n-Octanol/ water partition coefficients (Kow ) is an important parameter commonly used to explain toxicity, activity and transmembrane of drugs. However, it is difficult to be detected by direct experimental determination. In this work, a set of 29 neutral and acidic analogues of naphthalene and anthraquinone with reliable experimental Kow data was chosen as model compounds for establishing linear relationship between the logarithm of apparent n-octanol/ water partition coefficient (lgKow), and the logarithm of reversed phase-high performance liquid chromatography (RP-HPLC) retention factor of the solutes corresponding to neat aqueous fraction of mobile phase (lgkw ) as the quantitative structure-retention relationship (QSRR) model. Methanol-water mixture was used as mobile phase at various pH, and retention time (tR ) was rectified by a dual-point retention time correction (DP-RTC) in this method. The experiment results indicated that the proposed QSRR model had good correlation coefficient R2 = 0. 974 -0. 976 with satisfactory results of internal and external validation (the cross-validated correlation coefficient R2cv of 0. 970-0. 973, and 1. 4% ≤relative error (RE)≤7. 9% for all the 6 verification compounds). In addition, this QSRR model was compared with linear solvation energy relationship ( LSER) involved in different descriptors of molecular structure, showing no differences. The QSRR model was applied to measure Kow of 11 naphthalenes and anthraquinones, and the predicted data were compared with Shake-flask method (SFM) experimental ones, as well as calculated ones obtained by software. The results suggested that the proposed method for Kow determination in this work was more accurate, simple and fast. To the best of our knowledge, this is the first report on measuring Kow data for these compounds. The proposed strategy provides the possibility in determining Kow of lipophilic components in complex mixture more quickly and accurately by RP-HPLC.

Objective To investigate the relationships of nuclear factor кB (NF-кB) activation with protein kinase B (Akt) and glycogen synthase kinase 3β (GSK-3β) during amyloid-β (Aβ) (25-35) -induced apoptosis in pheochromocytoma cells (PC12 cells) of rats. Methods Apoptosis in PC12 cells was induced by A(25-35). The activities of Akt, GSK-3β and NF-кB were analyzed in this process. The Akt and GSK-3β pathways were blocked by their specific inhibitors, respectively, and the relationships of Akt and, GSK-3β with NF-кB during Aβ(25-35)-induced apoptosis in PC12 cells were determined. Results Aβ(25-35) induced apoptosis was in a dose-dependent manner. With 0, 5, 10, 20 μmol/L and 40 μmol/L Aβ(25-35) treaing for 48 h, the apoptosis rates of PC12 cells were (3. 01 ± 0.03)%, (3.08 ±0.03)%, (25.32 ± 0.76)%, ( 42.88 ± 0.60 )% and ( 60.85 ± 2.39 )% , respectively. Compared to control, both Akt and GSK-3β were suppressed during apoptosis, at meantime NF-кB was activated. The inhibited Akt activity by wortmannin leaded to decreased NF-кB activatity and increased GSK-3β activatity. Suppression of GSK-3β with its specific inhibitor LiCl caused the decreased activation of NF-кB too, but it had no significant influence on Akt activity. Conclusions These results suggest that both Akt and GSK-3β are upstream regulators of NF-кB. They co-regulate the activation of NF-кB during Aβ(25-35)-induced apoptosis in PC12 cells. This study contributes to the theoretical base for the pathogenesis of Alzheimer disease (AD) , and provides a new idea to AD prevention and therapy.

Objective To evaluate the clinical value of different radiotherapy protocols in the treatment of advanced cervical cancer. Methods From 1976 to 2006,763 patients with stage Ⅲ cervical cancer(722 with squamous cell carcinoma and 41 with adenocarcinoma)were treated by radiotherapy in our hospital. 113 patients were treated by two-field whole pelvic irradiation in conventional fractionation plus brachytherapy (CF group), 44 by four-field whole pelvic irradiation in accelerated hyperfractionation plus brachytherapy( AHF group), and 606 by concomitant four-field unconventional fractionation radiotherapy and brachytherapy(FRT group). Sixty-one patients were treated by radiotherapy and chemotherapy. Among 350 patients who had complete data, the short-term efficacy and toxicities were compared. Results For patients in CF,AHF and FRT groups, the 3-year overall survival rates (OS) were 65.7%, 66.8% and 44.3%, respectively (P=0.000), and the 5-year OS were 65.7 % ,66.8 % and 36.3 %, respectively (P=0.000). The 10-year OS were 43.3% and 31.9% in CF and FRT groups(P=0.200). For squamous cell carcinoma,the OS was higher of patients with chemotherapy than those without. In 350 patients who had complete data,the local control rates of CF, AHF and FRT groups were 83.0% ,93.2% and 86.1%, respectively(X2=2.70, P=0.259);AHF group had the lowest side effect rate, especially skin reaction (9.1%,X2=20.25,P=0.002) ;CF group had the lowest acute bone marrow suppression rate(X2=25.95,P=0.000);for squamous cell carcinoma, the OS was higher in patients with chemotherapy than those without;the acute bone marrow and intestinal toxicities were more in patients with chemotherapy than those without. Conclusions CF and AHF groups have similar 5-year OS of patients with advanced cervical cancer. AHF group has less toxicities, shorter treatment course and a trend of better local control. Concurrent chemoradiation could improve survival and local control of the patients with advanced squamous cell cervical cancer while increase the side effects. The individual condition should be considered to choose the treatment protocol.

Objective To investigate the fungal infection situation and the risk factors in lupus nephritis(LN)patients.Methods Infection states were investigated in 93 LN patients and 45episodes(about 48.4%) occurred the different kind and different degree of Hospital-acquired infections.The fungal infection rate was 22.6% and two patients directly died of it.Except fungi,the main pathogens were bacteria and virus.The main infection sites were urinary,gastrointestinal and respiratory tract.Results The infection causes were related to the use of corticosteroids,immunodepressive,antibiotic and the aggressive operation,renal failure ,the duration in hospital and so on.Conclusion Effective prevention and treatment for infection in LN patients is an important way to improve the prognosis of LN.

Objective To investigate the level and the source of inflammatory factors in patients with paroxysmal atrial fibrillation.Methods Thirty patients with paroxysmal atrial fibrillation were selected as observation group,and 20 cases of patients with paroxysmal supraventricular tachycardia were selected as control group.The blood samples of coronary sinus,right atria,left atria and femoral vein were consecutively collected during the procedure of radiofrequency ablation.The level of tumor necrosis factor (TNF)-α,soluble tumor necrosis factor receptor-1 (sTNFR1),and interleukin(IL)-6 was detected by ELISA separately and compared between two groups.Results The level of TNF-α and IL-6 of coronary sinus,right atria,left atria and femoral vein in observation group was significantly higher than that in control group [TNF-α:(4.45 ± 1.76) ng/L vs.(0.59 ± 0.36) ng/L,(6.67 ± 1.43) ng/L vs.(0.51 ± 0.30) ng/L,(8.35 ± 2.03) ng/L vs.(0.85 ± 0.50) ng/L,(9.97 ± 2.70) ng/L vs.(0.28 ± 0.29) ng/L,P=0.000;IL-6:(2.02 ± 0.87) ng/L vs.(1.04 ± 0.63) ng/L,(1.51 ± 0.68) ng/L vs.(0.74 ± 0.26) ng/L,(2.00 ± 0.51) ng/L vs.(0.88 ± 0.35) ng/L,(1.32 ±0.47) ng/L vs.(0.48 ±0.28) ng/L,P =0.000].The level of high sensitivity C reactive protein (hs-CRP) in observation group was significantly higher than that in control group [(2.41 ± 1.35) mg/L vs.(1.10 ±0.53) mg/L,P =0.002].The level of TNF-αof left atrium in observation group was significantly higher than that of other three sites (P=0.000).The level of IL-6 in the coronary sinus and femoral vein was significantly increased,compared with that in the right atria and left atria (P ＜ 0.05).The level of sTNFR 1 in the femoral vein,right atria and coronary sinus difference was not statistically significant (P ＞ 0.05),but was significantly higher than that in the left atria(P ＜ 0.05).The level of TNF-α,IL-6 and hs-CRP was correlated with the diameter of left atrium (LAD) (P ＜ 0.01 or ＜ 0.05).The level of sTNFR1 in left atria was positively correlated with LAD,and the level of sTNFR1 in right atria was negatively correlated with LAD (P ＜ 0.01).Conclusions The level of TNF-α,IL-6 and hs-CRP is increased in patients with paroxysmal atrial fibrillation.TNF-α and IL-6 may come from the heart and is related with the enlargement of left atrium.

AIM: To investigate the effect of high glucose concentration on serum and glucocorticoid induced protein kinase (SGK) mRNA and protein expressions in human proximal tubular epithelial cells (HKC) and the possible role of SGK in the production of extracellular matrix (ECM) of HKC under the condition of high glucose. METHODS: HKC was divided into 3 groups: control glucose group (CG group, 5 5 mmol/L D-glucose); high glucose group (HG group, 25 mmol/L D-glucose) and osmotic control group (MG group, 19 5 mmol/L mannitol and 5 5 mmol/L D-glucose). The expressions of SGK mRNA and protein were assessed by semi-quantitative RT-PCR and Western blotting respectively. The level of secretary and cytoplasmic fibronectin (FN) were detected by enzyme-linked immunoabsordent assay (ELISA) and indirect-immunofluorescence. RESULTS: HKC expressed SGK1, SGK2 and SGK3 at mRNA and protein levels. Their mRNA level were up-regulated since 2 hours after cells exposed to D-glucose and this up-regulation persisted to the end of 8th hour, and SGK1 protein level elevated simultaneously. On the other hand, the increased FN secretion by high glucose was in a time-dependent manner and its improved secretion threshold was just followed by the high expression of SGK1. CONCLUSIONS: In response to high glucose, the expression of SGK1, SGK2 and SGK3 in human proximal tubular epithelial cells were up-regulated which was accompanied with FN accumulation. The high expression of SGK may mediate overproduction of ECM in proximal tubular epithelial cells and contribute to the diabetic nephropathy.

AIM: To investigate alteration of inward re ctifier potassium current (I K1) in atrial myocytes and mRNA expression of gene Kir2.1 encoding I K1 in atrial myocardial tissue in patients with chronic atrial fibrillation (AF) compared to that with sinus rhythm (SR).METHODS: Single myocytes were isolated by enzymatic dissociation with the chunk method an d the ionic current was recorded using whole cell patch clamp technique. The sem i-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of Kir2.1 in atrial myocardial tissue, and the g ene GAPDH was used as an internal control.RESULTS: (1) The I K1 density was increased in AF group at hyperpolarizing pot entials, at -120 mV the current densities was (-5.71?0.65) pA/pF in AF group (n=28 cells from 7 patients) and (-4.26?1.22) pA/pF in SR group (n=35 cells from 9 patients) (P0.05).CONCLUSIONS: The increase in I K1 at hyperpolarizing potentials may be related to th e atrial electrophysiological remodeling in chronic human AF. The increased I K1 density in atrial myocytes in AF group without alteration of Kir2.1 mRNA expression in atrial tissue suggests that I K1 may be mediated at post-transcriptional levels.

In order to investigate the effect of ligustrazine (Lig) i.p. on peritoneal permeability in peritoneal dialysis and its side effects, creatinine was given intravenously and continuously to maintain the high plasma creatinine level. All the rabbits were divided into three groups: normal control group (group A), group B treated with 0.12% Lig and group C treated with 0.24% Lig. The peritoneal dialysis of all rabbits lasted 2 h. The plasma and dialysate levels of glucose, protein and creatinine were observed immediate, 30 min, 60 min, 90 min, 120 min after dialysis. Creastinine dialysate/plasma ratio (D/P), protein D/P ratio, glucose D/Do at different time points after dialysis and creatinine mass transfer area coefficient (MTAC) at 120 min were calculated. The structures of peritoneum were observed under optical microscope and electron microscope after continuously intraperitoneal injection of Lig for 14 days. The results showed that the 90-min and 120-min creatinine D/P ratios in the group C were higher than in the group A. The 120-min creatinine MATC in the group C was higher than in the group A. The rabbits treated with Lig did not show significant structure changes of peritoneum and signs of peritoneal irritation. It was suggested that Lig could increase mass transfer ability of peritoneum without significant side effects.
Biological Transport ; Cell Membrane Permeability ; Creatinine/blood ; Dialysis Solutions/chemistry ; Peritoneal Dialysis/*methods ; Peritoneum/*metabolism ; Pyrazines/*pharmacokinetics ; Pyrazines/pharmacology

This study investigated the variation of serum monocyte chemoattractant protein-1 (MCP-1) in patients with both diabetes mellitus (DM) and metabolic syndrome (MS). Based on the International Diabetes Federation (IDF) diagnostic criteria, 93 patients enrolled in this study were divided into four groups: normal control (NC), simple DM, simple MS, and DM plus MS (DM-MS) groups. The main measures included height, weight, waist circumference (WC), hip circumference, blood pressure, fasting blood glucose, insulin resistance index (HOMA-IR), serum triglyceride (TG), HDL-ch, LDL-ch, and MCP-1. The results showed that the serum levels of MCP-1 in the DM-MS group were significantly increased as compared with those in the DM and MS groups (P<0.05), and the increase in the MCP-1 level in the DM group was much higher than in the MS group (P<0.05). The DM-MS group had the highest HOMA-IR levels, followed by MS, DM and NC groups (P<0.05). Correlation tests showed that the association of MCP-1 with age, HDL-ch, or LDL-ch was insignificant, whereas that of MCP-1 with body mass index (BMI), waist hip rate (WHR), WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), TG, and HOMA-IR was significantly positive. It was concluded that circulating MCP-1 was substantially increased in patients with both DM and MS as compared with that in the patients with DM or MS alone, and the central obese state may contribute to a more vicious proinflammatory condition and insulin resistance in patients with diabetes.

To investigate the expression and the role of three isoforms of Serum and Glucocorticoid-inducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.