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 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.

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 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.

Objective To explore the clinical efficacy of Shenggu Tablets(mainly composed of Pyritum,Sappan Lignum,Dalbergiae Odoriferae Lignum,Notoginseng Radix et Rhizoma,Anemarrhenae Rhizoma,Rehmanniae Radix,Pheretima,and Os Draconis)combined with extension osteotomy using Taylor spatial frame(TSF)in the treatment of open tibial fracture with bone defect.Methods The clinical data of 73 patients with open tibia fracture and bone defect more than four centimeters admitted to Foshan Hospital of Traditional Chinese Medicine from July 2018 to September 2022 were retrospectively analyzed.The patients were divided into the observation group(37 cases)and the control group(36 cases)according to the medication of Shenggu Tablets or not.The control group was treated with extension osteotomy using TSF,and the observation group was treated with Shenggu Tablets combined with extension osteotomy using TSF until the healing of fractures.Six months after the operation,the clinical effect,total effective rate assessed by imaging,fracture healing time,and the incidence of complications in the two groups were compared.Results(1)Six months after the operation,the distinguished rate of clinical efficacy and the total effective rate assessed by imaging in the observation group were all 100.00%(37/37),which were significantly higher than those in the control group[(83.33%(30/36),86.11%(31/36)respectively],and the intergroup comparison showed that the differences were statistically significant(P＜0.05).(2)The fracture healing time of the observation group was(11.47±0.77)months,which was significantly shorter than that of the control group[(14.42±1.40)months],and the difference was statistically significant(P＜0.01).(3)The total incidence of postoperative complications in the patients of the observation group was 13.51%(5/37),which was significantly lower than that in the control group[38.89%(14/36)],with a statistically significant difference(P＜0.05).Conclusion Shenggu Tablets combined with extension osteotomy using TSF exerts certain efficacy in the treatment of open tibial fracture with bone defect by significantly promoting fracture healing,improving bone transport and speeding up osteogenic mineralization,shortening the time of fracture healing,and reducing the time of wearing the TSF.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.