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

ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

Objective:To evaluate the new model of group screening combined with opportunistic screening for the diagnosis and treatment of gastric cancer.Methods:Group screening combined with opportunistic screening was used for gastric cancer screening. (1) Group screening. Cluster sampling was used to screen gastric cancer by endoscopy in high-risk population (aged 40-<70 years) of rural residents in Weihai from July 2017 to December 2020, and biopsy was obtained for histopathology if necessary. Main collection parameters included the detection rate of advanced gastric cancer, early gastric cancer and high-grade intraepithelial neoplasia (HGIN). (2) Opportunistic screening. The changes of the detection rates of early gastric cancer in opportunistic screening in 2 hospitals in Weihai area were observed during the same period of time.Results:(1) In group screening, from July 2017 to December 2020, the first batch of 8 000 cases of gastric cancer screening were completed. The cases of advanced gastric cancer, early gastric cancer and HGIN were 36, 28, and 62, respectively. The detection rates of gastric cancer and early gastric cancer were 0.80% (64/8 000) and 43.75% (28/64), respectively. The proportion of early gastric cancer+HGIN who received endoscopic submucosal dissection (ESD) was 77.78% (70/90), and the rate of curative resection was 100.00%(70/70). (2) Opportunistic screening: from July 2017 to December 2020, the annual early gastric cancer detection rates in opportunistic screening in Wendeng District Traditional Chinese and Western Medicine Hospital were 16.67% (1/6), 20.00% (3/15), 23.53% (4/17), and 33.33% (6/18) in the consecutive 4 years, respectively. The annual detection rates of early gastric cancer in opportunistic screening in Ru Shan Peoples Hospital were 14.74% (14/95), 23.80% (60/252), 25.49% (65/255), and 24.04% (50/208), respectively. The detection rates of opportunistic screening for early gastric cancer in hospitals in Weihai city increased year by year.Conclusion:In areas with high incidence of gastric cancer, a certain scale of group screening can lead to a wider range of opportunistic screening, resulting in the increase of the detection rate of early gastric cancer. The new model of diagnosis and treatment of gastric cancer is worth recommendation.

Objective:To understand the basic situation of vaccination of medical staff engaged in infectious disease related work, analyze the influencing factors of vaccination, and provide reference for the vaccination of occupational population.Methods:A self-designed questionnaire was designed to investigate the staff engaged in infectious disease related work in the disease control and hospital systems of 11 cities in Zhejiang Province. The contents of the questionnaire included the basic information of the medical staff, the vaccination situation after work and its influencing factors and vaccination willingness. A total of 1 446 valid questionnaires were collected. Chi square test and multivariate logistic regression were used to analyze the influencing factors of whether or not they had been vaccinated with work-related vaccine after engaging in infectious disease-related work.Results:Of the respondemts, had been vaccinated with work-related vaccines after engaging in infectious diseases related work, and the vaccines with the highest coverage rate were hepatitis B vaccine, influenza vaccine, measles vaccine, etc. Work organization, position, unit level and working years related to pathogenic microorganism experiment are the influencing factors for medical personnel to vaccinate work-related vaccine after they are engaged in infectious disease related work; 90.04% of the respondents indicated that they would like to be vaccinated.Conclusions:The vaccination rate of work-related vaccine was low after the medical staff began to work on infectious diseases. The main influencing factors of whether the medical staff were vaccinated with work-related vaccine after they were engaged in the work-related vaccine of pathogenic microorganisms were the working organization, position, unit level and working years related to pathogenic microorganism experiment.

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared

Objective:To investigate the coverage rate and the adverse reactions of National Immunization Program vaccines in children with spinal muscular atrophy (SMA).Methods:A cross-sectional retrospective cohort study was carried out from July 2016 to June 2019, 192 children (116 boys and 76 girls) with SMA registered by Capital Institute of Pediatrics and 191 healthy children (115 boys and 76 girls) vaccinated in Chaoyang Olympic Village Community Health Service Center from July 2016 to December 2018 were included. Questionnaire survey was designed to investigate the vaccination coverage rate and associated adverse events. The t-test and χ 2 test were used to compare the difference between SMA patients and healthy children. Results:The coverage rate of age-appropriate immunization in SMA children was 62.0% (119/192) in general, and were 52.2% (12/23), 55.7% (68/122), and 83.0% (39/47) for SMA type 1-3 patients, respectively (χ 2=12.23, P=0.002). The vaccination coverage rates of Bacillus Calmette-Guerin (BCG) vaccine, the 3 rd dose of hepatitis B, the 3 rd dose of polio, the 3 rd dose of diphtheria-pertussis-tetanus, the 1 st dose of meningococcal polysaccharide group A, the 1 st dose of measles or measles and rubella vaccine, the 1 st dose of Japanese encephalitis vaccine, hepatitis A, measles-mumps-rubella, and group A+C meningococcal polysaccharide vaccine were 100.0% (192 cases), 94.3% (181 cases), 81.8% (157 cases), 88.5% (170 cases), 83.9% (161 cases), 76.6% (147 cases), 80.2% (154 cases), 68.2% (131 cases), 69.8% (134 cases), 54.7% (105 cases), respectively. Among the 73 patients who did not have their planned immunization completed, 57 cases (78.1%) gave up the vaccination due to parents′ concern of potential aggravation of their disease, and 16 cases (21.9%) had the plan discontinued by the immunization department because of the disease. Fever, local redness and swelling were the most common side-effects after vaccination both in SMA patients and healthy children (19.8% (38/192) vs. 18.8% (36/191) , χ 2=0.055, P=0.815). The main abnormal reactions of vaccination were rash and neurovascular edema, without significant difference between these two groups (2.6% (5/192) vs. 3.7% (7/191), χ 2=0.355, P=0.551). The coverage rate of Influenza and pneumococcal vaccine in SMA patients were 22.4% (43 cases) and 31.8% (61 cases), respectively. The incidence of pneumonia in the SMA patients decreased from 59.0% (23/39) to 41.0% (16/39) after vaccination. And none of the Influenza vaccinated patients had the flu in the year of vaccination. Conclusions:The coverage rate of National Immunization Program vaccines in the SMA children is low, especially in type 1 SMA patients, which is mainly due to their guardians′ concern of potential adverse events, even though the incidence of adverse reactions is similar in SMA patients and healthy children. Influenza and pneumococcal vaccine can reduce the risk of pneumonia and flu in children with SMA effectively.

As one of the most common pathogens in aquatic animals, Aeromonas hydrophila exhibits a wide range of pathogenicity. Due to factors like unreasonable use of antibiotics and horizontal gene transfer mediated by plasmids, many resistant strains of Aeromonas hydrophila were isolated from ready-to-eat seafood products in retail markets, supermarkets and restaurants. These strains carry many resistance genes. Therefore, it is essential to explore the key control points, and seek for prevention and control strategies so as to effectively alleviate antibiotic resistance. We review here the prevalence of drug resistance of Aeromonas hydrophila in China, and its main infection and resistance mechanisms, and the main means and strategies for reducing and preventing drug resistance. We also address further research directions and focus on drug resistance in Aeromonas hydrophila of the aquatic product.
Aeromonas hydrophila ; drug effects ; Animals ; Anti-Bacterial Agents ; pharmacology ; China ; epidemiology ; Drug Resistance, Bacterial ; Fish Diseases ; epidemiology ; microbiology ; Fisheries ; Fishes ; Gram-Negative Bacterial Infections ; epidemiology ; microbiology ; Research

Objective To develop an intelligent system which is able to offer an optimized emergency treatment recommendation for fast triage automatically.Methods An algorithm and intelligent platform for grading injury were developed based on physiological signal collecting technology, intelligent grading algorithm and integration technology.A comparison between this system and traditional methods was made.Results This intelligent system was able to increase accuracy by 21%and took only 48%of the time taken by traditional methods.There was significant difference between the two groups(P=0.038<0.05).Conclusion The accuracy of the triage is improved by this intelligent system that is less time-consuming.With this device, the injury statement can be identified quickly and the targeted medical treatment can be performed accurately.The efficiency of emergency treatment in case of disaster will thus be dramatically increased.

OBJECTIVE: To recombinant express hepatoma associated gene(HTA) and pre-test the function of HTA to determine the role of HTA in the development of liver cancer. METHODS: HTA338-616 was amplified from HepG2 cells and cloned into the prokaryotic expression vector pET21a(+)-MBP. The proteins MBP and MBP-HTA were induced, purified by His-tag magnetic bead purification kit and identified by Western blot and ELISA. HepG2 cells were stimulated with MBP or MBP-HTA proteins. MTT assay and colony formation assay were employed to examine the proliferation of these cells and the changes of cell cycle distribution were determined by flow cytometry. RESULTS: The prokaryotic expression plasmid pET21a(+)-MBP-HTA was successfully constructed. We got a 52 kD purified purpose protein.The proliferation of HepG2 cells stimulated with MBP-HTA was significantly higher than those stimulated with MBP and negative controls. HepG2 cells stimulated with MBP-HTA showed significant decrease fraction in G1 phase and increase fraction in S phase, and the cell proliferation was enhanced. CONCLUSION HTA protein can significantly promote the proliferation of HepG2 cells, which may be related to the promotion of G1 phase to S phase.
Base Sequence ; Cell Proliferation ; drug effects ; Escherichia coli ; genetics ; metabolism ; Genes, Neoplasm ; physiology ; Genetic Vectors ; Hep G2 Cells ; Humans ; Maltose-Binding Proteins ; biosynthesis ; genetics ; pharmacology ; Molecular Sequence Data ; Neoplasm Proteins ; biosynthesis ; genetics ; pharmacology ; Open Reading Frames ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; pharmacology