Trypanosoma is a human parasite severely affecting poor tropical areas.However,current frontline drugs for Trypanosoma treatment have severe side-effects with decreased effectiveness.Based on the fact that aminoacyl-tRNA synthetase is a bonafide drug target for several microorganisms,including bacteria and fungi,it is plausible that it may also be effective target of Trypanosoma.The Trypanosoma brucei leucyl-tRNA synthetase(tbLeuRS)was cloned,expressed and purified to develop an in vitro enzymatic assay system.The assay conditions were further optimized for the effective screening of tbLeuRS inhibitors thus establishing an anti-Trypanosoma drug screening system targeting tbLeuRS.The results indicated that this system can be employed for the effective screening of anti-Trypanosoma drugs with satisfactory specificity.In addition,this system can also be used for compound optimization,as well as IC50 testing.Using this system a series of compounds are identified that are effective Trypanosoma inhibitors without toxicity to human cells.Therefore,targeting tbLeuRS may represent a new venue for the development of anti-Trypanosoma drugs.

Objective To decrease the incidence of acute rejection in renal allograft recipients by monitoring of cyclosporine A (CsA) concentration at 2-hour after dosing(C2). Methods The CsA C2 and CsA trough concentration(C0) were assayed in renal allograft recipients.All patients were followed up for at least 1 year.The correlation of C0 and C2 monitoring with clinical outcomes was analyzed. Results At 1 week and 1 month post-transplantation,the incidence of acute rejection in patients with C2 in target level was 4.41% and 10.29%, respectively,but the incidence of acute rejection in patients with C2 in lower level was 42.37% and 36.20%,respectively. ConclusionBy reflecting the drug exposure of CsA more accurately,C2 monitoring is beneficial for decreasing the incidence of acute rejection after renal allograft transplantation.

Objective To investigate the characteristic and clinical significance of airway inflammation in children with acute asth-ma. Methods Underwent sputum induction and sputum induction in children (n=34) with acute asthma was repented in recovered children ( n = 24).Induced sputum were also taken from 15 healthy children as controls.Total and differential cell counts were per-formed. Interleukin(IL)-8、IL-6 were measured,The relationship between inflammatory cells and IL-8、 IL-6、peak expiratory (PEF) were analyzed.Results The inflammatory cell infiltrate was mixed including eosmophilic granulocytes, neutrophils, and macrophages. They decreased significantly, but eosinophilic granulocyte remained a higher percentage compared with healthy subjects. There was low-er percentage of lymphocytes at acute exacerhation.Eosinophilic granulocytes were correlated with the degree of airflow obstruction. Levels of IL-8、IL-6 were elevated during the acute exacerbation and decreased at resolution.IL-8 was correlated significantly with neutrophils at acute exacerhation and resolution.IL-6 was correlated signifficantly with eosinophilic granulocytes at acute exacerbation. Conclusions Airway inflammation is chataeterized by infiltration of eosinophils, neutrophils and macrophages.IL-8、IL-6 possibly is the important cytokines of airway inflammation in children with acute asthma. Increased eosinophils in induced sputum correlates with asthma severity. Therapy to the cytokines may have potential values.J Appl Clin pediatr,2004,19(12): 1023-1025

To explore the effect of different processing methods and conditions of coumarin and volatile compounds in Angelica Dahuricae Radix and their change regularity, in order to optimize and establish appropriate drying methods and conditions. After being cleaned, fresh Angelica Dahuricae Radix herbs were baked, sun-dried, shade-dried, sun-dried after sulfur-fumigation, dried by quick-lime embedding, freeze-dried, microwave-dried. Finally, 24 groups of samples were obtained after being mashed and passing through the 60-mesh screen. The HPLC-PDA method was adopted to simultaneously determine the content of coumarin compounds. The GC-MS method was used to determine the content of volatile compounds. The principal component analysis (PCA) was made on the standardized analysis results for the 24 groups of samples processed with different drying methods. According to the PCA results, the comprehensive scores of coumarin and volatile compounds in Angelica Dahuricae Radix herbs processed with different methods in the order from high to low were that unpeeled and dried by quicklime embedding > unpeeled and dried with hot-air at 100 degrees C > unpeeled and dried with hot-air at 40 degrees C > peeled and infrared-dried > peeled and dried with hot-air at 60 degrees C > peeled and dried with hot-air at 40 degrees C > peeled and sun-dried > peeled and dried with hot-air at 60 degrees C > peeled and dried with hot-air at 100 degrees C > peeled and microwave-dried > peeled and dried with hot-air at 80 degrees C > unpeeled and sun-dried > unpeeled and dried with sulfur-fumigation > peeled and dried with sulfur-fumigation > unpeeled and dried with hot-air at 120 degrees C > unpeeled and freeze-dried > unpeeled and infrared-dried > peeled and dried with hot-air at 120 degrees C > peeled and freeze-dried > peeled and dried by quicklime embedding > unpeeled and dried with hot-air at 80 degrees C > peeled and shade-dried > unpeeled and shade-dried > unpeeled and microwave-dried. According to the findings, different drying processing methods have certain impacts on the content coumarin and volatile compounds in Angelica Dahuricae Radix herbs. The traditional method of drying by quicklime embedding is recommended as the optimum origin processing method of Angelica Dahuricae Radix, which is followed by the method for being peeled and dried with hot-air at 100 degrees C.
Angelica ; chemistry ; Coumarins ; analysis ; Desiccation ; methods ; Gas Chromatography-Mass Spectrometry ; Hot Temperature ; Principal Component Analysis ; Volatile Organic Compounds ; analysis

Objective To explore the matrix effect on cyclosporine A (CsA) test by fluorescence polarization immunoassay (FPIA) and enzyme-multiplied immunoassay technique (EMIT), explain the discrepancy of external quality control results between these two methods and find the corrective action.Methods One hundred whole blood samples with various concentrations were adopted and CsA levels were detected by FPIA and EMIT.The results were compared with each other.Moreover, the influence of residual metal ions upon immunoreactions was assessed by adding Cu2+ and Zn2+.The effect of non-whole blood matrix on extraction efficiency for quality control materials and CsA calibrator was evaluated by adding identical volume of Hb-rich reagents followed with re-extraction.Results There is good correlation between results measured with FPIA(X) and EMIT(Y) methods ( Y=0.926 8X -8.115,R2 =0.996 9).Neither FPIA nor EMIT was affected by residual metal ions ( P ＞ 0.05 ). Non-whole blood matrix decreased the extraction efficiency of two methods, but it could be corrected by supplementation of the Hb-rich reagents (≥30 g/L).Conclusions Non-whole blood matrix may be the main reason for the inconsistent results measured by FPIA and EMIT methods.It could be corrected by using Hb-rich reagents.In addition,we should consider the influence of low lib on CsA test,espocially for organ transplant patients with lower Hb ( ＜30 g/L).

OBJECTIVE To investigate the effective treatment for secretory otitis media. METHODS 63 patients (78 ears)with secretory otitis media were randomly devided into two groups: The experimental group :Thirty-one patients (38 ears) were treated by eustachian tube insertion under nasal endoscope. Drugs were injected repeatedly through the pipe. The control group: 32 patients (40 ears) were treated by traditional method: the tympanic cavity pressure equalization tube. All patients were followed up for 6-9 months, the effectiveness was compared.RESULTS The experimental group: 16 ears (42.1 %) were cured, 18 ears (47.4 %) were straightened up, The total efficiency rate was 89.5 %. The control group: 8 ears (20.0 %) were cured, 21 ears (52.5 %) were straightened up, The total efficiency rate was 72.5 %. There were significant difference between the two groups after treatment (P

Objective To assess the indication and safety of surgical resection of the pregnancy by hysterotomy (SRPH) and hysterectomy for cesarean scar pregnancy (CSP). Methods A retrospective study of women with CSP was conducted at the Women′s Hospital, School of Medicine, Zhejiang University, from Jan. 2003 to Mar. 2016. The women underwent SRPH (SRPH group, n=35) and hysterectomy (Hysterectomy group, n=14) were included. The gestational age (GA), size of gestational mass(GM), level of serum β-hCG, previous treatments and clinical outcomes were analyzed. Results The median GA, the mean size of GM, median serum β-hCG level, median amount of blood loss, rate ot blood transfusion, rate of persistent CSP, and rate of motal status in SRPH group versus Hysterectomy group were 66 versus 84 days, (65 ± 22) versus (92±36) mm, 23755 versus 802 U/L, 400 versus 650 ml, 11%(4/35) versus 13/14, 49%(17/35) versus 12/14, 20% (7/35) versus 14/14, respectively (all P<0.05). In SRPH group, median amount of blood loss was 500 ml in patients with GA≥10 weeks versus 300 ml in patients with GA<10 weeks (P<0.05). Serious complication occurred in 7 patients: severe pelvic inflammation in 1 patient and hematomas in the uterine isthmus in 1 patient in SRPH group; severe pelvic inflammation in 2 patients and hemorrhagic shock and DIC in 3 patients in Hysterectomy group. No blaader damage occurred. Conclusions SRPH is effective and safe for patients with CSP with GA of 9-10 weeks, a diameter of 60-90 mm and stable hemodynamics. Hysterectomy is an alternative to SRPH for patiens in motal status with advanced GA more than 12 weeks.

Peptide drugs exhibit an irreplaceable role in clinics due to their high specificity, efficiency and low toxicity. At present, more than 80 peptide drugs have been approved for marketing with global sales exceeding $50 billion in 2019. However, with large molecular weights, high hydrophilicity and instability in digestive tract, oral peptide drugs encounter substantial physiological barriers leading to low oral bioavailability. Therefore, peptide drugs are mostly administered by parenteral routes. Although parenteral delivery of peptide drugs achieves high bioavailability, this is associated with inconvenience and discomfort, even causing severe side effects compared with the oral route possessing a high degree of patient compliance. Therefore, numerous studies concentrate on novel strategies to improve the oral bioavailability of peptide drugs. Some delivery technologies such as Eligen™ and Axcess™ have been successfully applied to the oral dosage form of therapeutic peptides and have accelerated relevant oral formulations for Food and Drug Administration (FDA) approval and clinical treatment. In this review, we focus on the oral peptide delivery, mainly summarizing the progress of recent strategies used to overcome oral barriers and the commercialization applications of related patents, which could facilitate the research and development (R&D) of clinical applications of oral delivery techniques for peptide drugs.

AIMTo investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam.

METHODSCYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately.

RESULTSAfter a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001).

CONCLUSIONCYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.

Adult ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C9 ; Genotype ; Glyburide ; pharmacokinetics ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Male ; Piroxicam ; analogs & derivatives ; pharmacokinetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length