Plasmodium falciparum is one of the main parasitic pathogens worldwide. Artemisinin derivatives are the first-line antimalarial drug. Recently, Plasmodium falciparum has been found to be tolerant to the treatment with artemisinin derivatives and its combination with piperaquine in several countries and regions. Scientists have found gene mutations associated with resistance of Plasmodium falciparum to artemisinin derivatives; however the mechanism of piperaquine resistance remains to be further studied. This review sums up the epidemic status and mechanism research of the resistance of Plasmodium falciparum to artemisinin derivatives and piperaquine.

Objective To build the cohort of drug resistance and analyze treatment efficiency of AIDS patients and situation of drug resistant mutations among HIV-1 infected individuals.Methods A cohort of 116 HIV-1 infected patients was built and their treatment progress were acquired once every 6 months.At the sanle time CD4+ T cell counts and HIV-1 viral load were measured and genotyping for drug resistance was determined by a home brew nested PCR.Results The CD4+ T cell count(470±251/ml)was higher than that before treatment in patients who were treated by AZT/DDI/NVP or D4T/DDL/NVP.The viral load was lower than that before treatmenL The drug resistant mutation frequency increased gradually along with treatment.The CD4+ T cell count was decreased and viral load was increased and the prevalence of drug resistant mutation was increased in the patients who changed regimens to AZT/3TC/NVP or D41/3TC/NVP.Only one primary mutation that was resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs)was detected in the naive patients.The cross-resistant mutation was detected in two patients after 6 months treatment. The intermediate resistance to lopinavir(LPV) was detected after 12 months treatment.The prevalence of high-grade resistances to NNRTIs was increased obviously,and the prevalence of multi-resistance and cross-resistance was detected in 5 patients after 36 months treatment.Conclusions The prevalence of primary mutation was rare in naive HIV-1 infected patients.The prevalence of drug resistant mutation was inereased gradually along with treatment.Ahhough few regimens were available,the treatment effect could last relatively long period of time if patients keep taking medicine stably.The regimens could be changed according to the results of drug resistant test.

This dissertation is to determine the biopotency of hemostat which processed in different places by establishing a bioassay method of Bletillae Rhizoma based on the thrombin time. Contrast test is the main methodology. Specifically, the reference substance of Bletillae Rhizoma is determined by comparing with the control substance of vitamin K1 using thrombin time, which is calibrated the Bletillae Rhizoma. The hemostatic biopotency is calculated by using the method of "parallel line assay method based on quantitative responses" (3.3) from different processed products. It indicates that there is a strong linear correlation between Bletillae Rhizoma and control drugs (Y = 66.332-23.913X, R2 = 0.995 3). The hemostatic biopotency of Bletillae Rhizoma from different processed products ranged between 821.93-1 187.53 U x g(-1) shown in the paper, and all of them can meet the requirements of the test. The methodology has an appropriate instrument precision (RSD 3.8%), intermediate precision (RSD 4.6%), repeatability (RSD 3.2%) and stability (RSD 3.7%). Therefore, it can be turned out that the methodology which established in the dissertation is good at determinating the hemostatic biopotency of Bletillae Rhizoma and it is reliable, simple and repeatable.
Animals ; Drugs, Chinese Herbal ; pharmacology ; standards ; Hemostatics ; pharmacology ; standards ; Orchidaceae ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Thrombin Time

Objective Toinvestigatetheimmunophenotypiccharacteristicsofacutemyeloidleukemia(AML) patients with NPM1 mutation. Methods The immunophenotype of 237 newly diagnosed AML patients were detected by flow cytometry. Real-time quantitative PCR was employed to detect the NPM1 mutation. The immunophenotype was then compared between the NPM1 mutated and wild type patients. Results The incidence of NPM1 mutation was 19.0 ％ (45/237) in all AML patients.The NPM1 mutated patients had lower expression of CD34,CD117,HLA-DR,CD15 and CD19 than the wild type patients(all P＜0.05).For AML patients with normal karyotype,the incidence of NPM1 mutation was 37.7 ％ (40/106),and the NPM1 mutated patients had lower expression of CD34,HLA-DR,CD15 and CD7 than the wild type patients(all P＜0.05).The NPM1 mutated patients with normal karyotype had lower expression of CD34 HLA-DR and CD7 in M1 subtype(all P ＜ 0.05); lower expression of HLA-DR and higher expression of CD9 in M2 subtype (all P ＜ 0.05) ; and lower expression of CD117 in M5 subtype compared with wild type patients (P ＜0.05). Conclusion The immunophenotypic characteristics of AML patients are changed by NPM1 mutation. The changes of immunophenotype varied in different FAB subtypes.

In vivo tumor imaging technique method based on bioluminescence principle was established to evaluate the anti-tumor effect of paclitaxel mixed micelle (PMM). MDA-MB-231 tumor cells with luciferase reporter vectors were firstly implanted into nude mice, and subsequently the luciferase substrate was regularly injected during intraperitoneal administration of PMM. Then the tumor size, growth and the intensity of light signals were monitored with in vivo imaging technique. The method of luciferase tumor in vivo imaging could be real-time, reliable and exact in labeling and reflecting the growth of tumors, and the observed results were consistent with that by conventional method, so it would be a feasible approach to study anti-tumor effect of drugs. The anti-tumor effect of paclitaxel mixed micelle was observed by this method, and the results showed that this formulation could inhibit growth of tumor, and the anti-tumor rate of it was about 85%.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Cell Line, Tumor ; Female ; Humans ; Luminescent Measurements ; Male ; Melanoma, Experimental ; drug therapy ; pathology ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Micelles ; Neoplasm Transplantation ; Paclitaxel ; administration & dosage ; pharmacology ; therapeutic use ; Particle Size ; Tumor Burden ; drug effects

OBJECTIVETo prepare monoclonal antibody (mAb) against prM epitope.

METHODSThe gene encoding prM was isolated using RT-PCR from brain of JEV infected mouse and cloned into prokaryotic expression vector pET-32a. Recombinant plasmid was transformed into E.coli BL21/DE3/LysS, then the transformed cells were expressed with the induction of IPTG. The expression and purification of the prM protein was analyzed by SDS-PAGE. The BALB/c mice were immunized with purified prM protein. Hybridoma cell lines secreting monoclonal antibodies against prM were established after cell fusion of mouse splenic cell and P3-X63-Ag8.653 cells. The specificity of mAb was identified by ELISA, Western Blot and Immunohistochemistry assay.

RESULTSmAb against prM epitope of JEV was prepared successfully.

CONCLUSIONThe obtained prM specific mAb was valuable for the prevention and dignosis of Japanese encephalitis.

Animals ; Antibodies, Monoclonal ; analysis ; immunology ; isolation & purification ; Antibody Specificity ; BALB 3T3 Cells ; Cell Line ; Cloning, Molecular ; Electrophoresis, Polyacrylamide Gel ; Encephalitis Virus, Japanese ; genetics ; immunology ; Epitopes ; immunology ; Escherichia coli ; genetics ; Mice ; Plasmids ; genetics ; metabolism ; Prokaryotic Cells ; metabolism ; Sequence Analysis, DNA ; Viral Proteins ; biosynthesis ; genetics ; immunology ; isolation & purification

OBJECTIVETo compare and evaluate the cost and effectiveness of endoscopic variceal ligation (EVL) at emergency plus octreotide versus octreotide alone in the treatment of acute esophageal variceal bleeding in cirrhotic patients.

METHODSSeventy-eight patients with active variceal bleeding under emergency endoscope, were assigned to two groups receiving either combined therapy of EVL at emergency and octreotide ('EVL' group) or a continuous infusion of octreotide alone ('octreotide' group). Both efficacy and cost-effectiveness were observed.

RESULTSThere were no significant differences between the two groups in patients' characteristics, supporting treatment or general treatment. In group EVL, there appeared a significantly higher rate in controlling bleeding and lower complication rate than that of octreotide group(94.4% vs.78.6%, P = 0.045 and 19.4% vs. 42.9%, P = 0.027, respectively). Early rebleeding and mortality rate were also lower in group EVL, but with no significant differences between them (2.9% vs. 7.7%, P = 0.358 and 5.6% vs. 14.3%, P = 0.205, respectively). The combined therapy had a significantly shorter time of hemostasis, less administration of octreoid, fewer units of blood transfusion and shorter hospital stay (P < 0.001). The median costs of the combined therapy and octreotide alone were RMB 9046.5 Yuan and 13 743.6 Yuan,respectively (P = 0.045). The cost-effective ratio of group EVL seemed superior to that of octreoid group.

CONCLUSIONThe therapeutic scheme of emergency EVL plus octreotide was a more cost-effective one for controlling acute esophageal variceal bleeding.

Combined Modality Therapy ; Cost-Benefit Analysis ; Emergency Medical Services ; Endoscopy, Gastrointestinal ; Esophageal and Gastric Varices ; complications ; Gastrointestinal Hemorrhage ; etiology ; therapy ; Humans ; Ligation ; economics ; Liver Cirrhosis ; complications ; Octreotide ; economics ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the effect of vitamin D on the expression of chemokine regulated on activation, normal T cells expressed and secreted (RANTES) in the lung tissue of asthmatic rats, and the role of vitamin D in the control of asthmatic airway inflammation and the synergistic action of hormones.

METHODSForty female Wistar rats were randomly and equally divided into normal control, asthma, vitamin D intervention, budesonide intervention, and budesonide+vitamin D intervention groups. Hematoxylin and eosin staining was used to observe pathological changes in the lung tissue. Immunohistochemistry was used to measure the protein expression of RANTES in lung tissue. Enzyme-linked immunosorbent assay was used to measure the level of RANTES in bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was used to measure the mRNA expression of RANTES.

RESULTSThe asthma group showed the most significant pathological changes in the lung tissue, including inflammatory cell infiltration, bronchial stenosis and distortion and smooth muscle rupture, while the intervention groups showed fewer pathological changes. Of the intervention groups, the budesonide intervention group showed fewer pathological changes than the vitamin D intervention group, and the budesonide+vitamin D intervention group showed the mildest pathological changes, which were similar to those observed in the normal control group. Protein expression of RANTES in the lung tissue and BALF was significantly higher in the asthma group than in the normal control group (P<0.05), while it was lower in the intervention groups than in the asthma group, exhibiting significant differences between each intervention group and the asthma group (P<0.05) (except the difference in protein expression of RANTES in BALF between the vitamin D intervention and asthma groups). The budesonide+vitamin D intervention group showed less protein expression of RANTES in the lung tissue and BALF than both the budesonide intervention and vitamin D intervention groups (P<0.05). The mRNA expression of RANTES was significantly higher in the asthma group than in the normal control group (P<0.05), while it was significantly lower in three intervention groups than in the asthma group (P<0.05), however no significant difference was found between the intervention groups in this regard. The budesonide+vitamin D intervention group showed the lowest level of RANTES mRNA, with no significant difference from the normal control group.

CONCLUSIONSThe mRNA and protein expression of RANTES in BALF and lung tissue increases significantly in asthmatic rats. Vitamin D intervention can decrease the expression of RANTES, suggesting that vitamin D can reduce airway inflammation by regulating the expression of RANTES. Vitamin D can be used together with budesonide to further decrease the mRNA and protein expression of RANTES.

Animals ; Asthma ; drug therapy ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Budesonide ; therapeutic use ; Chemokine CCL5 ; analysis ; genetics ; Enzyme-Linked Immunosorbent Assay ; Female ; Immunohistochemistry ; Lung ; metabolism ; pathology ; Rats ; Rats, Wistar ; Vitamin D ; pharmacology

OBJECTIVETo observe the changes of systemic and pulmonary hemodynamics and the plasma levels of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) and investigate their association in patients with hepatopulmonary syndrome (HPS).

METHODSTwenty-six patients with HPS undergoing orthotopic liver transplantation (OLT) were enrolled in this study with 20 patients without hypoxemia as the control group. Blood samples were taken one day before OLT to measure the plasma levels of iNOS and ET-1 using fluorescence quantitative polymerase chain reaction (FQ-PCR) and radioimmunoassay, respectively, with 10 healthy volunteers serving as the healthy control group. Before the operation for OLT, the parameters of systemic and pulmonary hemodynamics were monitored after anesthesia induction.

RESULTSThe systemic and pulmonary hemodynamics in patients without hypoxemia was characterized by high cardiac output and low resistance, and by comparison, the patients with HPS showed even higher cardiac output and lower mean pulmonary artery pressure, pulmonary artery wedge pressure, systemic vascular resistance and pulmonary vascular resistance. The two patient groups had comparable plasma iNOS and ET-1 levels, which were both higher than those in the healthy control group.

CONCLUSIONThe hemodynamics in patients with end-stage liver disease exhibit a pattern of high cardiac output and low resistance, which is more obvious in HPS patients possibly in association with elevated plasma levels of iNOS and ET-1.

Adult ; Aged ; Case-Control Studies ; Endothelin-1 ; blood ; Female ; Hemodynamics ; physiology ; Hepatopulmonary Syndrome ; blood ; physiopathology ; Humans ; Male ; Middle Aged ; Nitric Oxide Synthase Type II ; blood ; Pulmonary Circulation ; physiology ; Young Adult

Objective To evaluate the clinical efficacy and safety of adefovir and entecavir in the treatment of chronic hepatitis B ( CHB ) . Methods Eighty -six patients with CHB were recruited from 2012 to 2013 in our hospital and randomly divided into adefovir group ( n=41 ) and entecavir group ( n=45 ) .Patients in the adefovir group and ente-cavir group were given adefovir 0.5 mg? d-1 , po and entecavir 10 mg? d-1 , po, respectively.The treatment lasted for 12 months.The he-patitis B virus( HBV) DNA, HBV negative rate and adverse drug reac-tions in two groups were compared before and after treatment.Results After 12 months treatment, the HBV DNA were significantly decreased in both groups [ ( 4.21 ±0.71 ) vs ( 4.01 ±0.68 ) log10 copies? mL-1 ] with statistical difference ( P <0.05 ) , but no statistical difference in HBV negative rate and ALT normal rate was found between the two groups ( P>0.05 ) .Conclusion Significant clinical efficacy of both adefovir and entecavir was found in the treatment of chronic hepatitis B, with less adverse drug reactions.