Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.
Cholesterol Ester Transfer Proteins ; antagonists & inhibitors ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; Molecular Docking Simulation

OBJECTIVETo obtain the monoclonal antibody against hexon protein of human adenovirus.

METHODSBALB/c mice were immunized with purified recombinant hexon protein, and the spleen cells of the mice were isolated and fused with myloma cells. Four hybridoma cell strains were screened by indirect ELISA and cultured, and the sensitivity, specificity and virus neutralizing activity were analyzed with ELISA, Western blotting and neutralizing test.

RESULTSThe mouse ascites produced by these hybridoma cells contained specific monoclonal antibodies against hexon protein of human adenovirus as identified by ELISA and Western blot, and the antibody generated by 4C6 strain showed human adenovirus type 3-neutralizing activity.

CONCLUSIONThe monoclonal antibodies against hexon protein with high specificity have been successfully obtained, and these antibodies can be useful in developing assays for early diagnosis of HAdV3 infection and also in study of therapeutic drugs of the infection.

Adenoviruses, Human ; chemistry ; immunology ; Animals ; Antibodies, Monoclonal ; biosynthesis ; immunology ; Antibodies, Viral ; biosynthesis ; immunology ; Blotting, Western ; Capsid Proteins ; biosynthesis ; genetics ; immunology ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; Humans ; Hybridomas ; secretion ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; biosynthesis ; immunology

We aimed to provide scientific evidence for the effective control of the epidemic and to investigate the sources of infection and possible ways of transmission.Epidemiological investigation was carried out to explore the source of infection by using the case-control study.Results showed that the outbreak of the epidemic was hemorrhagic fever,the onset of 40 cases was from August 21 to September 4,accounting for 73.68 ％ of the case number.Cases were cluster in Weizhuang Town,Feinan Town and Longkang Town,accounting for 60.00％ of the case number.The cases who aged from 40 to 79 years accounted for 85.00％.The cases with medium and high fever,tiredness,chills,muscle pain,gastrocnemius and headache accounted for 85.00％,95.00％,90.00％,75.00％,62.50％ and 40.00％,respectively.The 97.50％ cases had exposure history of suspected contaminated water.Case-control study result showed that hands and feet had the wound in 15 days before the onset (x2=15.74,P ＜0.01),and farming work in 15 days before the onset (x2 =11.08,P ＜0.01) were the risk factors of leptospirosis infection.There are the bacteria change and the trend from south to north along the Huaihe River Basin.Strengthen the monitoring work in high-risk areas was the effective measurement to reduce the incidence of leptospirosis.

OBJECTIVETo evaluate the incidence of precore mutation in HBeAg negative HBV infected patients and the therapeutic effect of the immune therapy (levamisole + HBV vaccine + dipyridamole) on patients chronically infected by HBV with precore mutation.

METHODSThe precore region of HBV from the HBeAg (-) chronic hepatitis patients was sequenced and the patients suffered from HBV with precore mutation were treated with immune therapy.

RESULTSThe precore mutation rate was 10/12. The therapeutic effect of the immune therapy on the precore mutation patients (5/7) was better than that on the HBsAg(+), HBeAg(+) patients (2/11), P less than 0.05.

CONCLUSIONThe precore mutation rate was quite high in the HBsAg(+), HBeAg(-) patients we studied. The immune-therapy has some therapeutic effects on the patients with precore mutation. But the number of cases was too small, further study is needed.

Adolescent ; Adult ; Child ; Combined Modality Therapy ; DNA, Viral ; blood ; Dipyridamole ; therapeutic use ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; genetics ; isolation & purification ; Hepatitis B, Chronic ; therapy ; virology ; Humans ; Immunotherapy ; Lamivudine ; therapeutic use ; Levamisole ; therapeutic use ; Middle Aged ; Mutation

OBJECTIVETo investigate the therapeutic effect of Lugua polypeptide on active rheumatoid arthritis (RA).

METHODSFifty patients with active RA were selected for the study and were randomly divided into study group and control group. Patients in study group were treated with Lugua polypeptide intravenously at a dose of 16 mg per day and those in control group were given Celecoxib 200 mg twice a day for successive 2 weeks. Two groups were given the same basic treatment. Tenderness and swelling of joints, morning stiffness, erythrocyte sedimentation rate, C-reactive protein,rheumatoid factor and so on were recorded before and after treatment.

RESULTSThe above index on joints in study group was significantly improved compared with that in control group and the level before treament. No apparent side effects were observed.

CONCLUSIONLugua polypeptide is effective and safe on active RA. It is a promising agent in the treatment of RA.

Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; Arthritis, Rheumatoid ; drug therapy ; Female ; Humans ; Injections ; Male ; Middle Aged ; Peptides ; administration & dosage

This study was aimed to investigate the prophylactic effect of Toll like receptor (TLR)5 agonist flagellin on acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its possible mechanism. The animal model with allo-HSCT aGVHD was established by using purebred mice (male mouse C57BL/6 as donor, female mouse BALB/c as recipient) with complete-unidentical major histocompatibility antigen. The recipient mice were randomly divided into 3 groups: group 1 in which mice were injected with high purity (95%) flagellin before and after allo-HSCT respectively, group 2 in which mice received allo-HSCT without injection of flagellin, group 3 in which mice were radiated alone. The aGVHD features of mice in group 1 and 2 were observed and compared. The results showed that the typical symptoms of aGVHD appeared in transplanted mice. The death peak of mice in group 2 appeared at day 4-5 after transplantation. The aGVHD symptoms were obviously alleviated and the mean survival time was prolonged significantly in mice group 1 as compared with mice in group 2 (P < 0.05). The comparison of WBC count in peripheral blood of mice in 3 groups before transplantation showed no significant difference (P > 0.05), while WBC count of mice in group 1 and 2 showed the significant difference at days 14 and 21 after transplantation (P < 0.05). The pathological appearances of aGVHD in mice of group 1 were obviously reduced as compared with mice in group 2. The flow cytometric detection of Treg cell/CD4(+) T cell levels at different time before and after transplantation demonstrated that the Treg cell level in mice of group 1 at weeks 2-4 after transplantation significantly increased as compared with mice in group 2 (P < 0.05). It is concluded that flagellin can effectively prevent the aGVHD occurrence after allo-HSCT, reduce the symptoms and pathological changes of aGVHD, obviously prolong mean survival time of mice in group 1. The mechanism of flagellin effect may be associated to increase of Treg cell level in mice after allo-HSCT.
Animals ; Female ; Flagellin ; therapeutic use ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; Toll-Like Receptor 6 ; agonists ; Transplantation, Homologous

BACKGROUNDBiliary cast syndrome (BCS) was a postoperative complication of orthotopic liver transplantation (OLT), and the reason for BSC was considered to relate with ischemic type biliary lesions. This study aimed to evaluate the relationship between BCS following OLT and the hepatic artery resistance index (HARI), and to observe pathological changes and morphology of biliary casts.

METHODSTotally, 18 patients were diagnosed with BCS by cholangiography following OLT using choledochoscope or endoscopic retrograde cholangiopancreatography. In addition, 36 patients who did not present with BCS in the corresponding period had detectable postoperative HARI on weeks 1, 2, 3 shown by color Doppler flow imaging. The compositions of biliary casts were analyzed by pathological examination and scanning electron microscopy.

RESULTSHARI values of the BCS group were significantly decreased as compared with the non-BCS group on postoperative weeks 2 and 3 (P < 0.05). Odds ratio (OR) analysis of HARI 1, HARI 2, HARI 3 following the operation was >1 (OR = 1.300; 1.223; and 1.889, respectively). The OR of HARI 3 was statistically significant (OR = 1.889; 95% confidence interval = 1.166-7.490; P = 0.024). The compositions of biliary casts were different when bile duct stones were present. Furthermore, vascular epithelial cells were found by pathological examination in biliary casts.

CONCLUSIONSHARI may possibly serve as an independent risk factor and early predictive factor of BCS. Components and formation of biliary casts and bile duct stones are different.

Aged ; Biliary Tract Diseases ; pathology ; Cholangiopancreatography, Endoscopic Retrograde ; methods ; Female ; Hepatic Artery ; surgery ; Humans ; Liver Transplantation ; adverse effects ; Male ; Middle Aged

OBJECTIVETo explore the treatment outcomes of obese type 2 diabetes mellitus (T2DM) after laparoscopic gastric bypass.

METHODSThe clinical data of 18 patients with obese T2DM who underwent laparoscopic Roux-en-Y gastric bypass in Beijing Shijitan Hospital between March 2009 and February 2011 were retrospectively analyzed. The clinical parameters included preoperative and postoperative blood glucose, blood lipid, nutrition status and weight lose.

RESULTSEighteen patients included 8 men and 10 women. The range of age was 27-62 years (mean, 42.4±10.7 years). The range of BMI was 28.7-57.4 kg/m(2)(mean, 34.9±6.9 kg/m(2)). All the patients underwent laparoscopic Roux-en-Y gastric bypass, and no mortality, complication or conversion to open operation occurred. At 3 months after operation, there were significant changes in OGTT, BMI, HbA1c, Homa-IR and Homa-β(all P<0.05). Fourteen patients(77.8%) showed clinical complete remission, and the overall effective rate was 100%(18/18). The level of blood lipid decreased significantly (P<0.05), and the change of nutritional status was not statistically significant(P>0.05).

CONCLUSIONGastric bypass is an effective treatment for obese type 2 diabetes mellitus.

Adult ; Diabetes Mellitus, Type 2 ; complications ; surgery ; Female ; Gastric Bypass ; methods ; Humans ; Laparoscopy ; Male ; Middle Aged ; Obesity ; complications ; surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo observe the dynamic changes of CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood of patients with sepsis and discuss the clinical significance.

METHODSSixty-four patients admitted in the Emergency Center and Emergency Intensive Care Unit of the Second Hospital of Wenzhou Medical University between August, 2007 and July, 2009 were enrolled in this study. CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood were detected by flow cytometry on days 1, 7 and 14 after admission, and the results were compared between the patients with improvement of the condition and those without improvement, with 20 healthy subjects as the control group.

RESULTSOn day 1 after admission, CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio were obviously lower in the 2 groups of patients with sepsis than in the control group (P<0.05), but no significant difference was found in CD8+ T lymphocytes. The sepsis patients with clinical improvement showed significant higher CD3+ and CD4+ T lymphocyte percentages and CD4+/CD8+ T cell ratio than those without improvement on day 1. In the patients with clinical improvement, CD3+ and CD4+T lymphocytes and CD4+/CD8+ T cell ratio increased gradually with time and till day 14, they were comparable with the control levels; in the patients without improvement, CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio showed no obvious alterations in the course of observation.

CONCLUSIONImmune imbalance occurs in patients with sepsis represented by lowered CD3+ and CD4+T lymphocyte percentages and CD4+/CD8+ T cell ratio in relation to the severity of the condition. CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T cell ratio can be used as the indicators for assessing the severity of sepsis.

Adult ; Aged ; Aged, 80 and over ; CD4-CD8 Ratio ; Case-Control Studies ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Sepsis ; blood ; immunology ; T-Lymphocyte Subsets ; cytology

Objective To provide data for the control and prevention of hepatitis B and HBV surface antigen(HBsAg)status among the appliances and practitioners working in the public service places.Methods 63 beauty parlors,barber shops and bathing centers selected under stratified randomization sampling method and 682 workers were investigated through questionnaire.HBsAg from the appliances of the public service places and employee was detected by RIA.Results Two main sanitizing modes that including alcohol cleaning(34.60%)and ultraviolet light disinfection(30.79%)were used.The rates of testing on HBsAg among the appliances were 2.13% at the public service places,and were 0.63%,2.67% and 3.70% in large-.medium-and small-sized appliances respectively.The rate of testing on HBsAg on large-,medium-and small-sized appliances were statistically different(χ2=6.68,P＜0.05).The positive rates of HBsAg on the appliances of beauty parlors,barbering shops and footbath inns were 2.97%,0.61% and 3.42% respectively.People working in different service sites had different rates of HBsAg:those who worked at the‘acne needle'and the forceps were 5.13% and 4.17%.The positive rate of HBsAg among the workers in the public service places was 7.13%.The rates of HBsAg among the workers in large-,medium-and small-sized public service places were 7.34%,8.33% and 2.94% respectively.The rates of HBsAg among the workers in beauty parlors,barbering shops,footbath inns and bathing centers were 9.01%,6.37%,4.35% and 7.29% respectively.HBsAg positive rates were different among the workers working at different service sites:13.33% at tattoo business.12.68% in pedicures workers and 8.03% in massagists.Conclusion It is important to improve the sanitizing management of the appliances used in the public service places and to improve the knowledge,attitude,as well as practice of vaccination on hepatitis B among those populations.