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 characteristic volatile organic compounds(VOCs)in exhaled breath and their diagnostic value in mice with early stage radiation injury.Methods The thermal desorption gas chromatography-mass spectrometry(TD-GC/MS)technique was used to analyze VOCs in exhaled breath of irradiated mice by 60Coγ-ray with 800 cGy.The characteristic VOCs in the early stage of radiation injury were identified,and a diagnostic model was established.Results The 30-day survival rate of mice was 4.2%.There were significant differences in characteristic VOCs at 7 hours after radiation injury,and thirty characteristic VOCs related to early-stage radiation injury were identified.The diagnostic value of differential metabolites in mice after irradiation was evaluated via the ROC curve,and the area under the ROC curve(AUC)of a single compound exceeded 0.8.The diagnostic model was constructed by screening 9 potential biomarkers of exhalation through Fisher discriminant analysis,and its sensitivity and specificity were close to 100%.Conclusion Analysis of VOCs in exhaled breath is expected to provide a non-invasive diagnostic method for early screening and diagnosis of radiation injury.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

[摘 要] 目的：探究miR-323a-3p、四次穿膜蛋白超家族成员1（TM4SF1）在NSCLC组织和细胞中的表达及两者间的靶向调控关系，观察两者表达对A549细胞增殖、迁移、侵袭和裸鼠移植瘤生长的影响。方法：收集2014年1月至12月间青海省人民医院手术切除的20例NSCLC组织及其相应的癌旁组织，qPCR和WB法检测癌组织中miR-323a-3p、TM4SF1 mRNA 和TM4SF1蛋白的表达。向A549细胞转染miR-323a-3p mimic，采用MTT法、Transwell法、WB法检测miR-323a-3p过表达对细胞的增殖、迁移和侵袭以及TM4SF1、细胞周期蛋白D1（cyclin D1）、p21、MMP-2、MMP-9蛋白表达的影响。采用生物信息学预测工具StarBase和双荧光素酶报告基因实验分析miR-323a-3p与TM4SF1靶向关系。将si-TM4SF1转染至A549细胞，以及分别将miR-323a-3p mimic与pcDNA或pcDNA-TM4SF1共转染A549细胞，评估细胞增殖、迁移和侵袭能力的变化；同时建立各组细胞的BALB/c裸鼠移植瘤模型，在14、21和28 d时测量并计算移植瘤体积。结果：与癌旁组织相比，NSCLC组织中miR-323a-3p表达水平明显下调，TM4SF1 mRNA和蛋白表达水平显著上调（均P<0.01）。miR-323a-3p过表达或抑制TM4SF1表达都会降低A549 细胞的增殖、迁移、侵袭能力及cyclin D1、MMP-2、MMP-9蛋白表达而促进p21蛋白表达，并且抑制A549细胞裸鼠移植瘤的生长（均P<0.01）。生物信息学StarBase工具预测和双荧光素酶基因报告实验结果显示miR-323a-3p能够靶向结合TM4SF1基因并调控 TM4SF1的表达。上调TM4SF1表达后，miR-323a-3p过表达对A549细胞恶性生物学行为及cyclin D1、MMP-2、MMP-9蛋白表达、移植瘤生长的抑制作用均被部分逆转（均P<0.01），对p21蛋白表达的促进作用也被逆转（P<0.01）。结论：miR-323a-3p 通过靶向下调肺癌A549细胞中TM4SF1的表达抑制细胞的增殖、迁移、侵袭和裸鼠移植瘤生长。

【Objective】 To evaluate the performance of absorption and elution test and real time PCR in identifying ABO blood group. 【Methods】 The blood samples with weakened antibody expression serologically were screened and analyzed by absorption and elution test, real time PCR and gene sequencing. The gene sequencing results were used as the gold standard to assess the consistency of the other two methods, and the sensitivity and specificity were compared. 【Results】 Compared with the sequencing results (gold standard), absorption and elution test showed moderate consistency, while real time PCR showed good consistency. Both the sensitivity and specificity of absorption and elution test and real time PCR were statistically different. 【Conclusion】 There was a good agreement between real time PCR and gene sequencing in identifying suspicious ABO blood group with weakened antibody expression serologically. Real time PCR, with a low misjudgment rate, has strong ability to detect weak antigen and is more conducive to identify blood type compared with absorption and elution test.

OBJECTIVE： To investigate the best compatibility proportion of Mongolian medicine “Terminalia chebula decomposing the poison of Aconitum kusnezoffii”. METHODS： Totally 40 rats were randomly divided into blank control group （0.05％ CMC-Na）， raw A. kusnezoffii group （0.12 g/kg by crude drug） and raw A. kusnezoffii-T. chebula  （1 ∶ 3，1 ∶ 1，3 ∶ 1， mass ratio） group （0.12 g/kg raw A. kusnezoffii by raw material）， 8 rats in each group. They were given relevant medicine intragastrically once a day， for consecutive 28 d. 0.5 h after last medication， serum contents of cTn-I and MB were determined， and the changes of cardiological structure were observed； the detoxification effects of T. chebula on cardiotoxicity induced by A. kusnezoffii were investigated. Binding rates of 3 kinds of aconitine （concentrations of aconitine， mesaconitine and hypaconitine were 5， 10， 20， 40， 80， 160， 400 ng/mL） to binding rate of plasma protein with normal human plasma were determined by equilibrium dialysis combined with liquid chromtography-mass spectrometry. The concentrations of 3 kinds of aconitine were fixed as 100 ng/mL. After adding main detoxification component tannic acid in different proportions of T. chebula （1 ∶ 0.025， 1 ∶ 0.075， 1 ∶ 0.1， 1 ∶ 0.5）， the effects of them on plasma protein binding rate of 3 kinds of aconitine were investigated； the possible mechanism  of T. chebula decomposing the poison of A. kusnezoffii inducing cardiotoxicity were investigated. RESULTS： In detoxification experiment， compared with blank control group， serum contents of cTn-I and MB were increased significantly in raw A. kusnezoffii group （P＜0.05）. There were obvious pathological changes in myocardial tissue， such as disorder of cell arrangement， cell shrinkage and cytoplasm staining. Compared with raw A. kusnezoffii group， serum contents of cTn-I and MB in raw A. kusnezoffii-T. chebula （1 ∶ 3， 1 ∶ 1， 3 ∶ 1） groups were decreased significantly （P＜0.05）， and there was no significant difference between the raw A. kusnezoffii-T. chebula （3 ∶ 1， 1 ∶ 1） groups and blank control group （P＞0.05）； myocardial pathological changes were improved to varying degrees. The structure of myocardial tissue in raw A. kusnezoffii-T. chebula （3 ∶ 1） groups were similar to blank control group. In the mechanism investigation experiment under the condition of different concentrations， plasma protein binding rates of 3 kinds of aconitine with normal human plasma were about 30％， without statistical significance （P＞0.05） and significant concentration-dependent manner. After adding tannic acid， plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii was decreased to different extent； when 3 kinds of aconitine were combined with tannic acid in the ratio of 1 ∶ 0.1， 1 ∶ 0.075 and 1 ∶ 0.5， the plasma protein binding rate decreased significantly （P＜0.05）， in proportion-dependent manner. CONCLUSIONS： Compatible use of raw A. kusnezoffii-T. chebula （3 ∶ 1） show that best detoxification effect on A. kusnezoffii-induced cardiotoxicity. Under this compatibility ratio， the plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii with normal human plasma is relatively high and the free drug concentration is relatively low.

Objective To establish a quick and accurate method for detection of tree shrew adenovirus(TAV) using TaqMan real-time fluorescence quantitative PCR. Methods Based on the published TAV genome sequence, a 3' conserved sequence was used to design specific probe primers. A standard curve was prepared using a recombinant plasmid containing the target gene fragment. A real-time fluorescence quantitative PCR method was established for detecting TAV based on TaqMan probe. Results The detection method was specific and was not cross-reactive with other common pathogens. The detection limit of the method was 3.7 copies/μL,showing a high sensitivity. The correlation coefficient was 0.998, and the efficiency was 95.7%. The amplification result showed a fine linear relationship,and the repeatability test effect was good. Conclusions The TAV real-time quantitative PCR detection method based on TaqMan probe has been successfully established. It has high sensitivity and reproducibility and can be applied to early detection of TAV infection.

The dried root of Ranunculaceae Aconitum perennial herb of North Aconitum, is commonly used. It has the function of cardiac stimulation, anti-inflammatory and analgesic, anti-tumor and immune regulation. However, its toxicity lower the safety and applicaiton. The pharmacological and toxicological effects were discussed in this paper, in order to provide reference for the intoxication diagnosis and clinical safety.

Objective To investigated the effects of intermittent hypoxia on neuronal apoptosis and autophagy in hippocampus.Methods 30 Wistar rats were randomly divided into normal control group (NC),intermittent normoxia group (IN) and intermittent hypoxia group (IH).The spatial learning and memory function of the rat was assessed using Morris water maze test.The apoptotic cells and the ultrastructure of neurons in the hippocampus tissue were observed by TUNEL and transmission electron microscope,respectively.And the expression of autophagy marker protein LC3 and Beclin-1 were measured by Western blotting.Results The escape latency was significantly longer in IH than in NC and IN group.And the ratio of time spent in the target quadrant was lower in the IH group than in NC and IN group (P＜0.05).The apoptotic rate of rat hippocampal neurons (F =6.01,P=0.037),the amount of double-layer membrane structure-complicating autophagic vacuoles with karyopyknosis,and protein expression level of LC3 and Beclin-1 were significantly higher (all P ＜0.05) in intermittent hypoxia group than in IN and NC group.Conclusions Intermittent hypoxiainduced autophagy and apoptosis in rat hippocampus are significantly increased,which might be one of the possible mechanisms for cognitive dysfunction caused by intermittent hypoxia.