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

Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.

Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.

Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

Objective To compare the differences in gut microbiota between cirrhosis patients receiving transjugular intrahepatic portosystemic shunt(TIPS)and those not,and explore the relationship between TIPS surgery and gut microbiota in order to provide new ideas for improving the prognosis of cirrhosis patients after TIPS surgery based on gut microbiota.Methods Those who had received TIPS surgery previously were assigned into the operation group,and those without the surgery served as the control group.Their stool samples were collected for 16S rRNA sequencing,and the correlation between gut microbiota and clinical indicators was analyzed.Results There were no significant differences in gender,age,body mass index(BMI),etiology and other baseline data between the 2 groups(P＞0.05),but obvious differences were observed in clinical serological indicators between them,including INR,APTT,RBC and PT counts,and HGB,ALP,ALB,total bilirubin(TBIL),and URE levels(P＜0.05).No statistical difference in alpha diversity was observed between the operation group and the control group(P＞0.05),but beta diversity was obviously different(P＜0.01),among which Bacteroides was increased in the operation group(P＜0.01)and Bifidobacterium was increased in the control group(P＜0.05).The function prediction analysis of gut microbiota showed that the metabolism of D-glutamine and D-glutamate(P＜0.05)and biosynthesis with secondary bile acids(P＜0.05)were up-regulated in the operation group compared with the control group.Correlation analysis between clinical indicators and flora indicated that TBIL and direct bilirubin(DBIL)were significantly correlated with the metabolic pathways of Bacteroides and Secondary bile acids biosynthesis.Conclusion Characteristic changes in gut microbiota are found in cirrhosis patients with and without TIPS surgery.Bacteroides may be involved in the regulation of metabolism of bile acids and thus increase bilirubin level.