Objective To investigate the effects of Aikeqing(AKQ),a compound of Chinese medicine,on drug-metabolizing activity and on the pharmacokinetic parameters of HIV-1 protease inhibitors lopinavir(LPV)and ritonavir(RTV)in Kaletra tablets.Methods Human liver microsomes were co-incubated with mixed probes and AKQ.HPLC-MS was employed to measure the content of probe.Half-inhibitory concentration(IC50)of AKQ on different subtypes of cytochrome P450 enzymes involved in drug metabolism of liver microsomes was calculated.The P450 subtype,whose activity was significantly inhibited by AKQ was then identified.HPLC-MS analytical method for simultaneous determination of LPV and RTV in rat plasma was established.SD rats were orally given AKQ or vehicle once a day for 7 consecutive days.After half an hour of the last gavage of AKQ,the rats were given Kaletra by intragastric administration.Then,the blood concentration of LPV and RTV were measured and the effect of AKQ on pharmacokinetic parameters of LPV and RTV were analyzed.Results The methanol extract of AKQ at the concentrations of 0～500 μg·mL-1 showed inhibitory effects on the metabolic activity of CYP2D6,CYP2C8、CYP2E1,CYP2C19,CYP1A2,CYP2B6,CYP2C9 and CYP3A4,with IC50 values of 7.7,75.3,144.0,99.5,43.5,104.5,49.3 and 204.9 μg·mL-1,respectively.An HPLC-MS/MS method was established for simultaneous quantification of LPV and RTV in blood samples.LPV and RTV showed linear relationships in the ranges of 30～10 000 ng·mL-1 and 3～1 000 ng·mL-1,respectively.The lowest limits of quantification were 30 ng·mL-1 and 3 ng·mL-1.Intra-day and inter-day precision were all less than 5%,and the accuracy of LPV and RTV was in the range of 96.3%～109%.The extraction recovery rates were not less than 88.7%,the matrix effects were 93.8%～105.0%,and the plasma samples were stable.Compared with Kaletra group,there was no significant changes in non-compartmental model parameters including AUC0-t,AUC0-∞,MRT0-t,t1/2z,tmax,Vz/F,Clz/F and Cmax of LPV in AKQ+Kaletra group(P＞0.05).But MRT0-∞ was found to be obviously affected by AKQ(P＜0.05).All pharmacokinetic parameters of RTV showed no significant change in AKQ+Kaletra group(P＞0.05).Conclusion Aikeqing exhibited varying degrees of inhibitory effects on 8 human drug-metabolizing cytochromes P450,especially CYP2D6.A human-equivalent dose of Aikeqing does not affect the pharmacokinetic parameters of lopinavir and ritonavir in rats.

At the 50th Anniversary of Project 523,we reviewed the course and progress made by the Artemisinin Anti-malaria Research Group of Guangzhou University of Chinese Medicine in the application of artemisinin for treating malaria.As one of the groups participating in the mission of Project 523,Artemisinin Anti-malaria Research Group of Guangzhou University of Chinese Medicine was in charge of the clinical trials in treating malaria with artemisinin and its derivatives of various preparation forms,dosages and treatment courses(years 1974-1989),developed the artemisinin-based combinations(ACTs) Artekin and Artequick for malaria treatment and performed their clinical trials(years 1984-2006).For the recent 10 years,the group has been devoted in the implementation of anti-malaria programme FEMSE (Fast Elimination of Malaria by Source Eradication) in south-east Asia and Africa.The scientific explorations and achievements of this research group have made great contribution in bringing artemisinins to the world and creating a simple,practical and cost-effective new method for rapid global malaria elimination.

Objective To compare the efficacy of highly active anti-retroviral treatment (HAART) with and with AZT. Methods Data of 235 HIV patients accepted from Oct. 2010 to Nov. 2013 who took AZT (133) or TDF (102) containing regimen as first-line HAART are analyzed retrospectively. CD4+ T cell counts acted as the base line after 12 months of HAART. Increase in CD4+ T cell count number after the HAART, virological failures and drug resistance were compared between the two groups. Results The two groups had comparable baseline CD4+T cell count, gender ratio, and HIV transmision mode; after 12 months of HARRT, no statistically differences were found between the two groups with regard to CD4 + T cell count and increase in CD4+ T cell count after the 12-month HAART (P > 0.05); AZT-containing group had more virological failure (3/0). Meanwhile AZT-containing group had one thymidine analog mutation (TAMs) which confers resistance to AZT (P > 0.05 for both). Conculsion The two HAARTs have same immunological effects; AZT-containing group exhibits 2.2% viralogial failure, but its direct relationship with AZT has not been confirmed.

Objective To screen the non-nucleoside compounds against HIV-1 reverse transcriptase by molecular modeling and bioactivity assay. Methods Surflex-Dock module of Tripos SYBYL software was used to simulate the binding pattern of 22 000 compounds in SPECS database with the active pocket of HIV-1 reverse transcriptase. Based on the simulation results, the interaction mode between the above compounds and the crystal structure of HIV-1 reverse transcriptase was analyzed. The compounds with higher docking scores and better binding pattern were determined by anti-HIV-1 ac tivities test in vitro. Results The virtual screening results showed that the docking conformation of 1- (4-fluorophenyl) -3- [2- (1H-indol-3-yl) ethyl] thiourea was similar to the embedded ligand in Rilpivirine crystal structure. 1- ( 4-fluorophenyl) -3- [ 2- ( 1H-indol-3-yl) ethyl] thiourea was held together with the key residue Lys101 in docking pocket of HIV-1 reverse transcriptase by hydrogen bonds, and hadπ-πstacking action together with the conservative residue Trp229 and the aromatic residue Tyr181 respectively. The bioassay in vitro results showed that when the proliferation rate of C8166 lymphocyte syncytium infected by HIV-1ⅢB arrived 50% ( EC50) , the concentration of 1- ( 4-fluorophenyl) -3- [ 2- ( 1H-indol-3-yl) ethyl] thiourea was 5.45μg/mL. Conclusion Molecule docking technology is an effective approach to reducing the screening of candidate compounds with micromolecular activity, and can be used to predict the interaction mode between the compound and the target receptor. In the study, active compound 1- (4-fluorophenyl) -3- [2- (1H-indol-3-yl) ethyl] thiourea has been screened out by molecule docking technology.

Objective To predict the disease progression risks of healthy rhesus ( normal) and rhesus infected with simian immunodeficiency virus ( SIV) in the stages of long-term nonprogressor ( LTNP) , normal progressor ( NP) , rapid progressor ( RP) by discriminant analysis. Methods Five-year observation was carried out in SIV infected rhesus model without any intervention. The SIV infected rhesus model at the stages of LTNP, NP, RP were selected, 10 in each group, and T lymphocyte subsets and serum parameters for spleen-deficiency syndrome and kidney-deficiency syndrome in SIV infected rhesus were compared with 5 healthy monkey having the same survival time. The influence factors of different types of disease progression were screened from T cell subsets and Chinese medical syndrome indexes, and then the discriminant equation was established to predict the risks. Results White blood cell ( WBC) count and lymphocyte ( LYM) ratio were enrolled into the discriminant equation before infection, and T4 level and Log10RNA of set point were enrolled into the discriminant equation in the platform period. The test results for the uniform rate of the established discriminant function showed that the total coincidence rate of theoretic distinguish to the actual data was 57.1% , 91.2%respectively before infection and in the platform period. Conclusion The pre-infection WBC count and LYM ratio can be used as a reference for the evaluation of different types of disease progresson, and Log10RNA and T4 level at platform phase can be used as the predicting factors of different types of disease progression risk prediction.

As the specific endangered medicinal plant in Xinjiang, resources and distribution of Ferula sinkiangen-sis are important for biodiversity conservation and sustainable development of Chinese medicine resources. The spa-tial distribution and resources of F. sinkiangensis were researched based on low altitude remote sensing and sample investigation. The results showed that the optimum working time for F. sinkiangensis monitoring by low altitude remote sensing was the nearby 5 hills, which covered about 0.88 km2. It was suggested that the fence area should be expanded for protection. According to the results of low altitude remote sensing, the amount of F. sinkiangensis in yellow (diameter exceeding 0.3 m) was about 3 191. However, the sample investigation on amount of F. sinkiangensis in yellow (diameter exceeding 0.3 m) was about 2 752. The error between them was 14%. The monitoring time and range for F. sinkiangensis by low altitude remote sensing were also ensured. It was concluded that low altitude re-mote sensing had the advantage of quickly receiving distribution situation of F. sinkiangensis, which can effectively evaluate dynamic changes of F. sinkiangensis in Xinjiang.

ObjectiveTo observe the virological and immunological items in peripheral blood of Chinese-origin Rhesus macaques infected with SIVmac251.The normal levels of WBC and CD4+T cell ratio for healthy Chinese-origin Rhesus macaques that suitable for simian AIDS modeling also investigated.MethodsThirty-six Chinese-origin Rhesus macaques were intravenously infected with SIVmac251.Blood samples were collected at 10 time points respectively include 1 day before SIV infection,every week within 1-8th week and then in tenth week post infection.Blood routine,peripheral blood T lymphocyte subsets,plasma viral load were tested.ResultsThe most significant changes of the tested items were appeared in 1 or 2 weeks post SIV infection,while the WBC counts didn't show marked changes in all the time points tested.WBC counts ranged from 4×106/ml to 10×106/ml and the CD4+T cells ratio high than 25％ are the suitable levels for simian AIDS modeling.ConclusionThis research provides necessary and beneficial informations to the usage of Chinese-origin Rhesus macaques in AIDS research.

To study the characteristics of traditional Chinese medicine (TCM) syndrome factors of patients from different areas of China with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).

Objective To investigate the clinical features, prognosis and risk factors of patients of acquired immunodeficiency syndrome (AIDS) complicated with cryptococcal meningitis (CM). Methods Totally 26 patients of AIDS with CM who were hospitalized in the No. 8th People's Hospital of Guangzhou were enrolled in this study. The clinical data including diagnosis,experimental and etiological test,treatments and prognosis from all the patients were analyzed retrospectively. The results of cerebrospinal fluid routine test and CD4+ T lymphocyte were compared with those of AIDS patients complicated with tuberculous meningitis. Results Among the 26 patients enrolled in the study, the positive rate of cerebrospinal fluid india ink smear or Crypotococcus neoforrnans euhure was 84.6%. The most common symptoms were fever, headache and meningeal irritation sign. The average CD4+ lymphocyte count was 17.83 × 106/L, which was statistically different from that of tuberculous meningitis patients. All the patients showed concomitant multiple organ infections. The mortality rate was as high as 42.3%. At the end of therapy, the cell counts in the eerebrospinal fluid were remarkably higher in the patients with unfavorable prognosis compared to the patients with good prognosis, which was statistically different. Conclusions CD4+ lymphocyte count is an important marker for differentiating CM from tuberculous meningitis in AIDS patients. The results of cerebrospinal fluid routine test can predict the prognosis.

【Objective】To establish a HBV-marker-producing nude mice model of human transplanted liver cancer(HTLC).【Methods】2.2.15 cells,a HePG2 cell line transfected with HBV genome,were injected subcutaneously into athymic BALB/c-nu mice aged 4～6 weeks.The growth of tumor was observed every week.After 36 days the nude mice were executed and HBV markers of HBsAg,HBeAg,and HBV-DNA as well as alpha-fetoprotein(AFP)in serum were detected.The pathological features of tumor tissues were examined under light microscope.【Results】The incidence of HTLC and the time of HTLC appearing were correlated with the number of transplanted 2.2.15 cells.Serum HBsAg,HBeAg,and HBV-DNA were positive in the HTLC transplanted mice,the serum content of AFP was(350?11.5) ?g/L,and pathological changes under light microscope were similar to human,indicating that the model has some similar histological characteristics of the human liver cancer infected by HBV.【Conclusion】The nude mice model of human transplanted liver cancer,which can produce HBV markers,is established successfully in this study.