thickness of gallbladder wall and volume of the gallbladder of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， and gallbladder contraction function was higher than that in control group （<italic>P</italic><0.01）. Levels of IL-6， IL-8， TNF-<italic>α</italic> and NF-<italic>κ</italic>B in observation group were lower than those in control group （<italic>P</italic><0.01）. Conclusion:modified Chaihu Shugansan combined with ursodeoxycholic acid in the treatment of chronic cholecystitis and cholelithiasis （liver and gall Qi stagnation） is better than Yidanshu capsule combined with ursodeoxycholic acid sour scheme in terms of clinical efficacy， imaging efficacy， and elimination of gallbladder stones. It can reduce inflammation， and enhance gallbladder contraction， with high safety in clinical use.

Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis

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.

Association of Lipoprotein-Associated Phospholipase A2 with Characteristics of Vulnerable Coronary Atherosclerotic Plaques

PURPOSE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques. MATERIALS AND METHODS: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. RESULTS: Lp-PLA2 concentration was significantly higher in both UA and SA patients [(396+/-36) microg/L and (321+/-39) microg/L, respectively] compared with the controls [(127+/-49) microg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91+/-0.15 vs. 0.85+/-0.11, p=0.005) and eccentricity index (EI) (0.73+/-0.16 vs. 0.65+/-0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91+/-0.23) mm vs. (0.63+/-0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSION: Serum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.

Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To investigate the effect of berbamine on human hepatoma cell line SMMC7721.</p><p><b>METHODS</b>The effects of 24 h and 48 h incubation with different concentrations (0 to approximately 64 microg/ml) of the berbamine on SMMC7721 cells were evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst 33258 staining was conducted to distinguish the apoptotic cell, and the appearance of sub-G1 stage was determined by PI (propidium iodide) staining, the percentage of apoptotic cell was determined by flow cytometry following annexin V/PI staining. Flow cytometry was performed to analyze the cell cycle distribution and the mitochondrial membrane potential (psi(m)); the expression of activated caspase3 and caspase9 was analyzed by Western-blot.</p><p><b>RESULTS</b>The proliferation of SMMC7721 was decreased after treatment with berbamine in a dose- and time-dependent manner. Berbamine could induce apoptosis in SMMC7721 cells and could cause cell cycle arrest in G0/G1 phase, to induce loss of mitochondrial membrane potential (psi(m)) and activate caspase3 and caspase9. Berbamine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk.</p><p><b>CONCLUSION</b>Berbamine exerts antiproliferative effects on human hepatocellular carcinoma SMMC7721 cells. The anticancer activity of berbamine could be attributed partly to its inhibition of cell proliferation and induction of apoptosis in cancer cells through loss in mitochondrial transmembrane potential and caspase activation.</p>

siRNA inhibits efgl7 expression in human endothelial cell line HUVEC / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of small interference RNA (siRNA) on epidermal growth factor-like domain 7 (egfl7) gene expression in human endothelial cell line HUVEC.</p><p><b>METHODS</b>siRNA targeting egfl7 (siRNA1, siRNA2, siRNA3 and siRNA4) was constructed through online design of Amnion company and transfected into human endothelial cell line HUVEC with lipofectamine. The nontransfected cells and cells treated with control siRNA were taken as controls. At 24, 48 and 72 hours post various interventions, cell viability was determined by MTS method as well as LDH and ATP releasing tests. egfl7 expressions at protein and mRNA levels were detected by Western blot and RT-PCR respectively.</p><p><b>RESULTS</b>Cell survival rate, LDH and ATP release were significantly reduced in siRNA treated cells compared to control cells (P < 0.05). Similarly, egfl7 expression at protein and mRNA levels was also significantly reduced in siRNA treated cells (P < 0.01), especially in siRNA1 treated cells.</p><p><b>CONCLUSION</b>siRNA inhibited egfl7 gene expression and cell survival in HUVEC.</p>

Plasma activated coagulation factor VII and Msp I polymorphism in elderly patients with coronary heart disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of activated coagulation factor VII(F7a) and its gene Msp I polymorphism with coronary heart disease in elderly patients.</p><p><b>METHODS</b>This was a case-control study, and the method of candidate gene was adopted. F7 genotypes were identified with polymerase chain reaction amplified genomic deoxyribonulieic acid (DNA) and Msp I restriction fragment length polymorphism analysis, and the level of plasma F7a was detected with recombinant tissue factor method for 108 elderly patients with coronary heart disease and 120 sex- and age-matched healthy control subjects.</p><p><b>RESULTS</b>(1) Plasma F7a levels was significantly higher in elderly patients with coronary heart disease than in healthy control subjects (2.88 +/- 0.62 vs 2.58 +/- 0.60 microg/L, P < 0.05), and was significantly higher in old myocardial infarction than in stable angina pectoris (3.12 +/- 0.62 vs 2.76 +/- 0.60, P < 0.05). F7a was shown to be a risk factor for coronary heart disease in elderly patients by Logistic regression analysis (OR=1.21 P < 0.05). (2) The allelic frequencies were in accordance with Hardy-Weinberg equilibrium. The results suggested that the distribution of genotype and allelic frequencies in the groups displayed no significant difference, and there was no difference between the subgroups of coronary heart disease in elderly patients, either (P > 0.05). (3) F7a level was significantly higher in RR genotype than in Q allele carriers (2.72 +/- 0.60 vs 1.98 +/- 0.59 microg/L, P < 0.05) and was associated with F7 gene polymorphism.</p><p><b>CONCLUSION</b>Plasma F7a level may be an independent risk factor of coronary heart disease in elderly patients, and it may be influenced by the Msp I polymorphism of F7 gene.</p>

Relationship between drug resistance and the expression of NF-kappaB induced in leukemic cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To explore the relationship between drug resistance of leukemic cells and the expression of both IkappaB-alpha and NF-kappaB associated with apoptosis induced by arsenic trioxide (As2O3) in K562 and K562/ADR cells.</p><p><b>METHODS</b>Apoptosis was induced in K562 and K562/ADR cells cultured with As2O3 in different concentrations. Western blot was used to analyze the expression of NF-kappaB in nuclear and IkappaB-alpha in cytoplasm of these cells. Apoptosis and degradation of IkappaB-alpha protein were also observed by flow cytometry.</p><p><b>RESULTS</b>After exposure to As2O3, the ratio of apoptosis cells in K562/ADR was significantly lower than that in K562 cells. K562/ADR [(6.33+/-1.51)%] and K562 cells [(13.25+/-1.83)%] cultured with 1 micromol/L As2O3 were in apoptosis. When cultured with 4 micromol/L As2O3, the apoptosis cells increased to (8.00+/-1.47)% and (50.56+/-8.62)%, respectively. The level of IkappaB-alpha in K562 cytoplasm was down-regulated from 88.07% to 49.21% after As2O3 stimulation, while NF-kappaB in nuclear was up-regulated, that was not found in K562/ADR cells.</p><p><b>CONCLUSION</b>As2O3 could induce apoptosis of K562 cells, associated with the degradation of IkappaB-alpha and the activation of NF-kappaB. There are an elevated expression of NF-kappaB and resistance to apoptosis induced by As2O3 in K562/ADR cells.</p>

Baicalein selectively induce apoptosis in human leukemia K562 cells / 药学学报

<p><b>AIM</b>To study the antitumor effect of baicalein on human leukemia K562 cell and its mechanism.</p><p><b>METHODS</b>The IC50 value and cytotoxity of K562 cell were detected by MTT method. The apoptotic cell was analyzed by FCM using Annexin V FITC--PI staining method. Sub-G1 peak was also measured by FCM. Protein expressions of Bcl-2, Fas, Caspase 3 were evaluated with FCM.</p><p><b>RESULTS</b>Baicalein was shown to significantly inhibit the proliferation of K562 cell in a dose-dependent manner and selectively induce apoptosis of human leukemia K562 cells. Flow cytometric analysis showed that baicalein arrested K562 cells in the S phase. In addition, protein expression of Fas, Caspase 3 of K562 cells increased after exposure to baicalein, but Bcl-2 was unchanged.</p><p><b>CONCLUSION</b>Baicalein can selectively induce apoptosis of human leukemia K562 cell dose and time dependently through up-regulation of caspase-3 and fas gene expression level.</p>

Isolation, culturation and adipogenisis committed differentiation of adult human mesenchymal stem cell / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To isolate MSCs from adult human bone marrow cells and to induce them into adipocytes.</p><p><b>METHODS</b>MSCs were isolated from adult human bone marrow aspirated by Percoll and expanded in L-DMEM. The surface antigen of MSCs, CD14, CD34, CD45, CD44, VLA-1, HLA-DR and cell cycle were analysed on a FACScan flow cytometer. MSCs were cultured in adipogenisis inducing medium including insulin, 1-methyl-3-isobutylxanthine, indomethine and dexamethasone for 7 days and stained with Oil Red O.</p><p><b>RESULTS</b>MSCs grew as adherent cells and expanded more than 10 passages. They were positive for CD44 and negative for CD14, CD34, CD45, HLA-DR. The expression of VLA-1 was weak. After 7 days of adipocyte inducing, about 85%of the cells displayed accumulation of lipid vacuoles, as detected by Red Oil O.</p><p><b>CONCLUSION</b>MSCs isolated and cultured from adult human bone marrow can be induced to adipogenisis committed differentiation.</p>

The effect of physical training on insulin resistance in patients with chronic heart failure / 中华物理医学与康复杂志

Objective To investigate insulin resistance and the effect of physical training on it in the pa- tients with chronic heart failure (CHF). Methods One hundred and twenty NYHAⅡ-ⅢCHF patients were ran- domly divided into a training group( n = 65 ) and a routine therapy group (n = 55 ). Another 35 healthy subjects were recruited as control group. All the patients were treated with routine anti-CHF drugs, and the training group patients had received physical training twice a day in addition. The HOMA-IR, insulin sensitivity index (ISI) , left ventricu- lar ejection fraction (LEVF), left ventricular fractional shortening( LVFS), 6-minute walking distance, heart rate and mean blood pressure were compared between the training and routine therapy groups before and after physical ex- ercise in both groups, and a comparison was made between the patients and the controls before the intervention with regard to HOMA-IR and ISI. Results Comparing with control group, ISI was reduced while the HOMA-IR in- creased (P

Changes in NT-proBNP after physical training in patients with chronic heart failure / 中华物理医学与康复杂志

Objective To investigate the effect of physical training on plasma N-terminal pro-brain natri- uretic peptide(NT-proBNP)levels in patients with chronic heart failure(CHF).Methods Eighty NYHAⅡ-ⅢCHF patients were randomly divided into a training group(n=42)and a control group(n=38).A 6-minute walk- ing test was performed within 24 hours after the patients were admitted.The 6-minute walking distance and plasma NT-proBNP levels were determined before and after 8 weeks of programmed physical training.The patients of both groups were treated with routine drugs for heart failure.6-minute walk training was only performed in the training group twice a day for 8 weeks.Results Physical training could significantly reduce plasma NT-proBNP levels and improve performance on the 6-minute walking test.Conclusions Physical training could significantly reduce plas- ma NT-proBNP levels and improve the motor function of patients with CHF,and could be helpful in delaying the de- velopment of CHF.