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 analyze the effect of a high salt diet on ovarian mitochondrial function.Methods Twenty female ICR mice were randomly divided into a normal salt diet(NSD)group and a high salt diet(HSD)group(n = 10 each).The NSD group was given a normal salt diet and the HSD group was given an 8%NaCl diet for 4 weeks.A high salt-treated cell model was established by inducing COV-434 cells cultured in vitro with NaCl.Western blotting was used to detect the protein expression of superoxide dismutase(SOD)and ComplexesⅠ-Ⅴ.The activity of SOD and succinate dehydrogenase(SDH)was detected kinetically.A chemiluminescence assay was used to detect adenosine triphosphate(ATP)levels.Results Compared with the NSD,the HSD significantly reduced the expression level of ComplexⅠin ovarian mitochondria(P＜0.01),significantly increased the expression level of ComplexⅤ(P＜0.05),and significantly reduced the activity of SDH and content of ATP(P＜0.01).The expression level of ComplexesⅠandⅡdecreased significantly(P＜0.05),expression level of ComplexⅤ increased significantly(P＜0.05),activity of SDH decreased significantly(P＜0.01),and content of ATP was insufficient(P＜0.01)in COV-434 cells cultured under high salt conditions.Conclusion High salt can lead to mitochondrial dys-function in the mouse ovary,such as imbalanced oxidative homeostasis,changed expression level of electron transport chain complexes,blocked tricarboxylic acid cycle,and insufficient ATP level.

Objective The critical genes associated with exhausted CD8+T cells were screened and validated by mapping the single-cell transcriptome profile of high-grade serous ovarian cancer(HGSOC).Methods The specific subtypes of T cells in the tumor microenvironment were analyzed using the single-cell sequencing data from the early stage of laboratory(SRA database:PRJNA756768)and integrating 5 HGSOC sequencing from the database,and the differentiation trajectory of T cell subsets was ex-plored through pseudotime analysis.Differential gene enrichment was used to determine immunosuppressed CD8+IL-2Low and CD8+IFN-γLow T cell subsets and differential genes,and candidate molecules closely related to exhausted CD8+T cells were screened based on patient prognosis.Flow cytometry was used to analyze the expression of PHLDA1 on CD8+T cells,CD4+T cells and Treg cells dur-ing the activation to exhaustion process of T cells in human PBMCs.ELISA was used to detect the levels of IFN-γ and IL-2 secreted by CD8+T cells in PHLDA1High and PHLDA1Low.Finally,flow cytometry was used to analyze the association between PHLDA1 and ex-hausted markers PD-1 and TIM-3.Results The results showed that T cells were grouped in three ways:(1)IL-2High and IL-2Low;(2)IFN-γHigh and IFN-γLow;and(3)exhausted and cytotoxic CD8+T cells.Subsequently,the intersection of its differentially expressed genes was taken,and the key gene PHLDA1 was ultimately screened.Flow cytometry analysis suggested that during the process of T cell activation to exhaustion,the expression of PHLDA1 continued to increase on CD8+T cells,CD4+T cells and Treg cells;The ELISA results showed that the levels of IFN-γ and IL-2 secreted by CD8+PHLDA1High T cells were significantly lower than those of CD8+PHLDA1Low T cells.Meanwhile,the CD8+PHLDA1High T cell subset could simultaneously cover the exhausted T cell types of CD8+TIM-3+and CD8+PD-1+.Conclusion Based on single-cell sequencing data,this study identified PHLDA1 as a key molecule responsi-ble for CD8+T cell exhaustion in OC,providing new insights for immunotherapy of OC.

Objective:To compare the efficacy and safety between WangShiBaoChiWan and mosapride in the treatment of functional dyspepsia (FD).Methods:From September 2019 to September 2020, patients with postprandial fullness and early satiation who met the Rome Ⅳ criteria for FD diagnosis were enrolled from 15 hospitals, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical College. The subjects were randomly divided into WangShiBaoChiWan (experimental) group and mosapride (control) group in the ratio of 1∶1. The treatment regimens were WangShiBaoChiWan+ mosapride simulator, WangShiBaoChiWan simulator+ mosapride, respectively with a treatment period of 2 weeks. The primary efficacy outcome was the improvement rates of main symptoms before and after treatment, the secondary efficacy primary efficacy outcome was the total clinical effective rate and the change of the single symptom score. And the safety indicator included adverse events. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:A total of 251 FD patients were enrolled in the full analysis set, including 124 in the experimental group and 127 in the control group; 241 FD patients were in the per-protocol analysis set, including 117 in the experimental group and 124 in the control group. The analysis of per-protocol analysis set showed that the improvement rates of the main symptoms of the experimental group and the control group were (66±29)% and (60±30)%, respectively, and the difference was not statistically significant ( P>0.05). The improvement rate of the main symptoms of the experimental group reached 117% of that of the control group, which exceeded the expected non-inferiority standard of 80%. The total clinical effective rates of the experimental group and the control group were 76.07% (89/117) and 75.81% (94/124), respectively, and the difference was not statistically significant ( P>0.05). The results of full analysis set showed that the incidence of adverse events of the experimental group and the control group was 1.62% (2/124) and 1.57% (2/127), respectively, and the difference was not statistically significant ( P>0.05). There were no serious adverse events in the two groups. Conclusion:The improvement rate of the main symptoms of WangShiBaoChiWan is not inferior to that of mosapride in the treatment of FD, and it has good safety.

Anti- N-methyl- D-aspartic acid (NMDA) receptor encephalitis is an autoimmune encephalitis mediated by anti-NMDA receptor antibody. At present, the diagnosis of the disease depends mainly on typical clinical symptoms and detection of specific antibodies in cerebrospinal fluid. Early and timely treatment can curb the disease progression and improve the prognosis of the disease. However, because of the atypical clinical manifestations of patients and long waiting time for antibody detection, early identification is difficult. Imaging equipment is more popular in primary hospitals in China, and it is easier to perform imaging examination for suspected patients in the early stage; therefore, this article aims to review the imaging characteristics and current imaging research progress of anti-NMDA receptor encephalitis in recent years, so as to improve clinicians' understanding and early recognition of this disease.

The current treatments of metastatic malignant melanoma include chemotherapy,targeted therapy,immune therapy and radiation therapy,but the treatment outcome is far from optimism.In order to im-prove the treatment efficiency,it is urgent to improve early diagnosis,and develop more effective treatment drugs and delivery systems.The application of nanotechnology in the diagnosis and therapy of melanoma can re-duce the resistance to the drugs,increase efficacy and reduce side effects.

Objective To evaluate effects of acitretin on HaCaT cells cultured in hypoxic condition,and to preliminarily explore the possible therapeutic mechanisms of acitretin in psoriasis.Methods HaCaT cells were divided into several groups to be cultured in hypoxic condition with the presence of acitretin at concentrations of 10-5,10-6,10-7 and 10 8 mol/L respectively,with cells treated with dimethyl sulfoxide (DMSO) as DMSO control group and those receiving no treatment as blank control group.Cellular proliferative activity was evaluated by CCK-8 assay after 12-,24-and 36-hour hypoxic culture in vitro.The mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were determined by reverse transcription (RT)-PCR and Western-blot analysis,respectively,after 24-hour hypoxic culture.Results After 24-hour hypoxic culture,the cellular proliferation rate was inhibited by 13.31％ ± 1.15％,21.86％ ± 5.31％,32.05％ ± 2.99％ and 37.28％ ± 3.21％ in the 10 8-,10-7-,10-6-and 10-5-mol/L acitretin groups respectively.With the increase of culture duration and acitretin concentrations,the degree of inhibition on cellular proliferation increased gradually.Compared with the blank control group,the 10-5-mol/L acitretin group showed significantly decreased protein expression of HIF-1α (0.319 ± 0.180 vs.1.196 ± 0.088,P ＜0.05),as well as decreased mRNA and protein expressions of VEGF (mRNA:0.442 ± 0.090 vs.1.108 ± 0.073;protein:0.216 ± 0.066 vs.1.174 ± 0.186;both P ＜ 0.05).However,no significant difference was found in the mRNA expression of HIF-lα between the 10-5-mol/L acitretin group and blank control group.Conclusion Acitretin can suppress the in vitro proliferation of HaCaT cells cultured in hypoxic condition,and down-regulate the expressions of HIF-1α and VEGF proteins as well as VEGF mRNA.

Objective To evaluate the application value with Energy Spectrum CT multi -parameter quanti-tative value in differentiating pulmonary occupying lesions (>0.5cm in diameter).Methods Those were retrospec-tively analyzed on 58 cases in pulmonary occupying lesions performed spectrum dual -phase enhanced CT scan and confirmed by pathology,including malignant group 48 cases;10 cases of benign group.Iodine content(IC)was meas-ured in arterial phase(AP)and venous phase (VP)in iodine based on the image and the level of the aorta,and nor-malized iodine concentrations were calculated in the two phases lesions compared with aorta,and the difference between the two normalized iodine concentrations ICD (ICD =NICvp -NICap).To measure the CT value of lesions on 50keV and 100keV energy image,and calculate the energy attenuation curve slope,namely |Hu (100 kev -50kev)/Hu50 |.The differences of NIC,curve slope,and ICD were compared between benign and malignant pulmonary occupying lesions using independent sample t test method.Results In two phase scan,NIC,curve slope of the venous phase and ICD in malignant group were significantly higher than the benign group,(NIC,curve slope of the venous phase and ICD of the malignant group:NICap:0.180 ±0.051,NICvp:0.463 ±0.086,1.696 ±0.475,ICD:0.284 ± 0.071;NIC,curve slope of the venous phase and ICD of the benign group:NICap:0.123 ±0.062,NICvp:0.290 ± 0.119,1.169 ±0.582,ICD:0.166 ±0.073,),but there was no significant difference between the patients with benign and malignant lesions in curve slope of the arterial phase.Conclusion Energy spectrum CT dual -phase enhanced scan can differentiate the nature of benign and malignant pulmonary occupying lesions,and has certain clinical application value.

ObjectiveTo evaluate the effect of high-frequency jec ventilation and bilevel positive airway pressure (BiPAP) ventilation in the severe dyspnea caused by central airway stenosis and explore the deferent application of two ventilation models.MethodsA retrospective analysis was designed to collect the serious dyspnea patients caused by central airway stenosis from January 2006 to January 2009.The patients were divided into group H and group B according to the different ventilation models,and the effect of relieving dyspnea and ameliorating hypoxemia was compared.ResultsSeven cases were in group H,and 9 cases were in group B.The therapeutic effect of relieving dyspnea was 14.29 ％(1/7) in group H.There were only 4 cases accepting high-frequency jec ventilation and the effect of relieving dyspnea was 25.00％(1/4).Two cases failed in high-frequency jec ventilation treatment and succeeded in BiPAP treatment thereafter,and 1 case failed in BiPAP treatment initially but was treated effectively by high-frequency jec ventilation after dyspnea relapsed.In group B,there were only 6 cases accepting BiPAP ventilation and the effect ofrelieving dyspnea was 83.33％ (5/6),and after adding the cases who accepting the sequential therapy of high-frequency jec ventilation and BiPAP ventilation the effect rate was 88.89％ (8/9).The difference had statistical significance(P =0.006).In ameliorating hypoxemia,the effect rate of group H was 100.00％ (7/7),of group B was 88.89％(8/9),and the difference had no statistical significance (P =0.563 ).Conclusions The high-frequency je ventilation is effective to relieve hypoxemia but is short of relieving dyspnea and subjective symptom,and it is suit for life support preoperative and intraoperative.The BiPAP ventilation is effective to relieve dyspnea and subjective symptom and hypoxemia,so the treatment effect is better than high-frequency jec ventilation,and it is suit in relieving symptom temporarily,pre-operative preparation and malignant tumor palliative treatment.

BACKGROUND: Breast augmentation with polyacrylamide hydrogel injection has been used nearly for a decade in some Chinese medical therapy units. More patients need to be removing injections or a second augmentation due to complications. More attention should be paid for possibility of complications concomitant with breast malignant tumor. OBJECTIVE: Two cases of breast invasive duct carcinoma diagnosed after removing injection were analyzed retrospectively in order to increase the importance of detection rate of breast malignant tumor. METHODS: Two cases in all 41 assembled patients which were removed polyacrylamide hydrogel injections from 82 breasts were diagnosed with invasive carcinoma. The characteristics of medical history, physical diagnosis, image diagnosis and pathological examination were analyzed retrospectively. RESULTS AND CONCLUSION: The detection rate of breast malignant tumor should arise more attention in patients requiring removal of polyacrylamide hydrogel injection. The following aspects should be emphasized such as the comprehensive analysis for the results of physical diagnosis and image diagnosis, tumor-free operation with more samples from suspicious nodules and frozen pathological examination. The principles of cancer surgery should be followed in pathological diagnosed cases in case of iatrogenic metastasis and spread of breast malignant tumor.