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 confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

Objective To investigate the protective effect and mechanism of glutathione peroxidase 3-(GPx3)modified mesenchymal stem cells(MSC)against radiation-induced lung injury(RILI).Methods GPx3-modified MSCs were injected into the tail vein of mice whose lungs were irradiated with 20 Gy.Lung tissues were collected and sections were stained to observe pathological changes.The expression levels of inflammation-related factors were detected by real time quantitative PCR(qPCR),while the levels of malondialdehyde(MDA),H2O2,and 8-hydroxyguanine(8-OHG)were detected via biochemical experiments.Additionally,RNA damage was assessed by reverse transcription blocking combining with double primer PCR.Results GPx3-modified MSCs significantly improved the pathological damage in post-radiation lung tissues and inhibited the fibrosis process and inflammatory response.GPx3-modified MSCs were able to scavenge reactive oxygen species(ROS)more effectively,resulting in a reduction of lipid peroxidation products such as MDA and oxidative damage to RNA formation of 8-OHG.Conclusion By decreasing ROS accumulation,GPx3-modified MSCs can potentially reduce oxidative damage and attenuate RILI.GPx3-modified MSCs can improve the therapeutic efficacy against RILI.

OBJECTIVE To optimize the heart-nourishing granule extraction process by network pharmacology and Box-Behnken response surface method. METHODS The active ingredients of heart-nourishing granule were excavated through network pharmacology and their mechanism of action in the treatment of coronary heart disease was preliminarily explored. Molecular docking technology was used to predict the binding ability of the active ingredients to the main targets. At the same time, based on the compatibility relationship between the monarch, minister, assistant and guide of the prescription, the pharmacological effects of the ingredients, and the content determination index components of each medicinal flavor in the 2020 edition of the Chinese Pharmacopoeia, the process evaluation index components of heart-nourishing granule were further determined. In addition, combined with the analytic hierarchy process to determine the weight of each component, the Box-Behnken response surface method was used to optimize the extraction process of heart-nourishing granule. RESULTS The main active components of heart-nourishing granule screened were catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin. By acting on core targets such as AKT1, IL-6, IL-1b, VEGFA, JUN and MAPK3, they regulated lipid and atherosclerosis, MAPK signaling and other pathways played a role in the treatment of coronary heart disease. Molecular docking results showed that the binding energies of active components and core targets predicted by network pharmacology were all < -5.0 kJ·mol-1. Five components catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin were calculated by analytic hierarchy process method. The weight coefficients of arginyl glycosides were 0.329 7, 0.329 7, 0.164 8, 0.109 9, and 0.065 9, respectively. The Box-Behnken response surface method obtained the optimal water extraction process: 10 times the amount of water was used to extract twice, and each time was decocted for 1.5 h. The verification test showed that the contents of the five components were consistent with the predicted values, and the RSD values were all <5%. CONCLUSION The extraction process of heart-nourishing granule based on network pharmacology and Box-Behnken response surface methodology is stable and feasible, which provided an experimental basis for its further quality improvement.

Objective To study the clinical value of whole －body magnetic resonance diffusion weighted imaging(WB－DWI) in evaluating the chemotherapy response for lung cancer,thus to provide evidence for optimizing clinical imaging examination. Methods From October 2017 to May 2018,60 patients with lung cancer confirmed by histopathology in Linfen Central Hospital were selected. The patients underwent DWI examinations before chemotherapy and after two cycles of chemotherapy. The change of tumor size,distant metastasis and apparent diffusion coefficient (ADC) value were compared before and after chemotherapy. The correlation between the change rate of ADC value and the shrinkage rate of tumor size in the effective group was analyzed. Results Of 60 cases,1 case had new cerebral metastases after chemotherapy. There were statistically significant differences in ADC value [(1. 12 ± 0.33) ×10 －3mm2/svs.(1.56±0.40) ×10 －3mm2/s]andtumorsize[(4.63±2.75)cmvs.(2.28±1.45)cm] between before and after chemotherapy in the effective group(t= －3. 954,4. 711,all P＜0. 01). There was correlation between the change of ADC value and tumor size(r=0. 34,P＜0. 05). Conclusion WB－DWI can not only detect the change of tumor size and distant metastasis quickly and effectively,but also can observe the microscopic changes of tumor cells by measuring ADC value. So it can predict the early therapeutic response of the tumor and make effective evaluation for the staging and chemotherapy response of lung cancer.

The pathogenesis of diabetes is complicated by several factors including autoimmunity, environment, heredi?ty, and etc. Autophagy is a kind of intracellular biodegradation processes, which plays an important role in intracellular ho?meostasis of islet cells. In diabetes, autophagy is involved in the endoplasmic reticulum stress, mitochondrial dysfunction and inflammatory, and it affects the development of the disease. In this paper, we reviewed the interactions of autophagy with endoplasmic reticulum stress and mitochondrial dysfunction with inflammation in diabetes in order to investigate the patho?genesis of diabetes, to find new strategies for prevention or treatment of diabetes.

Objective To detect the expression of β-catenin in the tissues of primary central nervous system lymphoma (PCNSL), and to discuss its function in PCNSL.Methods The paraffin embedded tissues from 10 patients diagnosed as PCNSL from October 2010 to April 2012 were collected as the experimental group.The paraffin embedded tissues from 10 patients with lymphadenitis were collected as the control group.Quantitative real-time PCR and immunohistochemical method were used to detect the expression of β-catenin in these tissues, and the relationships between β-catenin and clinical data were analyzed.Results Immunohistochemistry results showed that β-catenin protein was localized in the cytoplasm and (or) nucleus.Among 10 PCNSL patients, β-catenin protein was positive in 4 patients, while it was no positive in all of 10 lymphadenitis patients, with the significant differences between both groups (P ＜ 0.05).The β-catenin gene relative expression level was 4.70±0.57 and 1.00±0.27 in the experimental group and the control group, respectively.β-catenin expression was no correlation to age, PS score, cerebrospinal fluid protein level and serum lactate dehydrogenase level of patients with PCNSL.Conclusions Whether in mRNA level or in protein level, β-catenin expression is always high in PCNSL tissues, and its protein is expressed in the cytoplasm, however, this phenomenon was not observed in the tissue of lymphadenitis.

Objective To evaluate hemodynamic status,pathological,imaging and ultrasound changes of residual lymph nodes from diffuse large B-cell lymphoma (DLBCL) after chemotherapy and their relationship with clinical treatment after chemotherapy.Methods 50 DLBCL patients undergoing full course of chemotherapy but still bearing residual lymph nodes were examined with ultrasound-guided lymph node biopsy.Some examinations were combined with PET-CT to analyze properties of residual lymph nodes.Results 64 lymph nodes were identified by color Doppler ultrasounda in the 50 DLBCL patients treated with full course of chemotherapy.Among them,53 lymph nodes from 42 patients did not show artery blood flow and HE staining of these lymph node biopsy met the clinical standard for complete remission.For the other 11 lymph nodes from 8 patients,ultrasound examination displayed smrounding blood flow inside.At the same time,PET-CT showed that these lymph nodes had higher SUV values,implying high metabolic state in these tissues,which was in agreement with ultrasonic examination results.However,HE staining of these lymph nodes biopsy demonstrated only residual lesion but no tumor tissue.Conclusions Lymph nodes still exist in DLBCL patients treated with full course of chemotherapy.Ultrasound and PET-CT examination have high accuracy in diagnosing benign and malignant residual lymph nodes in follow-up examination on 4 weeks after chemotherapy showed that lymph nodes are over ＞ 1.5 cm in length and have central or peripheral blood flow.Therefore,PET-CT examination of tumor could be considered as a reference index in characterizing residual tumors after chemotherapy.