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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.
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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.
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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.
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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.
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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.
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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).
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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.
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【Objective】To evaluate the therapeutic effect and safety of Aikeqing Capsule(AC) combined with highly active antiretroviral therapy(HAART) for the treatment of acquired immunodeficiency syndrome(AIS).【Methods】Eighteen AIDS patients were equally randomized into two groups.Both of Groups A and B were given HAART,and group A received AC additionally.T lymphocyte subtypes were detected,scores of symptoms and signs and scores of symptoms and tongue feature as well as pulse condition were counted,body weight was examined and quality of life was evaluated with Karnovsky score before treatment and after treatment for 3 months and 6 months.Meanwhile,blood routine analysis,hepatic function,renal function and serum amylase content were examined to evaluate the safety of AC.【Results】After treatment,T lymphocytes subtypes were improved in the two groups(P0.05).In group A,symptoms and signs scores decreased(P
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【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.
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[Objective] To observe the effect of Baicalin on the expression of Toll-like receptors (TLRs) induced by chlamydia pneumoniae (CPN). [Methods] The endothelial cells of umbilical veins (ECV-304) was cultured in-vitro in 6-well culture plate (3 double-wells as a group). When a single layer formed, CPN or CPN + baicalin (0.48 g/L or 0.24 g/L) was added, serving as the model group and baicalin groups respectively. The wells without adding agents served as the normal group. After 5 days of culture, the intracellular growth of CPN in ECV-304 was examined by monoclonal antibody fluorescence labeling method and Giemsa stain, and the expression of TLR2 mRNA and TLR4 mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the model group. Protein expression of TLR2 on ECV-304 cell surface in the cultured supernatants was detected with flow cytometer. [Results] The intracellular growth of CPN can be found in ECV-304. The expression of TLR4 mRNA was undetectable, and high expression of TLR2 mRNA and TLR2 protein existed in ECV-304. Baicalin in high doses could lower the expression of TLR2 protein. [Conclusion] Baicalin has an inhibitory effect on the high expression of TLR2 protein in ECV-304 stimulated by CPN.
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Objective To study the effects of dihydroartemisinin and quinine on plasmodium falciparum gametocytes at early stage. Methods Eleven patients with falciparum malaria who had plasmodium falciparum gametocytes at early stage(PFGe) in bone marrow but no matured plasmodium falciparum gametocytes(PFGm) in bone marrow and peripheral blood were allocated to two groups.Group A(n=6) were administered orally with dihydroartemisinin at a total dosage of 480mg for 7 days and Group B(n=5) with quinine sulfate at a total dosage of 10?500 mg for 7 days.The number of gametocytes in bone marrow and peripheral blood was examined at regular time. Results PFGe in bone marrow disappeared in Group A on 10 th day after the first administration while existed in all the cases of Group B on 10 th day and still in 2 cases on 14 th day.The clearance time for peripheral PFGe was 4.8?0.9 days in Group A and 22.0?5.8 days in Group B. Conclusion Dihydroartemisinin can clear PFGe but quinine shows no this action.
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Objective To construct a DNA vaccine capable of expressing S gene of hepatitis B virus(HBV) and evaluate the expression of recombinant S gene in vitro and in vivo. Methods A cloned S X gene fragment was inserted into a eukaryote expression vector to construct a recombinant plasmid. The S gene was transcribed in vitro and expressed in a transfected cell line, and the efficiency of HBsAg in eliciting anti HBs was evaluated in mice. Results The expression of S gene was confirmed by Northern blotting, Western blotting, and ELISA(for both antigen and antibody detection). Conclusions The recombination and expression of S gene is achieved successfully in vitro.
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[Objective] To investigate the effect of ATA, a herbal medicine compound, for the treatment of the chronic infection of simian immunodeficiency virus ( SIV) in monkeys. [ Methods ] Eight Rhesus monkeys were infected with SIVmac251 to establish monkey models with chronic infection of SIV. After 18 months, the monkeys were randomized into model group and ATA group, administered with saline and ATA 2 g?kg-1?d-1 for 56 days respectively. The changes of signs were observed, plasma levels of T-lymphocyte subsets CD4+ and CD8+ were detected by flow cytometry and the lymph node biopsy were observed under light microscope before and after treatment. [Results] After treatment, the body weight increased and the incidence of infective diarrhea decreased in ATA group, the difference being insignificant. ATA had no obvious effect on white blood cells counting and the replication number of plasma SIV, but increased the plasma levels of T-lymphocyte subsets CD4+ and CD8+(P
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Objective To compare the effects of dual-wavelength spectrophotometry and HPLC on the content of trimethoprim(TMP)in Compound Dihydroartemisinin Tablets.Methods HPLC was performed in a column of C 18 with acetonitrile and 0.75% diethylamine(15∶85,adjusting pH to 2.5 by phosphoric acid)as the mobile phase and the detecting wavelength was at 271nm.The detecting wavelength was also at 271nm with reference wavelength at 366nm in dual-wavelength spectrophotomerty.Results Within 20.0～100.0 ?g/mL,TMP has a good linearity(r=0.999 94)by HPLC,and the average recovery was 100.9% with RSD being0.24%(n=5).By dual-wavelength spectrophotometry,a good linearity(r=0.999 95)of TMP was within 5.0～25.0 ?g/mL,and the average recovery was 100.0% with RSD being 0.45%(n=5).Conclusion Both dual-wavelength spectrophotometry and HPLC can be used to determine the content of TMP in Compound Dihydroartemisinin Tablets,but the former can detect the content of TMP directly without the disturbance of piperaquine phosphate and is simple,rapid and accurate.
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0.05),but was significant as compared with the blood syndrome(P0.05).Conclusion The syndromes of AIDS fever patients are complex,covering defense,Qi,nutrient,and blood phases as well as triple energizers,characterized as multiple fever types and different tongue and pulse conditions.During the syndrome differentiation of AIDS fever,the incidental and fundamental symptoms should be differentiated based on the synthetical analysis of four examinations.
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Object To explore the feasibility of breeding genetic modified (GM) medicine by expressing human cytokine in transgenic Chinese materia medica Methods Human interferon ? gene and RANTES gene available from the amplification in vitro were enzymatically excised, recoveried, and inserted into intermediate vectors The recombinants were identified by double enzyme digestion of EcoRⅠand HindⅢ The plasmids were extracted from Escherichia coli and introduced into A tumefaciens, and the transformants harboring binary vectors were screened by addition of antibiotics of kanamycin (Km) and rifampicin (Rif), and the explants of M charantia and P vulgaris were transformed by co cultivation of leaf disks with A tumefaciens strain Results RT PCR was applied to detect the transient expression of human interferon ? gene and RANTES gene in transformed medicinal herbal calli Conclusion The expression of recombinant human interferon ? gene and RANTES gene in transgenic M charantia and P vulgaris cells was firstly reported, which opens an alternative road to antivirus, especially anti AIDS virus, by using transgenic Chinese materia medica
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A study was carried out in south of Vietnam 15 Patients with Plasmodium falciparum gametocytes and asexual parasites were distributed into groups A, B and C. Artesunate was given orally at a total dose of 600 mg for 5 days in group A, 200 mg for 2 days in group B and intravenously at a total dose of 360 mg for 5 days in group C respectively. Gametocytes count was done before medication and daily after medication. Meanwhile, Anopheles dirus as a vector was employed to study the infectivity of gametocyte, The result showed that the mean gametocyte clearance time in three groups were respectively 15.4?5.0, 20.6?4.8 and 20.3?4.0 days. The mosquitoes were not infected from the blood in 2, 5 and 5 of 5 patients respectively on days 7, 14 and 21 in group A; 1 and 5 of 5 patients on day 14 and 21 in group B; 2 of 5 patients and 3 of 3 patients on days 14 and 21 in group C. It indicates that artesunate has remarkable effect on Plasmodium falciparum gametocytemia and its infectivity to mosquitoes.
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Objective To investgate the inhibitory effect of Phyllanthus Urinaria L compound on proliferation of hepatoma cell HePG2 in vitro and to explore its mechanism.Methods The influence of different concentrations of Phyllanthus Urinaria L compound at different time on HePG2 proliferation was compared by MTT colorimetric assay and cell growth curve assay.The cell apoptotic rate and morphological changes of HePG2 were observed by flow cytometry,fluorescence microscope and electron microscope.Results Phyllanthus Urinaria L compound can inhibit the proliferation of human hepatoma cell line HePG2.Within a certain limit of concentrations,the higher the concentration and the longer the acting time,the stronger the inhibition.Co-cultured with 500 ? g/mL Phyllanthus Urinaria L compound for 72 h,the inhibitory rate reached 93.58 % and IC50 was 240 ? g/mL.Phyllanthus Urinaria L compound at different concentrations had an certain effect on inducing cell apoptosis.Conclusion Phyllanthus Urinaria L compound can inhibit the proliferation of hepatoma cell,and its mechanism may be related with the induction of hepatoma cell HePG2 apoptosis.
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Objective To study the rule of distribution and evol vement of TCM syn dromes in HIV/AIDS patients. Methods Totally 177 HIV/AI DS patients were investigated with questionnaire in the epide miological study to collect the data of diagnosis, and the rou tine test of CD4+T lymphocyte count was carried out. Results The young and mid dle-aged females were the most involved group with an increasing incidence in G u angdong Province and with a strong relation of sex and infection route. The main symptoms of the 177 HIV/AIDS patients were fatigue, cough and loss of appetite, the secondary ones were night sweating, skin itching, headache, and hair loss, and the most common sign was skin rash. The leading TCM syndromes were qi and yi n deficiency and lung and kidney deficiency. The distribution of symptoms and si gns, syndromes and various indices was significantly different in gender, age an d infection route (P