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* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

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.

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.

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.

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 .

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.

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.

Objective To explore the influence of agricultural mechanization progress on epidemic intensity of hemorrhagic fever with renal syndrome (HFRS) so as to provide reference for prevention and control of HFRS in rural areas.Methods Data of HFRS epidemics and agricultural mechanization progress of Qingdao City and five main epidemic areas of HFRS were collected by retrospective analysis methods.Agricultural mechanization progress,time distribution,incidence rate of HFRS and capture rate of rats were compared,respectively.Risk factors were analyzed by case-control study using simple random sampling method.Cases of case group were selected from HFRS cases of Jiaonan County recovered between 2012 and 2013.The control group was healthy residents with a equal number of the case group.Residential locations,work ways,rodent infestation at work locations and in residential areas and skin injury conditions were surveyed by a household questionnaire survey.Results Agricultural machinery gross power of Qingdao City was developed from 174.76 megawatts of electricity (mwe) in 1985 to 854.00 mwe in 2015.The comprehensive mechanization degree marched from 60.0％ in 1994 to 90.2％ in 2015.HFRS incidence in Qingdao City declined from the first epidemic peak (1986) of 32.97/100 000 to the third peak (2012) of 3.54/100 000.HFRS incidence in Jiaonan,Jiaozhou,Pingdu,Laixi,Jimo cities reduced from the first epidemic peak (1985 or 1986) of 101.25/100 000,86.37/100 000,35.80/100 000,11.55/100 000,8.13/100 000 to the third peak(2012) of 14.68/100 000,4.43/100 000,2.33/100 000,6.02/100 000,3.26/100 000.The platform stage of epidemic peak in autumn and winter shortened from 4 or 5 months to 2 months.The capture rate of rats fluctuated around 2％.The infection risk of small farm implements or handwork was greater than huge mechanization (OR =0.01,P ＜ 0.01).Conclusions Agricultural mechanization changes the agricultural activity patterns to a large extent and lowers the HFRS epidemic by minimizing the risk of infection and shortening the platform stage of epidemic peak.The higher the degree of mechanization,the lower the epidemic intensity.

Objective To evaluate the relationship between anterior chamber angle and intraocular pressure (IOP) after laser peripheral iridotomy (LPI) treatment.Methods A retrospective cases control study was adopted.Fifty-eight patients (58 eyes) who were diagnosed as primary angle closure (PAC) were included in this study.Ultrasound biomicroscopy (UBM) parameters in angle opening distance (AOD),trabecular iris area (TISA) and angle recess area (ARA) examination were performed before LPI.The changes of intraocular pressure (IOP) were compared between different time-points (before and 1 hour,2 hours,8 hours,24 hours,2 weeks,6 months and 12 months after LPI).The patients were divided into IOP≤21 mmHg group (41 eyes) and IOP＞21 mmHg group (17 eyes) after LPI.Relationship between anterior chamber angle and IOP after LPI treatment was explored.This study was approved by Ethic Committee of the Henan Eye Institute and informed consent was obtained from each patient.Results The IOPs were increased in 1 hour,2 hours after LPI and lowered in 2 weeks,6 months,12 months after LPI compared with IOP before LPI,with significant differences between them (all at P＜0.01).Twelve patients suffered transient elevated IOP and recovered by self-healing or treatment.IOP of 4 patients were elevated after 6 months to 1 year follow-up.The IOPs in 2 weeks,6 months and 12 months after LPI were lowered compared with IOP before LPI,with significant differences between them (all at P＜0.01).The UBM parameters were significantly increased in 2 weeks,6 months,12 months after LPI in comparison with IOP before IPL (all at P＜0.01).IOP and UBM parameters values were significantly different between IOP＞21 mmHg group and ≤21 mmHg group after LPI.Regression analysis indicated that ARA750 (OR =0.75,P＜0.05) was correlated to the IOP after LPI rather than IOP before operation,AOD and TISA (P＞0.05).Conclusions ARA750 value is correlated with the IOP variations after LPI.UBM structured observation can improve the surgical successful rates and safty and prevent complications.

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.