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

Chemical pollution-induced damage to ecosystem function has been a global challenge.The latest"Kunming-Montreal Global Biodiversity Framework"proposed reducing pollution risks to levels harmless to biodiversity and function,placing higher demands on chemical risk management at the ecosystem level.Conventional ecotoxicity tests have focused on single species,only to neglect genetic diversity protection and simplify species interactions.Here,we proposed using environmental RNA(eRNA)and metatranscriptomic analysis to establish a multi-species,multi-biological level chemical pollution ecological risk assessment approach in exposed communities.We reviewed the current status and trends of eRNA in chemical pollution risk assessment and proposed a strategy for bioeffect testing from molecules to communities based on eRNA,constructing ecological risk assessment models for different protection goals.Finally,we summarized the theoretical and technical challenges facing eRNA-based toxicity testing and outlined the future applications of eRNA in capturing real ecological effects of chemical pollution in the field.

Objective To analyze the daily quality assurance(QA)measurement results of IBA Sphinx Compact device on the Mevion compact pencil beam scanning proton therapy system for evaluating its clinical application value in proton therapy.Methods The daily QA measurement of Mevion S250i proton therapy system was carried out with Sphinx Compact device for 30 consecutive days,and the measurement results were analyzed.Results The average deviation between the positioning laser and the image center was(0.42±0.27)mm in 30 days.All of the proximal and distal depth errors of the high-and low-energy pencil beams were within 0.50 mm.The position deviation of all the spots measured did not exceed 1.00 mm,and the size deviation was less than 7.5%.The deviation between the image center and the beam center was not more than 0.75 mm.The relative deviation of the flatness of the rectangular field was about 0.5%.The deviation of the output dose of the square field was within 1.0%.Conclusion The proton system daily QA measurement items recommended by AAPM TG-224 report can be accurately and rapidly measured with Sphinx Compact device.The device is a practical and efficient daily QA tool with high practical value in clinic.

Objective:To verify and calibrate the CT modeling curves of three CT devices in RayStation proton treatment planning system (TPS).Methods:CT-mass density (CT-MD) curves were established by CT Hounsfield units of different tissue substitute materials obtained by scanning the model with CT equipment. CT-stopping power (CT-SP) curves were established by calculation based on the chemical composition of various human tissues. The equivalent water thickness of tissue substitute modules was calculated with different CT modeling curves in TPS. The actual equivalent water thickness of various modules was measured by a Bragg peak detector, and compared with the calculated values of TPS to verify the accuracy of different CT models.Results:The differences of CT modeling curves were significantly different under different tube voltage scanning protocols. Compared with CT-MD curves, CT-SP curves based on the stoichiometric calibration were more suitable for proton dose calculation. However, the values of stopping power corresponding to high CT values still needed to be optimized, and the calculation error after calibration was less than 3%.Conclusion:The method of verifying and calibrating CT unit curves of proton TPS is described, proving that the CT-SP curves after stoichiometric calculation are more suitable for proton dose calculation.

Objective     To explore the timing and safety of limited-period lung cancer surgery in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods     Clinical data of of patients infected with COVID-19 undergoing lung cancer surgery (an observation group) in the Department of Thoracic Surgery of Guangdong Provincial People's Hospital, the Department of Thoracic Surgery of General Hospital of Southern Theater Command of PLA, and the Department of Cardiothoracic Surgery of the First Affiliated Hospital of Guangdong Pharmaceutical University from December 2022 to January 2023 were retrospectively analyzed and compared with patients who underwent surgery during the same period but were not infected with COVID-19 (a control group), to explore the impact of COVID-19 infection on lung cancer surgery. Results     We finally included 110 patients with 73 patients in the observation group (28 males and 45 females at age of 52.62±12.80 years) and 37 patients in the control group (22 males and 15 females at age of 56.84±11.14 years). The average operation time of the observation group was longer than that of the control group, and the incidence of anhelation was higher than that of the control group (P<0.05). There were no statistcal differences in blood loss, length of hospital stay, moderate or above fever rate, degree of cough and chest pain, or blood routine between the two groups. Conclusion    It is safe and feasible to perform lung cancer surgery early after recovery for COVID-19 patients with lung cancer.

OBJECTIVE To study the cardiotoxicity of ophiopogonin D′(OPD′) for rat H9c2 cardio? myocytes. METHODS H9c2 cells were exposed to OPD′ 0.1, 1, 5, 10, 20, 25 and 50 μmol·L-1 for 24 h. Cell viability was examined by MTS assay, and the morphological changes in H9c2 cells were quanti? fied. The cell nucleus injury was examined by high content immune fluorescence screening and the morphological changes were observed under a fluorescence microscope. After treatment with OPD′ 0.1, 1, 5 and 10 μmol·L- 1 for 24 h, the effect on reactive oxygen species (ROS), mitochondrial mem? brane potential(MMP) and apoptosis was detected by flow cytometry. RESULTS The viability was sig? nificantly reduced following exposure to OPD′ 0.1, 1, 5, 10, 20, 25 and 50 μmol·L- 1 (P<0.05,P<0.01). The IC50 value was 9.9 μmol ·L- 1 and cell shrinkage and apoptosis occurred. The levels of ROS and apoptosis rate of H9c2 cells were significantly increased after exposure to OPD′ 0.1, 1, 5 and 10 μmol·L-1 for 24 h (P<0.05,P<0.01) and MMP markedly declined (P<0.05,P<0.01). CONCLUSION OPD′ has significent cytotoxicity on H9c2 cells. It may be related to inducing apopotsis pathways.

Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established. To study the protective effects of Tan IIA against hydrogen peroxide (H₂O₂) in human umbilical vein endothelial cells (HUVECs), we pretreated cells with or without different concentrations of Tan IIA for 24 h, then exposed the cells to 400 μM H₂O₂ for another 3 h. Therefore, our data strongly suggests that Tan IIA may lead to increased regeneration of glutathione (GSH) from the glutathione disulfide (GSSG) produced during the GSH peroxidase-catalyzed decomposition of H₂O₂ in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against H₂O₂-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by H₂O₂ via PXR activation. In conclusion, Tan IIA protected HUVECs against H₂O₂-induced cell injury through PXR-dependent mechanisms.
Apoptosis ; Asian Continental Ancestry Group ; Atherosclerosis ; Endothelial Cells* ; Glutathione ; Glutathione Disulfide ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogen Peroxide ; Inflammation ; Oxidative Stress ; Regeneration ; Rhizome ; Salvia miltiorrhiza ; Triacetoneamine-N-Oxyl ; Xenobiotics

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations (−μM) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells.
Apoptosis* ; Blotting, Western ; Cardiotoxicity ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 CYP1A2 ; Cytochromes c ; Doxorubicin ; Myocytes, Cardiac ; Real-Time Polymerase Chain Reaction ; Receptors, Aryl Hydrocarbon* ; RNA, Messenger ; RNA, Small Interfering ; Transfection

OBJECTIVE To investigate the hepatotoxicity mechanisms of ethanol extract of Radix Polygoni Multiflori (RPM) and Radix Polygoni Multiflori Praeparata (RPMP) by high-content screen assay.METHODS HepG2 cells were treated with RPM (10,25,50,100,200 and 300 mg·L-1) and RPMP (10,50,100,300,600 and 1200 mg· L-1) for 3-24 h,respectively.The cell viability was detected by a CellTiter-GloTM luminescent cell viability assay kit.Cell count,reactive oxygen species (ROS),mitochondrial membrane potential (MMP),glutathione (GSH),superoxide dismutase 2 (SOD2),activating transcription factor 4 (ATF4),apoptosis,and cell cycles were investigated by high-content screen assay.Besides,SOD2 and ATF4 levels were confirmed by Western blotting.RESULTS RPM 300 mg· L-1 showed nearly 48 ％ reduction in cell viability compared with cell control (P＜0.01),while RPMP had no significant effect at the same concentration.Both RPM and RPMP decreased the level of MMP (P＜0.05) but incresed levels of GSH,ROS,SOD2 and ATF4 significantly (P＜0.05).Besides,RPM 200 mg· L-1 significantly increased the expression of SOD2 (P＜0.05) at 3 h by high-content screen assay,and the enhanced expression of ATF4 was shown at 6 h (P＜0.05).RPMP 300 mg· L-1 markedly increased the expression of ATF4 at 6 h (P＜0.05),while the expression of SOD2 significantly increased at 24 h (P＜0.05).CONCLUSION Both RPM and RPMP have some cytotoxicity,and the cytotoxicity of RPM is stronger than that of RPMP.The hepatotoxicity mechanisms of RPM and RPMP may be related to cell apoptosis caused by long-term oxidative stress and endoplasmic reticulum stress.