ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

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

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

In the context of"Artificial Intelligence(AI)+Education"era,this study introduces the teaching reform and devel-opment path of the course"Fundamentals of Immunology and Pathogenic Biology"by Professor Lu Fangguo's team at Hunan University of Traditional Chinese Medicine.After twenty years of exploration,the course has successfully transitioned from traditional teaching to intelligent teaching,achieving a comprehensive upgrade in educational concepts,teaching methods,and resources.The reform process is divided into three stages:Early exploration,comprehensive reform,and deepening development.It encompasses the construction of a smart teaching platform,the development and promotion of new forms of digital teaching resources,and the deep integration of ideological and political education.This reform has significantly enhanced teaching quality and students'overall competencies,showcasing the innovative spirit of educators.It has gained nationwide recognition and promotion,providing valuable references for the innovation of medical education in the new era.

In the context of"Artificial Intelligence(AI)+Education"era,this study introduces the teaching reform and devel-opment path of the course"Fundamentals of Immunology and Pathogenic Biology"by Professor Lu Fangguo's team at Hunan University of Traditional Chinese Medicine.After twenty years of exploration,the course has successfully transitioned from traditional teaching to intelligent teaching,achieving a comprehensive upgrade in educational concepts,teaching methods,and resources.The reform process is divided into three stages:Early exploration,comprehensive reform,and deepening development.It encompasses the construction of a smart teaching platform,the development and promotion of new forms of digital teaching resources,and the deep integration of ideological and political education.This reform has significantly enhanced teaching quality and students'overall competencies,showcasing the innovative spirit of educators.It has gained nationwide recognition and promotion,providing valuable references for the innovation of medical education in the new era.

Objective To investigate the effects of intraoperative intravenous administration of dexmedetomidine(DEX)on the recovery quality of donors undergoing pure laparoscopic donor hepatectomy.Methods A total of 56 liver donors who were going to undergo scheduled pure laparoscopic donor hepatectomy were enrolled and randomly assigned to two groups,a DEX group(n=28)and a control group(n=28).Donors in the DEX group received DEX infusion at a dose of 1 μg/kg over 15 minutes through a continuous pump,which was followed by DEX at 0.4 μg/(kg·h)until the disconnection of the portal branch.Donors in the control group were given an equal volume of 0.9% normal saline at the same infusion rate and over the same period of time as those of the dex infusion in the DEX group.The primary outcome was the incidence of emergence agitation(EA).The Aono's Four-point Scale(AFPS)score was used to assess EA.The secondary observation indicators included intraoperative anesthesia and surgery conditions,spontaneous respiration recovery time,recovery time,extubation time,scores for the Ramsay Sedation Scale,the incidence of chills,numeric rating scale(NRS)score for pain,and blood pressure and heart rate after extubation.Results The incidence of EA was 10.7% and 39.3% in the DEX group and the control group,respectively,and the incidence of EA was significantly lower in the DEX group than that in the control group(P=0.014).The APFS scores after extubation in the DEX group were lower than those in the control group(1[1,1]vs.2[1,3],P=0.005).Compared to the control group,the dosages of intraoperative propofol and remifentanil were significantly reduced in the DEX group(P<0.05).During the recovery period,the number of donors requiring additional boluses of analgesia,the blood pressure,and the heart rate were all lower in the DEX group than those in the control group(P<0.05).No significant differences between the two groups were observed in the spontaneous respiration recovery time,recovery time,extubation time,the incidence of chills,NRS score,scores for the Ramsay Sedation Scale,and the length-of-stay in postanesthesia care unit(PACU)(P>0.05).Conclusion DEX can reduce the incidence of EA after pure laparoscopic donor hepatectomy and improve the quality of recovery without prolonging postoperative recovery time or extubation time.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective : To investigate the expression of class A scavenger receptor 1(MSR1) in the lungs of silico⁃ sis mice and its role in inflammation and lipid metabolism mediated by mouse mononuclear macrophages (RAW264. 7) . Methods : 24 C57BL/6 male mice were randomly divided into control group , exposed 7 d group , exposed 14 d group , exposed 28 d group , with 6 mice in each group. RAW264. 7 cells were divided into control group , siRNA⁃MSR1 group , SiO2 group and siRNA⁃MSR1 + SiO2 stimulation group. The pathological changes of lung tissue in mice were observed by HE and VG staining. Lipid accumulation was observed under oil red O staining microscope. Immunohistochemical staining (IHC) was used to detect the expression and localization of MSR1 . The expression of MSR1 , tumor necrosis factor (TNF) Ⅳα , interleukin (IL) Ⅳ6 and IL⁃1β were detected by Western blot. Results : Compared with the control group , HE and VG staining results showed that inflammatory cells gathered and collagen distribution increased in the lung tissue of silicosis mice. Oil red O staining showed that a large number of orange⁃red lipid droplets appeared in the lung tissue of mice. IHC results showed that the expression of MSR1 was up⁃regulated in silicosis inflammation stage. Western blot results showed that the expression of MSR1, TNF⁃α , IL⁃6 and IL⁃1β was up⁃regulated in silicosis inflammation stage (P < 0. 05) . The expression of MSR1 in the SiO2 cell stimulation group was up⁃regulated ( P < 0. 05 ) , and the expression of MSR1 in the siRNA⁃MSR1 group decreased (P < 0. 05) , and lipid droplets also appeared in the SiO2 cell stimulation group. The accumulation of lipid droplets in siRNA⁃MSR1 + SiO2 stimulation group was lower than that in SiO2 group (P < 0. 01) . ELISA results showed that the expression of TNF⁃α , IL⁃6 and IL⁃1β in SiO2 cell stimulation group was up⁃regulated ( P <0. 05) . Compared with SiO2 group , the expression of TNF⁃α , IL⁃6 and IL⁃1β in siRNA⁃MSR1 + SiO2 stimulation group was down⁃regulated (P < 0. 05) . Conclusion MSR1 is involved in the regulation of lipid components and the release of inflammatory factors in lung tissue and cells of silicosis mice. Inhibition of MSR1 expression can an⁃ tagonize the inflammatory response and abnormal lipid accumulation in macrophages. MSR1 may be a potential therapeutic target for future intervention in the progression of silicosis.

Objective : To explore the regulatory role of microRNA⁃455 ⁃3p ( miR⁃455 ⁃3p) in lymphangiogenesis of rat silicosis model , and to investigate the effect of miR⁃455 ⁃3p targeted regulation of vascular endothelial growth factor C (VEGF⁃C) on the tubular structure formation of human lymphatic endothelial cells ( HLECs) . Methods: The rats were randomly divided into the silicosis model group and the normal control group. The silicosis model group were injected with silicon dioxide (SiO2 )dust suspension , and the control group was injected with the same amount of normal saline. HE , Masson and immunohistochemistry staining were used to observe the pathological changes and lymphangiogenesis of lung tissue. The expression levels of miR⁃455 ⁃3p and VEGF⁃C in lung tissues of rats were detected by Quantitative real⁃time PCR ( RT⁃qPCR) and Western blot; The miR⁃455 ⁃3p inhibitors and negative controls ( NC) were transfected into HLECs , and the expression levels of miR⁃455 ⁃3p and VEGF⁃C in cells were detected by RT⁃qPCR and Western blot. The migration ability of HLECs was detected by scratch test , the ability of tubular structure formation was detected by matrigel tube formation test , and dual luciferase experiments were used to verify the targeting relationship between miR⁃455 ⁃3p and VEGF⁃C. Results : Compared with the normal control group , in the silicosis model group , a large number of inflammatory cells gathered and collagen gradually deposited in the pulmonary interstitium , and there was lymphatic hyperplasia in the lung. The expression of miR⁃455 ⁃3p in the lung tissue was lower than that in the control group , and the expression of VEGF⁃C was higher than that in the control group ; After transfection with HLECs , compared with the NC group , the expression of miR⁃455 ⁃3p in the cells of the Inhibitors group decreased , the expression of VEGF⁃C increased , and the ability of cell migration and tubular structure formation increased(P < 0. 05) ; VEGF⁃C was confirmed as a target gene of miR⁃455 ⁃3p by the dual luciferase experiments. Conclusion miR⁃455 ⁃3p can affect the tubular structure formation ability of HLECs and regulate lymphangiogenesis by targeting the expression of VEGF⁃C.