Genome-wide analysis of long non-coding RNAs involved in the fruit development process of Cucumis melo Baogua.

Melon (Cucumis melo L.) is a horticultural crop that is planted globally. Cucumis melo L. cv. Baogua is a typical melon that is suitable for studying fruit development because of its ability to adapt to different climatic conditions. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs longer than 200 nucleotides, which play important roles in a wide range of biological processes by regulating gene expression. In this study, the transcriptome of the Baogua melon was sequenced at three stages of the process of fruit development (14 days, 21 days, and 28 days) to study the role of lncRNAs in fruit development. The cis and trans lncRNAs were subsequently predicted and identified to determine their target genes. Notably, 1716 high-confidence lncRNAs were obtained in the three groups. A subsequent differential expression analysis of the lncRNAs between the three groups revealed 388 differentially expressed lncRNAs. A total of 11 genes were analyzed further to validate the transcriptome sequencing results. Interestingly, the MELO3C001376.2 and MSTRG.571.2 genes were found to be significantly (P < 0.05) downregulated in the fruits. This study provides a basis to better understand the functions and regulatory mechanisms of lncRNAs during the development of melon fruit.

Therapeutic drug monitoring of vancomycin: a guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Guideline development should be based on the quality of evidence, balance of benefits and harms, economic evaluation and patients' views and preferences. Therefore, these factors were considered in the development of a new guideline for therapeutic drug monitoring (TDM) of vancomycin. OBJECTIVES: To develop an evidence-based guideline for vancomycin TDM and to promote standardized vancomycin TDM in clinical practice in China. METHODS: We referred to the WHO Handbook for Guideline Development and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and grade the strength of recommendations, according to economic evaluation and patients' views and preferences. We used the GRADE Grid method to formulate the recommendations. RESULTS: The guideline presents recommendations about who should receive vancomycin TDM, how to monitor vancomycin efficacy and renal safety, therapeutic trough concentrations, time to start initial vancomycin TDM, loading dose and how to administer and adjust the vancomycin dose. CONCLUSIONS: We developed an evidence-based guideline for vancomycin TDM, which provides recommendations for clinicians and pharmacists to conduct vancomycin TDM in China.

Correlation of thiopurine methyltransferase activity and 6-thioguanine nucleotide concentration in Han Chinese patients treated with azathioprine 25 to 100 mg: A 1-year, single-center, prospective study.

BACKGROUND: Of the enzymes involved in the metabolism of azathioprine, thiopurine methyltransferase (TPMT) is the one characterized by genetic polymorphisms and ethnic variations. There have been several studies of the ethnic variations in phenotype and genotype of TPMT, although few have assessed the possible correlation between TPMT activity and 6-thioguanine nucleotide (6-TGN) concentrations. OBJECTIVE: The aim of this study was to examine the relationship between TPMT activity and the steady-state concentration (Css) of 6-TGN, the primary active metabolite of azathioprine, in red blood cells (RBCs) in Han Chinese patients treated with azathioprine. METHODS: Han Chinese patients aged 18 to 60 years with immunosuppression and normal hepatic and renal function who had been receiving a stable dose (25-100 mg/d) of oral azathioprine as a part of their regular anti-immunosuppression regimen for at least 10 days were recruited for this 1-year, single-center, prospective study. Azathioprine was administered PO QD in the morning, in combination with a stable regimen of other immunosuppressive drugs, for 1 year. At 1 year, blood samples were drawn just before the ingestion of azathioprine. TPMT activity and 6-TGN Css in RBCs were determined in our laboratory using high-performance liquid chromatography. Adverse drug events were monitored by a patient questionnaire and laboratory testing. Out of the initial cohort, several patients were concurrently enrolled in a subanalysis in which the effect of TPMT polymorphism on the pharmacokinetic properties of 6-mercaptopurine, the intermediate metabolite of azathioprine, was examined. RESULTS: Nineteen patients (14 women, 5 men; mean [SD] age, 41 [9.6] years [range, 22-59 years]; mean [SD] weight, 62 [12] kg) were included in the study; 7 were included in the subanalysis. A significant negative correlation was found between TPMT activity and 6-TGN Css in RBCs (r = -0.712; P = 0.001); when the outlier data were removed, no significant correlation was found. Mean (SD) TPMT activity was 12.95 (3.07) nmol/h · mL(-1) RBCs and the interindividual CV was 23.68%. Mean (SD) 6-TGN CSS was 42.95 (41.98) ng/8 × 108 RBCs and the interindividual CV was 97.74% (N = 19), while the intraindividual CV of 6-TGNs within 8 hours after azathioprine ingestion was between 4.23% and 7.37% (n = 7). No significant correlation was found between 6-TGN Css in RBCs and the dose of azathioprine used. One patient's treatment was discontinued because her white blood cell count decreased to < 4 × 109 cells/L, indicating myelotoxicity; the t/12 of 6-TGNs in this patient was 5.85 days. Treatment was well tolerated by all other patients. CONCLUSION: In this small study, a significant negative correlation was found between TPMT activity and 6-TGN concentration in the RBCs of these Han Chinese patients. However, the correlation was not significant when data from 1 patient with low TPMT activity were excluded.

Pharmacokinetics and relative bioavailability of salbutamol metered-dose inhaler in healthy volunteers.

AIM: To study the pharmacokinetics and relative bioavailability of salbutamol metered-dose inhaler (MDI) in healthy volunteers. METHODS: An HPLC method for the determination of salbutamol in human plasma was improved. Ten healthy male Chinese volunteers were enrolled in a randomized crossover study. After the subjects inhaled or orally administered 1.2 mg salbutamol, fourteen blood samples were collected at predetermined time points. The concentrations of salbutamol in plasma were assessed with non-compartment model to obtain the pharmacokinetic parameters. The relative bioavailability of MDI versus water solution was calculated. RESULTS: The HPLC assay was sensitive, specific, accurate, and precise. The pharmacokinetics of salbutamol MDI was described well with two-compartment model. The parameters for salbutamol inhaled and orally administered were as following: T(max) (0.22+/-0.07) and (1.8+/-0.6) h, C(max) (3.4+/-1.1) and (3.9+/-1.4) microg/L, T(1/2) (4.5+/-1.5) and (4.6+/-1.1) h, AUC0-20 min (0.9+/-0.3) and (0.16+/-0.10) microg x h x L(-1), respectively. There were significant differences in T(max) and AUC0-20 min between the two dosage forms. The AUC0-20 min (inhal) was 8 times as high as the AUC0-20 min (po). The relative bioavailability of salbutamol MDI was 57 %+/-24 % compared with oral solution. CONCLUSION: The absorption process of salbutamol MDI in human was significantly different from that of oral solution.