1.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug-drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage*
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Drug Monitoring/methods*
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Humans
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Organ Transplantation
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Immunosuppressive Agents/administration & dosage*
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Delphi Technique
2.Formulation and Explanation of the Standards for Hospital Pharmacy Research
Yan LI ; Shiting LIU ; Yilei LI ; Wei ZHANG ; Weiyi FENG ; Yalin DONG ; Rongsheng ZHAO ; Wan-sheng CHEN ; Houwen LIN ; Jin LU ; Boxin ZHAO ; Xin HUANG ; Jiancun ZHEN
Herald of Medicine 2025;44(5):716-719
Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.
3.Formulation and Explanation of the Standards for Hospital Pharmacy Research
Yan LI ; Shiting LIU ; Yilei LI ; Wei ZHANG ; Weiyi FENG ; Yalin DONG ; Rongsheng ZHAO ; Wan-sheng CHEN ; Houwen LIN ; Jin LU ; Boxin ZHAO ; Xin HUANG ; Jiancun ZHEN
Herald of Medicine 2025;44(5):716-719
Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.
4.Development of a prediction model to identify undiagnosed chronic obstructive pulmonary disease patients in primary care settings in China
Buyu ZHANG ; Dong SUN ; Hongtao NIU ; Fen DONG ; Jun LYU ; Yu GUO ; Huaidong DU ; Yalin CHEN ; Junshi CHEN ; Weihua CAO ; Ting YANG ; Canqing YU ; Zhengming CHEN ; Liming LI
Chinese Medical Journal 2023;136(6):676-682
Background::At present, a large number of chronic obstructive pulmonary disease (COPD) patients are undiagnosed in China. Thus, this study aimed to develop a simple prediction model as a screening tool to identify patients at risk for COPD.Methods::The study was based on the data of 22,943 subjects aged 30 to 79 years and enrolled in the second resurvey of China Kadoorie Biobank during 2012 and 2013 in China. We stepwisely selected the predictors using logistic regression model. Then we tested the model validity through P-P graph, area under the receiver operating characteristic curve (AUROC), ten-fold cross validation and an external validation in a sample of 3492 individuals from the Enjoying Breathing Program in China.Results::The final prediction model involved 14 independent variables, including age, sex, location (urban/rural), region, educational background, smoking status, smoking amount (pack-years), years of exposure to air pollution by cooking fuel, family history of COPD, history of tuberculosis, body mass index, shortness of breath, sputum and wheeze. The model showed an area under curve (AUC) of 0.72 (95% confidence interval [CI]: 0.72-0.73) for detecting undiagnosed COPD patients, with the cutoff of predicted probability of COPD=0.22, presenting a sensitivity of 70.13% and a specificity of 62.25%. The AUROC value for screening undiagnosed patients with clinically significant COPD was 0.68 (95% CI: 0.66-0.69). Moreover, the ten-fold cross validation reported an AUC of 0.72 (95% CI: 0.71-0.73), and the external validation presented an AUC of 0.69 (95% CI: 0.68-0.71).Conclusion::This prediction model can serve as a first-stage screening tool for undiagnosed COPD patients in primary care settings.
5.Study on the Synthesis of Shikimic Acid Derivatives and Their Reversal Effects on Paclitaxel-resistant Human Breast Cancer Cells
Lu ZHANG ; Siying CHEN ; Qian WANG ; Jin ZHANG ; Liying HUANG ; Le REN ; Huiping TIAN ; Nan WANG ; Yalin DONG
China Pharmacy 2020;31(8):945-952
OBJECTIVE:To struc turally modify shikimic acid ,and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS :Using shikimic acid as the lead structure ,1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ,amidation, hydrogenation and reduction ,etc. Using non-drug resistant cells MCF- 7 as reference ,MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration (IC50)and reversal index (RI)of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ,the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS :Totally 15 derivatives were obtained (T1-T15), of which T 4-T15 were obtained for the first time. MTT assay showed that (3R, 4S, 5R) -N-benzyl-3, 4, 5-trihydroxy-1-cyclohexene-1-formamide(T7),(3R,4S,5R)-N-(3,4,5-trihydroxy-1-cyclohexenylmethyl)-benzylamine(T14), (3R,4S,5R)-3,4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate (T15)inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ;IC50 values of T 7,T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control (Paclitaxel alone )group(P<0.05). RIs of T 14 and T 15 were higher ,and RIs of the highest dose were 8.8 and 9.3, which were equivalent to positive control verapamil (10.8). Th e results of molecular docking showed that the hydroxyl groups at positions 3,4 of T 7 could form multiple hydrogen bonds with ; Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7,the mail:batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ,the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS : The derivatives T 7,T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .
6.Analysis on rationality of antihyperuricemic drugs application and detection of HLA-B*5801 alleles in patients with chronic kidney diseases complicated by hyperuricemia
Di ZHANG ; Siying CHEN ; Zhihua YANG ; Wanhong LU ; Yalin DONG
Adverse Drug Reactions Journal 2019;21(1):15-19
Objective To analyze the rationality of antihyperuricemic drugs application and HLA-B*5801 alleles detection in patients with chronic kidney diseases complicated by hyperuricemia. Methods The medical records of patients with chronic kidney diseases complicated by hyperuricemia in the First Affiliated Hospital of Xi′an Jiaotong University from July 2015 to June 2017,whose HLA-B*5801 alleles were detected and who were treated with benzbromarone,allopurinol,or febuxostat,were collected and analyzed retrospectively. The evaluation criteria of rationality of 3 antihyperuricemic drugs application and gene detection were constituted according to the related guidelines,expert consensuses,and drug labels. It was judged as irrational use of benzbromarone in patients with estimating glomerular filtration rate (eGFR)< 30 ml/(min · 1. 73 m2 ),excessive uric acid production,acute gout attack,urinary calculi,or undetermined uric acid excretion type. It was judged as irrational use of allopurinol in patients whose eGFR were < 15 ml/(min·1. 73 m2 )but without dialysis or in patients with positive HLA-B*5801 alleles. It was judged as irrational use of gene detection in patients who had underwent gene detection but were not suitable for allopurinol treatment after initial assessment,and in patients who finally were not given allopurinol though they were suitable for allopurinol treatment after initial assessment and with negative HLA-B*5801 alleles. Results A total of 201 patients enrolled in the study. There were 57,103,and 41 patients receiving benzbromarone,allopurinol,and febuxostat,respectively. There were 24 (11. 9%)patients with positive HLA-B*5801 alleles and 177 (88. 1%)with negative one. The percentages of patients with rational use of benzbromarone,allopurinol,and febuxostat were 40. 4% (23/ 57),76. 7% (79/ 103)and 100% (41/ 41), respectively. The percentage of patients with rational use of HLA-B*5801 alleles detection was 50. 2%(101 / 201). There were 100 patients with irrational use of HLA-B*5801 alleles detection,including 34 patients who underwent gene detection but were not suitable for allopurinol treatment [their eGFRs were <15 ml/(min·1. 73 m2 )but they did not conduct dialysis],and 66 patients who were not given allopurinol despite that they were suitable for allopurinol treatment with negative HLA-B*5801 alleles. Conclusions There are irrational use of both antihyperuricemic drugs and HLA-B*5801 alleles detection in patients with chronic kidney diseases complicated by hyperuricemia in our hospital. Irrational use of benzbromarone is more serious in antihyperuricemic drugs. Clinicians should pay attention to the irrational use of antihyperuricemic drugs.
7.Analysis on rationality of antihyperuricemic drugs application and detection of HLA-B*5801 alleles in patients with chronic kidney diseases complicated by hyperuricemia
Di ZHANG ; Siying CHEN ; Zhihua YANG ; Wanhong LU ; Yalin DONG
Adverse Drug Reactions Journal 2019;21(1):15-19
Objective To analyze the rationality of antihyperuricemic drugs application and HLA-B*5801 alleles detection in patients with chronic kidney diseases complicated by hyperuricemia. Methods The medical records of patients with chronic kidney diseases complicated by hyperuricemia in the First Affiliated Hospital of Xi′an Jiaotong University from July 2015 to June 2017,whose HLA-B*5801 alleles were detected and who were treated with benzbromarone,allopurinol,or febuxostat,were collected and analyzed retrospectively. The evaluation criteria of rationality of 3 antihyperuricemic drugs application and gene detection were constituted according to the related guidelines,expert consensuses,and drug labels. It was judged as irrational use of benzbromarone in patients with estimating glomerular filtration rate (eGFR)< 30 ml/(min · 1. 73 m2 ),excessive uric acid production,acute gout attack,urinary calculi,or undetermined uric acid excretion type. It was judged as irrational use of allopurinol in patients whose eGFR were < 15 ml/(min·1. 73 m2 )but without dialysis or in patients with positive HLA-B*5801 alleles. It was judged as irrational use of gene detection in patients who had underwent gene detection but were not suitable for allopurinol treatment after initial assessment,and in patients who finally were not given allopurinol though they were suitable for allopurinol treatment after initial assessment and with negative HLA-B*5801 alleles. Results A total of 201 patients enrolled in the study. There were 57,103,and 41 patients receiving benzbromarone,allopurinol,and febuxostat,respectively. There were 24 (11. 9%)patients with positive HLA-B*5801 alleles and 177 (88. 1%)with negative one. The percentages of patients with rational use of benzbromarone,allopurinol,and febuxostat were 40. 4% (23/ 57),76. 7% (79/ 103)and 100% (41/ 41), respectively. The percentage of patients with rational use of HLA-B*5801 alleles detection was 50. 2%(101 / 201). There were 100 patients with irrational use of HLA-B*5801 alleles detection,including 34 patients who underwent gene detection but were not suitable for allopurinol treatment [their eGFRs were <15 ml/(min·1. 73 m2 )but they did not conduct dialysis],and 66 patients who were not given allopurinol despite that they were suitable for allopurinol treatment with negative HLA-B*5801 alleles. Conclusions There are irrational use of both antihyperuricemic drugs and HLA-B*5801 alleles detection in patients with chronic kidney diseases complicated by hyperuricemia in our hospital. Irrational use of benzbromarone is more serious in antihyperuricemic drugs. Clinicians should pay attention to the irrational use of antihyperuricemic drugs.
8.Analysis of Risk Factors and Clinical Outcome for Carbapenems-resistant Pseudomonas aeruginosa Infection in Our Hospital from 2013 to 2016
Saisai LUO ; Qiaowei ZHENG ; Yalin DONG ; Youxia WEI
China Pharmacy 2018;29(5):667-670
OBJECTIVE: To investigate the risk factors and clinical outcome for carbapenems-resistant Pseudomonas aeruginosa (CRPA) infection, and to provide reference for the prevention and treatment of CRPA infection.METHODS: In retrospective investigation, medical records of CRPA and carbapenems-sensitive Pseudomonas aeruginosa (CSPA) infection were collected from our hospital during 2013-2016. CRPA infection risk factors were judged by single factor analysis. The relationship of CRPA risk factors and death was judged by multivariate Logistic regression analysis. RESULTS: A total of 556 cases of P. aeruginosa infection were collected, including 96 cases of CRPA injection, accounting for 17. 3%. Multivariate Logistic regression analysis of related factors of CRPA infection showed that independent risk factors of CRPA infection included admission to ICU for more than 3 days before the isolation of P. aeruginosa [OR= 2. 691, 95% CI (1. 348, 5. 373), P=0. 005], the use of third-generation or fourth-generation cephalosporin [OR= 0. 386, 95% CI (0. 200, 0. 742), P=0. 004], complicated with other pathogenic bacteria infection [OR= 1. 892, 95% CI (1. 132, 3. 164), P=0. 015], combined with 2 kinds of antibiotics or above [OR=5. 631, 95% CI (2. 556, 12. 407), P=0. 000]. Clinical outcome analysis, mortality rate of CRPA infection were 12. 5%, significantly higher than CSPA infection (2. 8%), Logistic regression analysis, there is a correlation between death rate [OR=5. 003, 95%CI (1. 975, 12. 675), P=0. 001] and CRPA infection. CONCLUSIONS: For the prevention of CRPA nosocomial infection, it is necessary to reduce the time of ICU stay and rationally select antibiotics according to pathogenic bacteria so as to reduce the occurrence of CRPA infection.
9.Analysis of Risk Factors for Carbapenem-resistant Acinetobacter baumannii Infection in a Third Grade Class A Teaching Hospital
Yuchen LI ; Ying LI ; Jiao XIE ; Yalin DONG
China Pharmacy 2018;29(7):984-986
OBJECTIVE:To study risk factors for carbapenem-resistant Acinetobacter baumannii(CRAB)infection,and to provide reference for its clinical prevention. METHODS:In retrospective study,302 A. baumannii(AB)infection patients were collected from our hospital during Dec. 2012 to Jun. 2017. According to the results of drug sensitivity test,those patients were divided into CRAB group(116 cases)and non-CRAB group(186 cases). Risk factors for CRAB infection were analyzed by using univariate analysis. Multivariate Logistic regression analysis was performed for variables with significant difference between 2 groups. RESULTS:Univariate analysis showed that the factors of significant difference in 2 groups including patients suffering from septic shock(P=0.003),sepsis(P=0.000),combined with other infection(P=0.006),diabetes(P=0.029),malignant tumors(P=0.036),patients suffering from infection of other site except for pulmonary infection,intraabdominal infection and skin infection(P=0.009)before AB isolation,patients given carbapenems(P=0.002)and antifungal drugs 28 d before AB isolation(P=0.002). Multivariate Logistic regression analysis showed that the factors of significant difference in 2 groups including patients suffering from sepsis(P=0.033)or diabetes(P=0.011)before AB isolation. CONCLUSIONS:Independent risk factors for CRAB infection include patients suffer from sepsis or diabetes before AB isolation.
10.Effect of parecoxib sodium on serum surfactant protein A and inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy
Shuaiguo LYU ; Xihua LU ; Tieli DONG ; Tingkun LI ; Lei WANG ; Yalin SUN ; Dandan WANG
The Journal of Clinical Anesthesiology 2018;34(1):50-53
Objective To investigate the effects of perioperative parecoxib sodium on serum surfactant protein A and inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy,Methods Sixty-two ASA Ⅰ or Ⅱ elderly patients,aged 65-78 years,weighing 51-79 kg,scheduled for elective video-assisted thoracoscopic pneumonectomy under general anesthesia,were randomly divided into 3 groups:0.3 mg/kg parecoxib sodium group (group P1,n=21),0.6 mg/kg parecoxib sodium group (group P2,n =21) and control group (group C,n =20).The patients were given intravenous parecoxib sodium of 0.3 mg/kg immediately before induction of anesthesia and at 12 h after operation in group P1,and also parecoxib sodium of 0.6mg/kg immediately before induction of anesthesia and at 12 h after operation in group P2,while the equal volume of normal saline was given in group C.Blood samples were taken from the central vein before the induction of anesthesia(T0),after operation(T1),12 h after operation(T2) and 24 h after operation(T3).The concentration of serum surfactant protein A (SP-A),TNF-α,IL-6 and IL-8 were determined by ELASA.The incidence of pulmonary complications at 72 h after operation were also recorded.Results Compared with T0,the concentration of serum SP-A,TNF-α,IL-6 and IL-8 increased significantly in all groups at T1-T3 (P<0.05).Compared with C group,the concentration of serum SP-A,TNF-α,IL-6 and IL-8 in groups P1 and P2 decreased significantly at T1-T3 (P<0.05),there were no significant differences between groups P1 and P2.The incidence of postoperative pulmonary complications had no statistically significant differences between the three groups.Conclusion Parecoxib sodium can significantly reduce the concentration of serum SP-A and alleviate the inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy.

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