Objective:To investigate the drug-resistant mutations of human immunodeficiency virus-1 (HIV-1) in patients who received highly active antiretroviral therapy (HAART) from 2014 to 2018.Methods:A total of 880 patients with HIV-1 infection who had been treated with HAART for more than six months in Chongqing Infectious Disease Medical Center from May 2014 to December 2018 were enrolled. Plasma samples were collected, and one-step reverse transcription-polymerase chain reaction (PCR) and nested PCR were taken to amplify protease and reverse transcriptase regions of HIV-1 pol gene region. The obtained amplified nucleotide sequences were compared with the drug resistance database for antiviral drug resistance analysis. Viral genotyping tool software was used to analyze HIV-1 subtype distribution. The categorical variables were compared using chi-square test. Results:Among 880 patients, the plasma HIV-1 viral load was (4.12±0.63) lg copies/mL, the CD4 + T lymphocyte count was (251±124)/μL, and the median duration of antiviral therapy was 26 months. In the subtypes analysis, the circulating recombinant form (CRF) 01-AE subtype was the largest proportion of HIV-1 subtypes, accounting for 38.9%(342/880), and the CRF07-BC subtype accounted for 28.5%(251/880), B+ C subtypes accounted for 16.2%(143/880). Drug-resistant mutations were detected in 534 patients, with a total drug resistance rate of 60.7%. The drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) were 51.0%(449/880), 58.6%(516/880) and 1.7%(15/880), respectively. The drug resistances to lamivudine, emtricitabine, efavirenz, and nevirapine were serious, and the medium/high resistance rates were 46.8%(412/880), 46.8%(412/880), 51.3%(451/880), and 53.6%(472/880), respectively, while those to zidomidudine (6.0%, 53/880), etravirin (9.0%, 451/880) and PI were not serious. M184IV (47.3%), K65R (22.2%) and K70RE (12.6%) were the most frequent mutations for NRTI. K103NS (25.1%), V106A (19.7%) and V179DE (14.4%) were the most frequent mutations for NNRTI. The most common drug-resistant mutations for PI were L10FIV (7.4%) and A71IVT (6.5%). The drug resistance rate of CRF01-AE subtype (69.3%, 237/342) was higher than those of CRF07-BC subtype (49.8%, 125/251) and B+ C subtype (51.0%, 73/143), the differences were statistically significant ( χ2=22.6 and 14.6, respectively, both P<0.05). Conclusions:The incidence of drug resistance is high among HIV-1 infected patients after six-month HAART treatment in Chongqing City. The drug resistance to NNRTI is the most common, followed by NRTI, while PI is less resistant. Drug resistance is the main reason for the virological breakthrough in HIV-1 infected patients.

Objective To establish HPLC assaying methods for the determination of albiflorin in the Jinsha-Paishi infusion, and to determine the content of albiflorin of different batches ofJinsha-Paishiinfusion. Methods The chromatographic conditions were with the column of C18 (250 mm × 4.6 mm, 5μm), mobile phase of methyl alcohol-aqua (25:75,V/V), flow rate of 1.0 ml/min, and determined at wave length of 230 nm in room temperature. A total of 3 different batches of albiflorin were determined.Results In the range of 2.5-200μg, the distribution of paeoniflorin was linear (r=0.999 8), and theRSD of precision, stability and repeatability were less than 2%. The average recovery was 98.05%, andRSD was 1.65%. The contents of albiflorin in each batch were 0.080, 0.083, 0.077 mg/g.Conclusion The assaying method of HPLC is convenient, accurate and reliable to determinate the content of albiflrin in theJinsha-Paishi infusion. And the results showed that there was no difference of content of albiflorin among the different batches ofJinsha-Paishi infusion.

Objective To observe the targeting effect of curcumin gelatin microsphere in rats in vivo. Methods Injections of curcumin gelatin microsphere and curcumin were injected via tail vein, respectively. HPLC was used to determine the content of curcumin in different organs. The pharmacokinetic parameters were calculated on the basis of compartment models by using DAS 2. 0 program. Targeting efficiency was used to evaluate tissue distribution of curcumin. Results Targeting efficiency of curcumin gelatin microsphere in heart, liver, spleen, lung and kidney was 0. 875, 0. 121, 1. 182, 5. 834 and 0. 896, respectively. Conclusion Curcumine gelatin microspheres can improve lung-targeting efficiency, and benefit for study on lung targeting therapeutic effect.

Objective To investigate the effects of intestinal ischemia reperfusion (IIR) on the progression of inflammatory reaction in hemorrhagic necrosis pancreatitis (HNP).Methods Eighty rats were randomly divided into sham operation (SO) group,acute edematous pancreatitis (AEP) group,AEP + IIR group and HNP group according to the random number table.Erythrocyte velocity (EV),functional capillary density (FCD) and leukocyte adherence (LA) were observed at 0,1,2,3 and 6 hours after the models were completed.The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected.All data were analyzed by using the analysis of variance or the t test.Results The level of EV in the AEP group significantly decreased at 1 hour,and got increased at 3 hours,while the level of EV in the AEP group was still significantly lower than that in the SO group ( t =9.60,P ＜ 0.05 ).The levels of EV in the AEP + IIR group and HNP group constantly decreased,and increased at 6 hours,but were continually lower than that in the AEP group ( t =6.03,6.12,P ＜0.05 ).The level of FCD in the AEP group was significantly lower than that in the SO group at 3 hours ( t =8.20,P＜0.05).The levels of FCD in the AEP + IIR group and HNP group were significantly lower than that in the AEP group at 3 hours (t =35.60,23.80,P ＜ 0.05 ).Compared with AEP group,the level of LA in the AEP group was significantly increased at 1 hour ( t =75.00,P ＜ 0.05 ) and reached peak at 3 hours.The levels of LA in the AEP + IIR group and HNP group were significantly higher than that in the AEP group at 1,2,3,6 hours (t =23.00,29.50,53.00,38.70,23.10,48.20,39.20,47.50,P＜0.05).Compared with SO group,the level of TNF-α in the AEP group significantly increased since l hour (t =77.00,P ＜ 0.05),and began to decrease at 3 hours; the levels of TNF-α in the AEP +IIR group and HNP group at 2 hours were significantly higher than that in the AEP group (t =23.50,18.10,P＜0.05).The levels of IL-6 in the AEP group at 1,2,3,6 hours were significantly higher than those in the SO group ( t =93.50,146.00,243.60,209.20,P ＜ 0.05 ).The levels of IL-6 in the AEP + IIR group and HNP group at 1 hour were not significantly different from that in the AEP group ( t =2.30,2.03,P ＞ 0.05),while the levels of IL-6 in the AEP + IIR group and HNP group at 2 hours were significantly higher than that in the AEP group (t =35.63,29.80,P ＜ 0.05 ).Conclusion IIR may enhance the inflammatory reaction of AEP and IIR might be one of the factors to exaggerate the inflammatory reaction of HNP.

Objective To explore the therapeutic effect of immune regulating nutrition on severe acute pancreatitis (SAP). Methods The clinical data of 80 patients with SAP who were admitted to the Union Hospital of Huazhong University of Science and Technology from February 2008 to October 2009 were prospectively analyzed. The 80 patients were equally divided into conventional nutrition (CN) group and immune regulating nutrition (IRN) group. Patients in the CN group received CN support, while patients in the IRN group were supplemented with ω-3 polyunsaturated fatty acid (ω-3 PUFA ) and glutamine at the basis of CN support.APACHE Ⅱ scores were evaluated at day 1, 4, 7, 10, 14 in the course of treatment. The differences in the incidence of pulmonary and abdominal infection, sepsis, and other clinical parameters including operation intervention, mortality, length of ICU and hospital stay between the two groups were compared. All data were analyzed using the t test and chi-square test. Results The APACHE Ⅱ scores of patients in the IRN group were 15.3 ± 1.8 and 9.0 ± 1.8 at day 4 and 7, which were significantly lower than 20.0 ± 2.7 and 13.3 ± 2.4 in the CN group, respectively (t = 3.3, 2. 8, P < 0.05). The APACHE Ⅱ scores of patients in the IRN group at day 10and 14 were also lower than those in the CN group, while there was no significant difference (t =0. 7, 0. 6, P>0.05). The incidences of pulmonary and abdominal infection and surgical intervention rate in the IRN group were 18% (7/40), 13% (5/40) and 5% (2/40), which were significantly lower than 38% (15/40), 33% (13/40)and 20% (8/40) in the CN group, respectively (χ2 =4.0, 4.6, 4.1, P<0.05). The incidence of sepsis in the IRN group was 5% (2/40), which was lower than 8% (3/40) of the CN group, while there was no significant difference between the two groups ( χ2 =0.0, P >0.05 ). The average lengths of ICU and hospital stay in the IRN group were (5.4 ± 1.6 ) days and ( 38.6 ± 9.3 ) days, which were significantly lower than ( 7.8 ± 2.8 ) days and (43.1 ± 1 1.6) days in the CN group, respectively ( t = 2. 7, 3. 7, P < 0.05 ). The morality was 5% (2/40) in the IRN group and 8% (3/40) in the CN group, with no significant difference between the two groups (χ2 =0.0,P >0.05). Conclusion CN support supplemented with ω-3 PUFA and glutamine can adjust the inflammation reaction of SAP and sustain the normal immune function, which is helpful in decreasing the incidence of severe infection.

The current study was designed to determine the safety, tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone [rhPTH (1-84)] used for the treatment of osteoporosis. In the single-dose format pharmacokinetic study, thirty-six healthy male volunteers received three dose levels of rhPTH (1-84) subcutaneously: 1, 2, and 4 mug/kg. The blood was timing drawn and the serum concentration of rhPTH (1-84) was determined by enzyme linked immunosorbent assay (ELISA). Serum concentration-time curves of PTH (1-84) exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration. Serum terminal half-time of PTH (1-84) was approximately 2 h. The parameters indicated the serum levels were directly proportional to the administered dose, with the mean C(max) and AUC(0-24) ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg.h.mL(-1) over the dose range. The drug was well tolerated, the clinical symptoms were generally mild and of short duration.

Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.kg, and 220 microg/kg plus 2.5 microg/min.kg) in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPIIb/IIIa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
Injections, Intravenous ; Peptides, Cyclic/*pharmacokinetics ; Peptides, Cyclic/*pharmacology ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/*pharmacokinetics ; Platelet Aggregation Inhibitors/*pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors ; Young Adult

Batifiban,a synthetic cyclic peptide,is a potent platelet glycoprotein GPⅡb/Ⅲa an-tagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects,and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55,110,or 220 μg/kg,or multiple doses of an bolus followed intravenous infusion for 24 h (180 μg/kg of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma lev-els of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner,consistent with its mechanism as a GP Ⅱb/Ⅲa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.

h. The parameters indicated the serum levels were directly proportional to the administered dose, with the mean Cmax and AUC0-24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 mild and of short duration.

OBJECTIVE: To establish RP-HPLC method for the content determination of chlorogenic acid in 3 kinds of dosage forms of Qingkailing preparation. METHODS: SinoChrom ODS-AP C18(250 mm?4.6 mm, 5 ?m) column was adopted and the mobile phase consisted of methnol-water-acetic acid (25 ∶ 75 ∶ 0.5) at the flow rate of 1.0 mL?min-1. Column temperature was set at 30 ℃ and the detection wavelength was set at 327 nm. RESULTS: The linear range of chlorogenic acid was 3.81～152.50 ?g?mL-1(r=0.999 8), and the average recoveries of the capsules, granules and dripping pills were 99.03%(RSD=2.02%), 99.35%(RSD=1.16%),98.11%(RSD=1.51%). CONCLUSION: The method is sensitive, simple and accurate for the quality control and content determination of 3 kinds of Qingkailing preparations.