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 understand the symptoms of diarrhea of residents in Tianjin and their willingness to vaccinate, to provide reference for health education, prevention and control of infectious diarrhea.Methods:Cross-sectional study design was adopted. From September to December 2023, a questionnaire survey was conducted among some residents as subjects in Nankai District, Beichen District, Baodi District and Binhai Area of Tianjin by multistage stratified cluster random sampling,to collect information such as sociodemographic characteristics, diarrhea symptoms and vaccination intention. According to the formula n=[ u2απ (1 - π)]/ δ2, the estimated sample size was 3 458 cases. The logistic regression model was used to analyze the factors related to the willingness of the respondents to receive diarrhea vaccination. The software SPSS 24.0 was used for statistical analysis. Results:A total of 3 808 subjects were investigated, with the male-to-female ratio as 1∶1.11 (1 806∶2 002), the age was (42.48±21.59) years old, and the education level of middle school or below accounted for 50.84% (1 936/3 808). The incidence rate of diarrhea was 18.28% (696/3 808), and 48.84% (1 860/3 808) were willing to be vaccinated with diarrhea vaccine. The results of multivariate logistic regression analysis showed that the age was 15-59 years old and ≥60 years old (a OR=2.31, 95% CI:1.80-2.96; a OR=1.66, 95% CI:1.38-2.00), lived in Binhai Area (a OR=2.09, 95% CI:1.62-2.71), and those who knew that community health service centers can provide the vaccination (a OR=1.61,95% CI:1.34-1.92), those who walked from the address to the community health service center were less than 15 minutes (a OR=1.54, 95% CI:1.28-1.85), those who often travel or on business (a OR=1.36, 95% CI:1.07-1.73), and those who actively obtained health care information related to diarrhea prevention when going abroad (a OR=1.69,95% CI:1.43-1.98) were more willing to be vaccinated against diarrhea. Conclusions:The incidence of diarrhea symptoms of residents was slightly higher in Tianjin, but they were less willing to be vaccinated against diarrhea. People who often go outside and go abroad were more willing to be vaccinated against diarrhea. It is suggested that the popular science propaganda and health education of diarrhea vaccine should be effectively carried out by using network platform in community.

BACKGROUND:Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells,but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE:To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments,and to explore the regulatory role of CCR1 and CXCR4. METHODS:Human bone marrow mesenchymal stem cells were selected as experimental subjects.CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells.Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment,respectively.The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology.Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION:(1)5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells,and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency.(2)To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells,5 and 10 μmol/L quercetin were selected for the subsequent experiments,and ligustrazine was used as the positive control drug,and the experiments were divided into blank control group,5 μmol/L quercetin group,10 μmol/L quercetin group,and 100 μmol/L ligustrazine group.(3)In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment,and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group.(4)The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4.(5)Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA.(6)This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4.

Objective To observe the effects of ice-water swimming on pathological changes in model gouty rats,and investigate the relevant regulatory mechanism of the purinergic P2X7R receptor.Methods Male Sprague Dawley rats were divided into normal(NORM)and experimental groups including gouty control(GC),ice-water swimming(IWS),and Brilliant Blue G(BBG,a P2X7R inhibitor)groups.Rats in the experimental groups were modeled to simulate hyperuricemia and gouty arthritis by inhibiting uric acid metabolism combined with the Coderre method.Rats in the ice-water swimming group were treated with 5 min of endurance swimming in an ice-water mixture at a depth of about 0.5 m for 0 h and 12 h after modeling by the Coderre method,while rats in the BBG group were injected intraperitoneally with BBG solution once after modeling.Ankle swelling index was calculated using a formula.Serum uric acid levels were detected by uricase assay,and serum levels of the inflammatory factors interleukin(IL)-1β,1L-6,and tumor necrosis factor(TNF)-αwere detected by enzyme-linked immunosorbent assay.The pathological status of the ankle joints was examined by hematoxylin and eosin staining.P2X7R and NLRP3 protein expression levels in synovial tissue were detected by Western blot and immunohistochemistry,respectively.Results Serum uric acid levels and the ankle joint swelling index were significantly higher in the experimental groups compared with the normal group(P＜0.05 or P＜0.01),and the synovial tissues showed different degrees of inflammatory infiltration.The ankle swelling index was significantly higher in the ice-water swimming group compared with the gouty control group at 12 h(P＜0.05).Serum IL-1β,IL-6,and TNF-α levels(P＜0.01)and P2X7R and NLRP3 protein levels in synovial tissues were all significantly elevated(P＜0.05).Histopathology showed that the cartilage surface was broken and the synovial tissue showed severe hyperplasia and erosion,accompanied by numerous inflammatory cell aggregates.There were no significant changes in P2X7R or NLRP3 protein expression or pathology in synovial tissues in the BBG group compared with the gouty control group(P＞0.05),but serum IL-1β,IL-6,and TNF-α levels were all significantly suppressed(P＜0.01).Conclusions Cold stimulation and strenuous exercise simulated by ice-water swimming may exacerbate pathological damage in gouty arthritis via a mechanism related to high P2X7R expression in the joints.

Objective To investigate the effect of whey protein supplementation on rehabilitation of stroke-related sarcopenia patients with diabetes mellitus.Methods Forty-seven stroke-related sarcopenia patients with diabetes mellitus admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2021 to September 2023 were selected and divided into observation group(24 cases)and control group(23 cases)according to random number table method.Patients in both groups were given normal diabetic diet,conventional drug therapy and rehabilitation training,and patients in observation group were given whey protein powder orally every day for 4 weeks.The non-hemiplegic hand grip strength,appendicular skeletal muscle mass index(ASMI),modified Barthel index(MBI),Fugl-Meyer assessment(FMA),mini-nutritional assessment short-form(MNA-SF),serum albumin(Alb),C-reactive protein(CRP)were compared between two groups before and after intervention.Results After intervention,the grip strength,ASMI,FMA,MBI of two groups were significantly higher than before ntervention,and CRP level was significantly lower than before intervention(P<0.05).The grip strength,ASMI,FMA,MBI,MNA-SF score and Alb of observation group were significantly higher than those of control group,while CRP was significantly lower than that of control group(P<0.05).ASMI was positively correlated with Alb,MNA-SF score and grip strength(P<0.05),while CRP was negatively correlated with Alb,MNA-SF score and ASMI(P<0.05).Conclusion Supplementation of whey protein can improve the nutritional status,muscle strength and muscle mass of patients with stroke-related sarcopenia complicated with diabetes mellitus,and improve the physical motor function and the ability of daily living.

Objective:To summarize the clinical characteristics of patients with end-stage heart failure who receive heart transplant under extracorporeal membrane oxygenation (ECMO) support.Methods:The clinical data of 12 pediatric patients who received heart transplant with ECMO support in the Seventh Medical Center of Chinese People′s Liberation Army General Hospital and Guangdong Provincial People′s Hospital, from January 2019 to December 2023 was collected. The data included sex, age, weight, diagnosis, pre-ECMO lactate level, left ventricular ejection fraction (LVEF), vasoactive-inotropic score (VIS), and preoperative ECMO running time. Surgical data included cold ischemia time of the donor heart, cardiopulmonary bypass time, intraoperative use of immunosuppressant, postoperative use of ECMO, duration of postoperative ECMO, rate of successful weaning from ECMO, and survival discharge rate. The paired t-test was performed to compare cardiac function indices before and after left ventricular decompression. Results:The 12 patients ranged in age from 1.1 to 15.8 years, and weighted from 8 to 63 kg. Ten children were diagnosed with dilated cardiomyopathy, one with myocardial underdensification, and one with a novel heterozygous mutation of the SCN5A gene causing overlap syndrome complicated by fatal arrhythmia. Before ECMO, the lactate ranged from 0.6 to>15.0 mmol/L, the LVEF from 6.5% to 43%, and VIS from 3 to 108. Four patients underwent left ventricular decompression supported by preoperative ECMO, and their pulse pressure was significantly increased after decompression ((17.8±2.1) vs. (9.8±1.5) mmHg, 1 mmHg=0.133 kPa, t=11.31, P=0.001), while there was no apparent change in LVEF ((26.8±4.4)% vs. (24.9±4.9)%, t=1.75, P=0.178). A total of 7 children received a second run of ECMO after surgery and 3 of them successfully weaned off ECMO and survived to discharge. In the entire cohort, 10 were successfully weaned from ECMO and 8 survived to discharge. Conclusions:For children with end-stage heart failure supported by ECMO, left ventricular decompression can significantly improve pulse pressure. These patients will eventually require heart transplantation.

Objective:To summarize and analyze clinical characteristics and possible pathogenesis of atopic dermatitis (AD) -like lesions after treatment with interleukin-17 (IL-17) antagonists in patients with psoriasis, so as to improve the clinical management of these patients.Methods:Four patients with psoriasis, who developed AD-like lesions after the treatment with IL-17 antagonists, were reported. A comprehensive update-search was carried out to analyze and summarize clinical characteristics of and therapeutic strategies for other related cases reported in Chinese and international literature.Results:Among the 4 patients in this study, 2 were males and 2 were females, with a history of psoriasis ranging from 10 to 35 years; after 5-month to 2-year treatment with secukinumab, they developed pruritic erythema and papules with exudation on the trunk, limbs and/or face. All the 4 patients had a history of atopic diseases and elevated serum total IgE levels and/or eosinophil counts. AD-like lesions were controlled in 3 patients after treatment with systemic cyclosporine, glucocorticoids and/or antihistamines, as well as topical glucocorticoids and/or tacrolimus, and secukinumab continued to be administered simultaneously; 1 discontinued secukinumab due to repeated AD-like lesions. Totally, 12 articles in English containing 48 patients were included, and a total of 52 patients including the 4 patients in this study were analyzed. Among them, there were 30 males and 22 females, with the age being 50.1 ± 13.6 years; 37 cases were induced by secukinumab, 14 induced by ixekizumab, and 1 induced by brodalumab; the time from the initiation of biologic therapy to the onset of AD-like lesions ranged from 1 week to 2 years; the lesions manifested as pruritic erythema and papules, accompanied by scales or exudation; the skin lesions were mainly distributed on the limbs (41 cases, 78.8%), followed by the trunk (32 cases, 61.5%) and face (20 cases, 38.5%) ; a personal or family history of atopic diseases was reported in 57.7% patients; peripheral blood eosinophil counts increased in 5 cases, and serum total IgE levels were elevated in 17. Thirty-two (61.5%) patients discontinued IL-17 antagonists, and received single or combination therapies, including systemic treatment with cyclosporine, methotrexate, glucocorticoids, antihistamines, other biologic agents and small-molecule drugs, topical treatment with glucocorticoids and/or tacrolimus, and phototherapy; 20 (38.5%) patients continued the previous treatment with IL-17 antagonists, and additionally received topical treatment with or without oral antihistamines or cyclosporine; after the above treatment, the psoriatic and AD-like lesions were controlled in most patients.Conclusions:AD-like lesions after IL-17 antagonist therapy were not common in patients with psoriasis, and these patients developing AD-like lesions were more likely to have a personal or family history of atopic diseases and elevated levels of serum total IgE; based on the disease condition, the treatment with IL-17 antagonists may be considered to continue during the symptomatic treatment of AD-like lesions.

Humans ; Asthma/drug therapy* ; Biological Therapy