OBJECTIVETo study the effect of Buyang Huanwu Decoction (BHD), Xuefu Zhuyu Decoction (XZD), and Sijunzi Decoction (SD) contained serums on expressions of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signals, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and to explore possible anti-atherosclerotic mechanisms.

METHODSTwenty New Zealand rabbits were divided into 4 groups at random, i.e., the normal control group, the BHD group (6.7 g/kg), the XZD group (3.6 g/kg), and the SD group (1.6 g/kg), 5 in each group. All medication lasted for 7 successive days. Two h after the final medication, about 50 mL blood was withdrawn from rabbit heart for preparing serums. Human umbilical vein endothelial cell ECV304 were cultured in vitro for 18 h and randomly divided into the blank control group, the model group, the Western medicine (WM) control group, the BHD group, the XZD group, and the SD group at random. ECV304, except in the blank control group, were stimulated with lipopolysaccharide (LPS) for 2 h. Those in the WM control group and CM groups were treated respectively with corresponding CM contained serum for 24 h. Finally gene and protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor-6 (TRAF-6), NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 were detected by fluorescent quantitative PCR and Western blot.

RESULTSCompared with the blank control group, mRNA expressions of TLR4, MyD88, TRAF-6, NF-KB, LOX-1 , TNF-cx, ICAM-1, and VCAM-1 increased significantly; protein expressions of TLR4, NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 also increased significantly in the model group (P < 0.01). Compared with the model group, mRNA and protein expressions of each index could be significantly inhibited in the BHD group, the XZD group, and the WM control group (P < 0.05). Besides, mRNA and protein expressions of each index could be significantly elevated more in the BHD group and the XZD group than in the WM control group (P < 0.05). No statistical difference existed in each index between the SD group and the rest groups (P > 0.05).

CONCLUSIONSThe mechanism of BHD and XZD for fighting against atherosclerosis might be associated with inhibiting TLR4/NF-κB signal transduction pathway and expressions of its downstream inflammatory factors such as LOX-1, TNF-α, ICAM-1, and VCAM-1. But SD showed no associated effect on atherosclerosis.

Animals ; Atherosclerosis ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelial Cells ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipopolysaccharides ; Myeloid Differentiation Factor 88 ; metabolism ; NF-kappa B ; metabolism ; Rabbits ; Scavenger Receptors, Class E ; Signal Transduction ; TNF Receptor-Associated Factor 6 ; metabolism ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Umbilical Veins ; Vascular Cell Adhesion Molecule-1 ; metabolism

To elucidate the signal transduction mechanism of systemic inflammatory response syndrome induced by LPS,Western blot analysis was used to assay the protein expression and phosphorylation levels of ERK, JNK,and p38 MAPK in murine KC which were stimulated by LPS. It was found that LPS treatment resulted in no significant change in their protein expression, but a rapid transient increase in their phosphorylation levels, which peaked at 30, 45,and 20 minutes,respectively; The values returned to mear baseline within 2 hours. Kinase phosphorylation levels of these three MAPKs induced by LPS were found to be dose dependent in a range of 10 pg/ml to 100ng/ml. No phosphorylation was observed in unstimulated cells. Among them, p38 MAPK shoned fastest and highest phosphorylation levels. The results show that LPS can markedly activate ERK, JNK,and p38 MAPK in KC, and p38 MAPK may play a more important role in LPS induced kupffer cell activation than ERR and JNK.

Objective To evaluate the efficiency of interventional treatment for primary liver cancer with spontaneous rupture. Methods Three cases of spontaneous rupture of primary liver cancer were undertaken hepatic arterial chemoembolization with prior chemo-infusion and followed by gelfoam partical and stripes for embolization Results 3 cases of massive type of primary liver carcinoma with spontaneous rupture were all successfully once embolized, including one with additional super liquefied lipiodal as embolic agent who has been survived for more than 20 months. Conclusions Hepatic arterial chemo-embolization shows prominent hemostasis during emergency for spontaneous rupture of primary hepatic carcinoma providing double effectiveness of hemostasis and treatment.

OBJECTIVE:To establish an overall teaching evaluation system for clinical pharmacology with PBL(problem-based learning) mode. METHODS:The teaching evaluation system was established by“Delphi”method,and it has been applied to 270 students at China Medical University in 2013-2014. RESULTS:According to the result of test score,PBL method can improve abil-ity of analyzing medical records,while formative evaluation indicates most of the students are satisfied with class response.And PBL method also can enhance student’s skill of clinical practice,broaden the knowledge an so on. CONCLUSIONS:The evaluation sys-tem was comprehensive with contents,systematic and objective,and it also can provide an effective feedback in teaching,which can accelerate the optimization of the teaching mode and improve the quality of education.

Esophagus ; Foreign Bodies ; Humans ; Infant ; Male

Objective To investigate the effect of dietary fiber on carbohydrate metabolism of healthy volunteers after the intake of corn starch meal. Methods Totally 12 healthy volunteers aged (25. 8 ± 5. 3) years were enrolled in this study, and they were equally randomly divided into two groups (group A and group B). This was an open, randomized, cross-over, and two-period study, and each period lasted for one day. In period 1, the subjects in group A received fiber-free corn starch and group B received high-fiber corn starch (containing 16 g dietary fiber). In period 2, the two groups are crossed. There was a one-week wash-out time between the two study days. On the study day, breath samples of fasting and 0. 5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0,7. 0, 8. 0 hours post meal were collected to measure13 CO2. Results The delta over baseline at 0. 5, 1.5, 2. 0,2. 5, 3. 0, 4. 0 hour after test meal in fiber free group and in high fiber group were 0. 79, 2. 03, 2. 57, 2. 86,3. 02, 3. 18 and 0. 16, 1. 33, 1.77, 2. 10, 2. 34, 2.42, respectively (the P value was 0. 014, 0. 014, 0. 011,0.018, 0. 036, and 0.020, respectively). Peak concentration of delta over baseline of fiber free group and high fiber group was 3.18 and 2. 56 respectively, there was no significant difference between two groups (P > 0. 05) ,peak time of the group at 4. 0 hour and 3. 5 hour respectively, showed significant difference (P = 0. 032). The cumulative percentage dose recovered 0. 5-6. 0 hours after test meal in fiber-free group and in high-fiber group were 0.41, 1.46, 3.15, 5.50, 8.28, 11.30, 14.42, 17. 62, 23. 65, 28. 78 and 0. 09, 0. 55, 1.61, 3.22,5.23,7.53, 10.09, 12.68, 17.60, 22.27 respectively (the P value was 0.014, 0.018, 0.018, 0.014, 0.013,0.014, 0.018, 0.020, 0.025, and 0.044, respectively). However, there was no significant difference 6.0 hours after meal (P > 0. 05 ). Conclusion The dietary fiber used in this study can delay the absorption of carbohydrate 6. 0 hours within intake without influencing its total absorption amount.

Objective To study the effect of fosinopril on the expression of NADPH oxidase subunit p22phox mRNA and the extracellular matrix (ECM) accumulation in the kidneys of rats with diabetes mellitus . Methods Diabetic rats induced by streptozotocin were randomly divided into control group(DM group) and fosinopril group (fosinopril 10 mg'kg-1·d-1) (DM+Fosin group) and treated for 12 weeks . Expression of p22phox mRNA of NADPH oxidase in kidneys was measured by RT-PCR . The expression of fibroneetin was studied by immunohistochemistry and matrix metalloproteinases 9 activity was detected by Zymography . Meanwhile, the kidney hypertrophy index, serum creatinine level and 24-hour urinary protein excretion were evaluated . Results The expression level of p22phox mRNA in the kidneys of DM+Fosin group rats was decreased by 45% than that of DM group at week 4 (P＜0 .05) . At week 8 fosinopril significantly decreased the expression of glomerular and tubulointerstitial fibronectin by 52,5% and 42 .9% respectively (P＜0 .05), while increased MMP-9 activity by 29 .6% (P＜0 .05) compared with DM group . Fosinopril significantly decreased 24-hour urinary protein excretion of diabetic rats from week 8 . Serum creatinine level, 24-hour urinary protein excretion and kidney hypertrophy index were significantly decreased by 35 .9%, 50 .2% and 17 .2% in rats of DM+Fosin group than those of DM group at week 12 (P＜0 .05) . Fosinopril did not affect blood sugar significantly . Conclusion Fosinopril has beneficial effect on diabetic nephropathy partly through inhibiting the expression of NADPH oxidase p22 phox mRNA .

Objective To evaluate antimicrobial activity of fosfomycin combined with tigecycline against Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae and study the mechanism of drug resistance to fosfomycin. Methods Broth microdilution method was used to independently determine the minimum inhibitory concentrations (MIC)of fosfomycin and tigecycline against 42 Klebsiella pneumoniae isolates (including 20 KPC-producing and 22 KPC non-producing isolates).Checkerboard design method was applied to evaluate combined effect of different concentrations on antimicrobial susceptibility and calculate the fractional inhibitory concentration index (FICI).FICI=MICfosfomycin joint/MICfosfomycin monotherapy +MICtigecycline joint/MICtigecycline monotherapy .Related interpretation criteria were as following:FICI≤0.5 means synergy;0.5 2 means antagonism.The fosfomycin resistant genes in KPC-producing Klebsiella pneumoniae isolates were screened.The data were analyzed by t test.Results Antimicrobial susceptibility testing results indicated the fosfomycin and tigecycline susceptibility rates in KPC-producing isolates were 35 .0%(7/20)and 70.0% (14/20 ),respectively.The susceptibility rates of drug combination increased to 50.0% (10/20 )and 95 .0% (19/20 ),respectively,with both MIC decreased.MIC of tigecycline decreased significantly after combination therapy and showed a statistical significance compared with the MIC of monotherapy (t = - 2.596,P = 0.013 ),whereas there was no significant difference between single and combined therapy of fosfomycin (t=-1 .274,P =0.211).FICI indicated that a total of 60.0%isolates showed synergy and additive effects between two antimicrobial agents,followed by indifference (40.0%),but there was no antagonism effect.Among 22 KPC non-producing isolates,there were 54.5 %showing indifference effects,followed by additive (31 .8%)and synergy (13.6%)effects.No antagonism effect was found.The study also identified two isolates with fosA resistant gene which located on the same plasmid as well as the bla KPC gene.The plasmid sizes in the two isolates were 138.9 kb and 104.5 kb, respectively.Conclusions KPC-producing Klebsiella pneumoniae are more susceptible to tigecycline. Combined use of two antimicrobial agents mainly exerts synergy and additive effect rather than antagonism,which may suggest the combination therapy strategy could inhibit the activity of KPC-producing Klebsiella pneumoniae .

OBJECTIVETo investigate the effects of Yiqi Huoxue Compound (YHC) contained drug serum on the expressions of TLR4 and its downstream signal transduction pathway and LOX-1, TNF-alpha, ICAM-1 in human umbilical vein endothelial cells (HUVECs), and to study its possible anti-atherosclerosis (AS) mechanism. METHODS Twenty New Zealand rabbits were divided into 4 groups in random, i. e., the normal control group, the high concentration group, the middle concentration group, and the low concentration group, 5 in each group. Normal saline was given to rabbits in the normal control group by gastrogavage. High, middle, and low concentration of YHC was respectively given to rabbits in the rest 3 groups by gastrogavage for 7 successive days. The blood was withdrawn from the heart 2 h after the last gastrogavage. The serum was isolated after centrifuge. HUVECs was in vitro cultured and then randomly divided into 6 groups, i. e., the normal control group, the model group, the Western medicine control group, the high, middle, and low YHC groups. HUVECs were stimulated with LPS for 2 h, and then treated with high, middle, and low YHC contained serum. HUVECs were collected 24 h later. The gene expressions of TLR4, MyD88, TRAF-6, TRAM, TRIF, NF-kappaB, LOX-1, TNF-alpha, and ICAM-1 were detected using fluorescent quantitative PCR. The protein expressions of TLR4, MyD88, TRAF-6, and LOX-1 were determined using Western blot method.

RESULTSAfter HUVECs were stimulated by LPS, the expressions of TLR4, MyD88, TRAF-6, TRAM, TRIF, NF-kappaB, LOX-1, TNF-alpha, and ICAM-1 were enhanced, showing statistical difference when compared with the vehicle control group (P < 0.01). YHC contained serum significantly decreased the higher expressions of TLR4, MyD88, TRAF-6, NF-kappaB, LOX-1, TNF-alpha, and ICAM-1, showing statistical difference when compared with the model group (P < 0.05).

CONCLUSIONSYHC could inhibit the TLR signal transduction pathway and the expressions of LOX-1, TNF-alpha, and ICAM-1. These might be one of the mechanisms for treating various immune inflammatory diseases and preventing AS.

Animals ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; NF-kappa B ; metabolism ; Rabbits ; Scavenger Receptors, Class E ; metabolism ; Serum ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism