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

Objective To analyze the expression,biological functions,and potential molecular regulatory mechanisms of synaptojanin-2 binding protein(SYNJ2BP)in epithelial ovarian cancer.Methods Clinical specimens from 73 patients treated at Rugao People's Hospital and Affiliated Hospital of Nantong University between September 2018 and September 2022 were collected,including 53 epithelial ovarian cancer tissues and 20 normal ovarian tissues.A retrospective analysis was performed to examine SYNJ2BP gene and protein ex-pression and its correlation with clinicopathological features.The effects of SYNJ2BP overexpression on pro-liferation,apoptosis,migration,and invasion abilities of epithelial ovarian cancer A2780 cells were assessed via CCK-8 assays,colony formation assays,cell cycle analysis,apoptosis assays,Transwell migration assays,and wound healing assays.Western blot was used to detect the impact of SYNJ2BP overexpression on ERK1/2 protein phosphorylation and c-Myc protein expression in A2780 cells.Results The expression of SYNJ2BP was significantly downregulated in epithelial ovarian cancer tissues,and its expression level was significantly correlated with FIGO stage,tumor grade,and histological type(P<0.05),but not with other clinicopatholog-ical features.CCK-8 and colony formation assays demonstrated that the proliferation level of A2780 cells in the pcDNA3.1-SYNJ2BP group was significantly lower than that in the pcDNA3.1-NC group(P<0.01).Flow cytometry with PI single staining revealed altered cell cycle distribution in A2780 cells of the pcDNA3.1-SYNJ2BP group,with cells arrested in the S phase and a significantly increased apoptosis ratio compared to the pcDNA3.1-NC group(P<0.05).Transwell assays showed that the number of A2780 cells invading through the artificial matrix membrane in the pcDNA3.1-SYNJ2BP group was approximately half that in the pcD-NA3.1-NC group(P<0.01).Western blot results indicated downregulated expression of ERK1/2 and c-Myc in A2780 cells of the pcDNA3.1-SYNJ2BP group compared to the pcDNA3.1-NC group.In nude mouse tumors of the pcDNA3.1-SYNJ2BP group,compared to the pcDNA3.1-NC group,SYNJ2BP expression was upregulated while ERK1/2 and c-Myc expression was downregulated,consistent with the cellular-level expres-sion results.Conclusion Low expression of SYNJ2BP is observed in epithelial ovarian cancer tissues,and overexpression of SYNJ2BP inhibits the proliferation and invasion abilities of epithelial ovarian cancer cells.This suggests that SYNJ2BP may serve as a potential tumor suppressor in epithelial ovarian cancer and could be considered as a prognostic typing marker or potential therapeutic target for ovarian cancer.

Objective:To develop the Clinical Nurse Extra Task Load Scale and test its reliability and validity.Methods:Based on the job demand-control model, a primary scale was formed through literature search and qualitative interviews, as well as Delphi consultation and pre-survey. In September 2023, 813 clinical nurses from First Affiliated Hospital of Xinxiang Medical University and Xinxiang Central Hospital were selected for reliability and validity testing. In October 2023, 1 050 clinical nurses from First Affiliated Hospital of Xinxiang Medical University and Xinxiang Central Hospital were selected for investigation, and the reliability and validity of the scale were tested.Results:The final Clinical Nurse Extra Task Load Scale included two dimensions and a total of 12 items. The item-level content validity index was 0.86 to 1.00, and the scale-level content validity index was 0.84. Exploratory factor analysis extracted two common factors, with a cumulative variance contribution rate of 74.55%. Confirmatory factor analysis showed that χ 2/ df was 1.613, GFI was 0.928, CFI was 0.971, NFI was 0.928, IFI was 0.971, and RMSEA was 0.024. Cronbach's α coefficient of the work environment demand dimension was 0.897, Cronbach's α coefficient of individual behavior restriction was 0.955, Cronbach's α coefficient of the total scale was 0.950, and the split-half reliability was 0.850. Conclusions:The Clinical Nurse Extra Task Load Scale developed has a good reliability and validity, and can be used to evaluate and quantify the extra task load for clinical nurses.

Objective To develop and validate a fatigue risk nomogram model in Chronic Obstructive Pulmonary Disease(COPD)patients.Methods A prospective study design was adopted,and 430 COPD patients recruited from a tertiary A hospital in Huzhou City from January to December 2022 were conveniently selected for model construction,and 129 patients were recruited from the same hospital from January to June 2023 for external validation of the model.The general information questionnaire,Pittsburgh Sleep Quality Index,2-item Generalized Anxiety Disorder Scale,2-item Patient Health Questionnaire,modified British Medical Research Council Dyspnea Index,International Physical Activity Questionnaire,and Fatigue Severity Scale were used for questionnaire survey.The risk prediction model and nomograms model were constructed using Logistic regression analysis and R 4.3.2 software,and the area under the receiver operating characteristic(ROC)curve was used to test the prediction effect of the model.Results Univariate and binary logistic regression analysis results showed that age(OR=1.095),gender(OR=2.077),dyspnea(OR=3.309),sleep quality(OR=1.979),anemia(OR=3.289),the number of acute exacerbation(OR=2.991)were independent influencing factors for fatigue in COPD patients.The internal evaluation and external validation results of the model showed that the areas under the curve are 0.912 and 0.844 respectively,and the Hosmer-Lemeshow goodness of fit test P values were 0.806 and 0.526 respectively.The average absolute errors were 0.013 and 0.019 respectively.Conclusion The COPD fatigue risk prediction model constructed in this study has good prediction effect.The visual nomogram is intuitive,convenient and easy to operate.It can provide a tool for early screening of fatigue in COPD patients.

Objective:To construct an estimating equation to accurately reflect the aging phenomenon of the glomerular filtration rate(GFR).Methods:Healthy subjects receiving physical examinations at the First Affiliated Hospital of Nanjing Medical University between January 2017 and April 2018 were included in the study, and the aging phenomenon of renal function indicators such as serum creatinine(Scr)was used as the reference standard to evaluate the accuracy of four Scr-based GFR equations during GFR aging, including the full age spectrum(FAS)equation, the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)equation, the Osaka equation and the Xiangya equation.Results:Of 37 636 individuals receiving physical examinations, 6 534 met the criteria specified in this study.Scr, serum urea nitrogen, serum uric acid, and serum albumin showed a significant aging phenomenon( H=191.640, 196.693, 83.271, 414.585, P<0.001 for all).The GFR estimated by the four equations all decreased with aging, but the starting point and rate of decline were significantly different.The GFR aging phenomenon estimated by the FAS equation was closer to the trend of renal function indicators. Conclusions:The FAS equation may be more applicable to healthy people to understand the aging phenomenon of GFR.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective:To evaluate the influence of sex on age-related changes in the glomerular filtration rate(GFR)in healthy individuals.Methods:A retrospective survey was performed.A total of 36 911 healthy subjects, of whom 43.61%(16 096 cases)were men, were enrolled and divided into six age groups: 18-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years old.The estimated glomerular filtration rate(eGFR)was evaluated by the full age spectrum(FAS)equation.General linear regression analysis was used to calculate the annual decline rate of eGFR, and differences between the sexes in the same age group were evaluated using analysis of covariance.The chi-square test was used to compare the proportions of subjects with different eGFR levels between the sexes.Results:Regardless of sex, body mass index(BMI), systolic blood pressure(SBP)and fasting blood glucose(FBG)all increased gradually with age, while diastolic blood pressure(DBP)increased initially and then turned downward.The means of above results in men were generally higher than those in women of the same age.Before the age of 40, the levels of eGFR in men and women were relatively stable, with the mean eGFR in women higher than that in men[(121.98±16.77)ml·min -1·1.73 m -2vs.(111.01±13.36)ml·min -1·1.73 m -2, t=-53.793, P=0.000]; After the age of 40, eGFR decreased with age in both sexes, and the decline rate of eGFR in women was faster than that in men before the age of 70.Men had generally higher mean serum creatinine(Scr), blood urea nitrogen(BUN)and serum uric acid(UA)than women.With the increase of age, BUN levels increased gradually in men and women, but Scr levels started to increase after the age of 40 only in women and did not show a clear increase in men. Conclusions:There are sex-related differences with aging, as measured with many parameters.Young and middle-aged women have significantly higher eGFR than men of the same age, but eGFR declines faster with aging in women.

Objective:To explore the effect of comorbidities on the risk of chronic kidney disease with aging.Methods:A total of 103 682 subjects were recruited at the health management center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020 for a retrospective cross-sectional study.Participants were divided into four groups according to age 18-44(55 055 case), 45-59(31 023 case), 60-74(12 793 case), ≥75(4 811 case)age group.We calculated and compared the prevalences of estimated glomerular filtration rate(eGFR)<60 ml/min/1.73m 2, which was used as a parameter for kidney dysfunction, indifferent age groups and participants with different comorbidities.The association between comorbidities and the prevalence of kidney dysfunction was analyzed by Logistic regression. Results:Levels of blood pressure, body mass index, serum creatinine, eGFR and blood lipids varied with aging, as did the prevalences of hypertension, diabetes, obesity and comorbidities.In all participants and groups based on the types of chronic diseases, the prevalence of kidney dysfunction increased with aging, substantially so in ≥75 age group.After adjustment for age and sex, there was a marked increase in the risk of kidney dysfunction in 45-59 age group adults with hypertension or diabetes( OR=9.163, 95% CI: 3.264-25.727; OR=4.640, 95% CI: 1.028-20.936), and the risk of renal dysfunction increased in people with hypertension+ diabetes or with the coexistence of three diseases, compared with people with a single disease( OR=16.441, 95% CI: 5.325-50.783; OR=15.985, 95% CI: 4.237-60.312); In the 60-74 age group, hypertension alone also significantly increased the risk of renal dysfunction( OR=3.950, 95% CI: 1.911-8.165). With comorbidities, the most significant influence was the coexistence of three diseases( OR=6.245, 95% CI: 2.521-15.468), followed by hypertension+ obesity( OR=5.640, 95% CI: 2.550-12.476)and hypertension+ diabetes( OR=4.330, 95% CI: 1.990-9.421); In ≥75 age group, chronic diseases and comorbidities were associated with a high risk of renal dysfunction, with obesity alone and hypertension obesity posing the highest risk( OR=6.746, 95% CI: 2.193-20.757; OR=6.570, 95% CI: 3.178-13.582), followed by the coexistence of three diseases( OR=4.749, 95% CI: 2.110-10.687). Conclusions:The prevalence of hypertension, diabetes, and obesity varies with aging.The effect of chronic diseases on the risk of chronic kidney disease with reduced renal function in the elderly population is different from that in the non-elderly population.