Theory of “combination of disease with syndrome” has been widely used in the establishment and evaluation of experimental animal models. The ulcerative colitis animal models with spleen-kidney yang deficiency pattern were established based on the theory according to complex factors. These models were not only required to show the features of “disease” and “syndrome” at the macro characterization, but also combined with microscopic biological indicators and prescription test so as to make comprehensive evaluation. But the problems in the establishment and evaluation of “combination of disease with syndrome” models hindered further development, such as the weak connection between disease and syndrome, multiplicity of models, and limitations in evaluation standards. Therefore, further improvement in the establishment and evaluation of models will make great sense to better ulcerative colitis animal models with spleen-kidney yang deficiency pattern.

OBJECTIVETo observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats.

METHODSA rat model of type 2 diabetes was established by high fat/sucrose diet combined with intraperitoneal injection of small dose streptozotocin (STZ) . Modeled rats were randomly divided into the model group, the ZQR group, and the metformin group, 8 in each group. Eight rats were recruited as a normal control group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150 mg/kg was administered to rats in the metformin group by gastrogavage. Equal volume of distilled water was administered to rats in the normal control group and the model group. All medication lasted for 12 weeks. The levels of fasting blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected. The body weight and wet liver weight were weighed, and the liver weight index calculated. The liver TG content was measured. The pathological changes of liver and the expression of SIK1 were observed by HE staining and immunohistochemistry. The mRNA and protein expression of SIK1 and SREBP-1c were detected using RT-PCR and Western blot.

RESULTSCompared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight index, and liver TG contents significantly increased (P < 0.01); liver steatosis was severe, the mRNA and protein expression of SIK1 obviously decreased (P < 0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver weight index significantly decreased, liver TG contents significantly decreased, the mRNA and protein expression of SIK1 obviously increased, while mRNA and protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological changes were also improved. All the indices were improved more in the ZQR group (all P < 0.05).

CONCLUSIONIn this experiment, we found that the expression of SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at mRNA and protein levels.

Animals ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Liver ; complications ; drug therapy ; metabolism ; Liver ; metabolism ; Male ; Protein-Serine-Threonine Kinases ; metabolism ; Rats ; Rats, Wistar ; Sterol Regulatory Element Binding Protein 1 ; metabolism

OBJECTIVE To investigate the clinical characteristics,risk factors and preventive measures for nosocomial pneumonia in patients with post-hepatitis liver cirrhosis.METHODS A prospective and retrospective study was carried out to investigate the clinical data of 495 patients with post-hepatitis liver cirrhosis in Department of Infectious Diseases during Jan 1,2005 to Dec 31,2007.RESULTS The incidence rate of the nosocomial pneumonia in post-hepatitis liver cirrhosis patients was 13.50 %.The death rate was 25.40 %,which was obviously higher than 6.8% of patients without no nosocomial infection(?2=23.77,P

Objective To investigate the protective effects of felodipine on mRNA levels of endothelial nitricoxide synthase (eNOS) and inducible nitricoxide synthase (iNOS) as well as the level of nitrogen monoxidum (NO) from human umbilical vein endothelial cells (HUVECs) injuryed by oxidized low density lipoprotein (ox-LDL). Methods Isolated HUVECs were divided into blank control group,ox-LDL injury group treated with ox-LDL of different concentrations (6,12.5 and 25 mg/L),and intervention group of felodipine (0.1,1.0 and 10 ?mol/L)+ox-LDL (25 mg/L). Then eNOS and iNOS expressions were measured by real time-polymerase chain reaction and the level of NO in the supernatants of the cultures was assayed by nitrate reductase method. Results The mRNA expressions of eNOS and iNOS in HUVECs and NO level in the supernatants during treatment with different ox-LDL concentrations were higher than those in control group. However,felodipine significantly down-regulated the expression of iNOS in HUVECs injured by ox-LDL and inceased NO generation. Conclusion Felodipine has protective effects on endothelial cells. The mechanism may be related to its lowering the mRNA expression of iNOS induced by low ox-LDL concentration and increasing NO production.

Objective To investigate the protective effect of felodipine on reactive oxygen species (ROS) generation,mRNA level of inflammatory factors such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1),in human umbilical vein endothelial cells (HUVECs) injured by oxidized low-density lipoprotein (ox-LDL) so as to explore felodipine's anti-atherosclerosis mechanism independent of its anti-hypertensive effect. Methods Isolated HUVECs were treated with ox-LDL at different concentrations (6,12.5 and 25 mg/L) for 24 hours so that the optimal concentration and time of ox-LDL treatment were selected. Then the cells were incubated with ox-LDL and treated with felodipine at different concentrations (0.1,1 and 10 ?mol/L). Intracellular ROS level was determined by flow cytometry (FCM). Expressions of inflammatory factors ICAM-1 and VCAM-1 were measured by real time-polymerase chain reaction (real time-PCR). Results ROS generation was increased in HUVECs after treatment with different concentrations (6,12.5 and 25 mg/L) of ox-LDL for 24 hours and there was a significant difference at 25 mg/L ox-LDL (P

Objective:To establish a rapid, sensitive and accurate HPLC-QTOF/MS determination method for the illegally added antihypertensive drugs in traditional Chinese medicines and healthy care products .Methods:An Agilent Eclipse plus C 18 column ( 50 mm ×2.1 mm,1.8 μm) was adopted with the mobile phase of 0.5%formic acid and acetonitrile with gradient elution .The flow rate was 0.2 ml· min-1 .The electrospray ionization source was applied and operated in a positive ion mode .Results:The detection limit of 18 antihypertensive drugs was within the range of 0.2-2.5 ng· ml-1 .Reserpine was found in one sample .Conclusion:The method is selective and sensitive , which can be used for the detection of 18 chemical medicines illegally added in antihypertensive traditional Chinese medicines and health care products .

″Herb-Pairs″, also known as pair drugs, refers to a prescription consisted of two relatively fixed traditional Chinese medicine, is the most basic, most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility. It is not a random combination of two herbs, nor is the simple accumulation of efficacy, but the simple and delicate experience of ancient Chinese medicine practitioners. As a bridge between single drug and prescriptions, it is the embodiment of the regular and dialectical connotation. Therefore, research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies. However, the interaction between herbs and herbs is an effect with a downside as well as benefits. The beneficial herb-herb interaction in Herb-Pairs include mutual promotion, mutual enhancement, mutual restraint between two drugs and counteract toxicity of another drug. And the harmful herb- herb interaction in Herb- Pairs includes mutual inhibition and antagonism. All of these interactions areby means of affecting the metabolism of components to play a therapeutic effect. Using the pharmacokinetic-pharmacodynamic (PK-PD) binding model, the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism, which can help elucidate the mechanism of drug action. Consequently, in this review, the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.

Objective To investigate the activation state of and expressions of surface co-stimulatory molecules on peripheral CD4+ T cells from patients with pemphigus and healthy human controls.Methods Ninety patients with pemphigus including 24 patients with first-onset pemphigus,51 with quiescent pemphigus and 15 with recurrent pemphigus,as well as 30 healthy human controls were enrolled in this study.Peripheral blood samples were obtained from these subjects followed by lymphocyte isolation.Flow cytometry was performed to detect the expressions of CD69,intercellular adhesion molecule-1 (ICAM-1),inducible co-stimulatory molecule (ICOS),CD40 ligand (CD40L) and OX40 on CD4+ T cells.Statistical analysis was done by Mann-Whitney test using Graphpad 5.0 software.Results The expression rate of CD69 on peripheral CD4+ T cells from the healthy human controls was significantly lower than that from patients with pemphigus,patients with first-onset pemphigus,patients with quiescent pemphigus,and patients with recurrent pemphigus ((1.26 ± 0.19)％ vs.(2.46 ± 0.19)％,(2.77 ± 0.40)％,(2.15 ± 0.25)％ and (2.36 ± 0.35)％,all P ＜ 0.05).The patients with pemphigus also showed a significant increase in the expression rates of ICAM-1,CD40L and OX40 compared with the healthy human controls ((55.88 ± 1.67)％ vs.(47.75 ± 2.52)％,P＜ 0.05; (2.23 ± 0.22)％ vs.(0.73 ± 0.07)％,P＜ 0.01; (2.55 ± 0.29)％vs.(0.62 ± 0.17)％,P ＜ 0.01).No significant differences were observed between patients with different stages of pemphigus in the expression rates of CD69,ICAM-1,CD40L or OX40 (all P ＞ 0.05).The percentage of ICOS-expressing CD4+ T cells was significantly up-regulated in only patients with first-onset pemphigus as compared to the healthy controls ((3.73 ± 0.60)％ vs.(2.39 ± 0.16)％,P ＜ 0.05).Conclusions The peripheral blood CD4+ T cells from patients with pemphigus are in a relatively active state with up-regulated surface expressions of many costimulatory molecules,suggesting that CD4+ T cells are involved in the initiation and progression of pemphigus by interacting with B cells through co-stimulatory molecules.

Objective To study the changes of antigen-specific T helper type 1 (Th1) cells and Th2 cells in patients with pemphigus vulgaris (PV) at different stages,so as to better understand the roles of autoreactive T cells in PV.Methods The DG3 (96-112) peptide was synthesized.Twenty-four patients with PV and 10 health checkup examinees were included in this study.Peripheral blood mononuclear cells (PBMCs) were obtained from the health checkup examinees and all the patients before treatment and seven patients about one month after treatment,and stimulated with the DG3 peptide of 10 mg/L for different durations.Then,enzyme-linked immunospot (ELISPOT) assay was performed to count the number of DG3-specific IFN-γ+ Th1 cells,IL-4+ Th2 cells and memory B cells.One-way analysis of variance (ANOVA) and t test were done to compare the number of cells between different groups,and Pearson correlation coefficient was used to evaluate the correlation among Th cells,memory B cells and anti-desmoglein 3 (Dsg3) antibody titers.Results In these patients,the male to female ratio was 1.67 ∶ 1,and the average age was (56.59 ± 14.66) years.Compared with the health check-up examinees,the patients with PV showed a higher absolute number of DG3-specific IFN-γ+ Th1 cells (420.18 ± 350.29 vs.145.12 ± 86.56,t =3.25,P ＜ 0.05),but a similar absolute number of specific IL-4+ Th2 cells (366.76 ± 192.44 vs.335.88 ± 164.96,P＞ 0.05) per 5 × 105 PBMCs.The percentage of DG3-specific IL-4+ Th2 cells in Th2 cells was 37.03％ ± 23.44％,and the percentage of IFN-γ+ Th1 cells was 23.62％ ± 16.77％ in peripheral blood of patients with PV.The number of DG3-specific IL-4+ Th2 cells per 5 × 105 PBMCs significantly decreased from 452.82 ± 199.29 before treatment to 241.68 ± 160.60 after treatment in seven patients (t =2.48,P ＜ 0.05).There was no significant correlation between specific Th cells,memory B cells and anti-Dsg3 antibody titers (all P ＞ 0.05).Conclusions The peptide DG3 (96-112) has pathogenic epitopes which could be recognized by specific Th cells of patients with PV.Both antigen-specific IFN-γ+ Th1 cells and IL-4+ Th2 cells play certain roles in the pathogenesis of pemphigns vulgaris,and IL-4+ Th2 cells appear to be more important.

Objective To study the efficacy of rituximab in the treatment of pemphigus vulgaris (PV) and its underlying mechanism. Methods A 38-year-old female with PV presented with refractory, painful oral ulcers and erosions. Since she was poorly responsive to prednisone 80 mg daily, intravenous ritu-ximab of 500 mg once a week was given for successive 3 weeks followed by 5 successive days of intra-venous gamma globulin at a dose of 400 mg/kg per day, and a total of two treatment sessions were conducted. ELISA was used to detect the serum titer of anti-Dsg3 antibodies and their IgG subtypes (IgG1 and IgG4) as well as serum level of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10). Results Three months after the end of two treatment sessions, the symptom was obviously improved, and lesions subsided; alter another 1 month, clinical symptom fully disappeared. During the 1-year follow-up, no lesions recurred. The anti-Dsg3 antibody titer was 253.33 U/mL before treatment, plateaued at 250 U/mL within 4 weeks after the initial infusion, decreased till 3 months after the withdrawal, and reached 26.06 U/mL 7 months after the withdrawal, and remained within normal range till the time of this writing. The serum titer of IgGl subclass of anti-Dsg3 antibodies dropped dramatically fight after the first infusion, but that of IgG4 subclass remained at a high level at early stage of medication, began to decline until 3 months after the with-drawal, and finally reached the normal range following clinical remission. Also, serum level of IFN-garnma and IL-10 correlated with the severity of PV. Conclusions Combined rituximab is effective for the control of PV, likely by eliminating Dsg3-specific antibodies, especially IgG4 subclass of them.