OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

Triggering receptor expressed on myeloid cells 2 （TREM2） is expressed in resident non-parenchymal cells （NPCs） and is involved in various pathological processes including liver inflammation and immunoregulation. In recent years， TREM2 has attracted attention in the field of acute and chronic liver diseases， and more and more studies have shown that TREM2 is a potential target for the treatment of acute and chronic liver diseases； however， there is a lack of systematic summary for the mechanism of action of TREM2 in acute and chronic liver diseases. Therefore， this article reviews the latest research advances in the regulatory role of TREM2 in acute and chronic liver diseases， in order to provide new ideas for the clinical prevention and treatment of acute and chronic liver diseases.

Autoimmune hepatitis （AIH） is an autoimmune disease characterized by liver parenchymal destruction and chronic fibrosis， and it is often mediated by T cells. The pathogenesis of AIH involves multiple factors， including sex， region， environmental factors， and genetic susceptibility. A notable predisposition is observed in female individuals， and the incidence rate of AIH in female individuals is significantly higher than that in male individuals. This sex difference is associated with various factors， and sex hormones may be an important cause of the female predominance of AIH， although the specific mechanisms remain unclear. An in-depth understanding of the mechanism of action of sex hormones in the pathogenesis of AIH will help to better understand the pathogenesis of the disease and may provide important clues for developing future treatment methods and prevention strategies. This article reviews the mechanism of action of estrogen and androgen in regulating the pathogenesis of AIH by regulating T cells， in order to provide new ideas and directions for further exploring the potential role of sex hormones in the etiology of autoimmune diseases.

OBJECTIVE To develop a pharmaceutical service model for discharge medication order review and medication education （hereinafter referred to as the “proactive pharmaceutical service model”）， and evaluate its effects. METHODS The data of discharged patients were collected retrospectively from Rheumatology and Immunology Department of our hospital during January to June 2023 and January to June 2024. Patients discharged from January to June 2024 were classified as the intervention group （489 cases）， while patients discharged from January to June 2023 were classified as the control group （535 cases） based on the different pharmaceutical service models they received. The control group received traditional service model， and the intervention group additionally got proactive pharmaceutical service model based on the control group. The primary outcome measures [the number of discharge medications， the number of medication errors， and the occurrence of adverse drug-drug interaction （DDI）] and follow-up outcome measures （the adjustment of medication regimen due to intolerance， unplanned hospital admissions， and proactive seeking of pharmaceutical services after discharge） were compared between the two groups. The discharge medication order review status， the occurrence of adverse DDI in patients with polypharmacy， and bedside medication education status for patients receiving the proactive pharmaceutical service model were all recorded. RESULTS From January to June 2024， a total of 1 052 discharge medication order review for inpatients were reviewed， and 174 instances of medication errors were identified. Polypharmacy was observed in 579 patients， with an incidence rate of 55.04%. The incidence of adverse DDI was significantly higher in patients with polypharmacy compared to those without polypharmacy （P＜0.001）. Pharmacists completed medication guidance for 394 instances of high-risk patients prone to the incidence rate of medication errors at home. The number of discharge medications， the incidence rate of medication errors， instances of medication not matching the diagnosis， dosage and administration errors， adverse DDI， and the incidence rate of patients who required adjustment of medication regimen due to intolerance were all significantly lower in the intervention group compared to the control group （P＜0.05）. Additionally， the incidence rate of patients who proactive seeking of pharmaceutical services after discharge was significantly higher in the intervention group compared to the control group （P＜0.05）. However， there was no significant difference in the incidence rate of unplanned hospital admissions between the two groups （P＞0.05）. CONCLUSIONS The established proactive pharmaceutical service model can reduce medication errors， enhance patient recognition of pharmaceutical services， and ensure medication safety for discharged patients at home.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

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Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.

Metabolic associated fatty liver disease （MAFLD） has become one of the most prevalent chronic liver disease worldwide， and its progression to liver fibrosis is a key influencing factor for prognosis and the risk of complications. In recent years， novel drugs， such as selective thyroid hormone receptor-β agonists， glucagon-like peptide-1 receptor agonists， and fibroblast growth factor 21 analogs， have shown preliminary efficacy in the treatment of MAFLD-related liver fibrosis； however， such drugs have limited overall effectiveness， and there is still a lack of ideal therapeutic strategy to address the disease across its different stages. Traditional Chinese medicine （TCM）， with its characteristics of multiple targets and systemic regulation， has shown unique advantages in this field. This article systematically reviews the basic and clinical research on the anti-fibrotic mechanisms of compound TCM prescriptions and their active components in recent years， focusing on the key processes including hepatic stellate cell activation， lipid metabolism disorders， oxidative stress， immune inflammation， and gut-liver axis dysfunction. Meanwhile， it is pointed out that there are still certain issues in current research， including ambiguities in the clarification of mechanisms， a lack of standardized evaluation systems， and the need to improve the quality of clinical evidence. Future research should emphasize the standardization and quality control of TCM herbal preparations and integrate emerging technologies， such as omics analysis， organoid models， and real-world data， to advance TCM intervention of MAFLD-related liver fibrosis toward well-defined mechanisms， clear therapeutic pathways， and robust scientific evidence. TCM is expected to play a vital role in the multi-dimensional targeted intervention and stage-specific management of MAFLD-related liver fibrosis， in order to provide new perspectives and comprehensive solutions for the precise treatment of chronic liver diseases.

In vitro,platelets are readily activated,which complicates the process of quality control.In con-trast,nanoparticles possess distinct advantages due to their small size,high surface area ratio,biocompatibili-ty,and modifiability.These properties enable them to inhibit platelet aggregation through encapsulation or multi-modification,thereby ensuring the stability of quality control products for clinical platelet assays.This paper delineates the properties of the two existent forms of platelet-nanoparticle complexes,their synthesis principles,and their applications in the medical field.The text goes on to examine the preparation methods of some platelet-nanoparticle complexes and their applications in the fields of cancer therapy,wound healing,and immune disorders.It also explores the potential relationship between platelet-nanoparticle complexes and exo-some-nanoparticle complexes.Additionally,the future research directions of nanoparticles in platelet plasmino-genics are discussed in this paper,emphasizing the effects of nanoparticle concentration,size,and surface modi-fication on platelet aggregation.This provides a theoretical basis for the development of stable and controllable platelet plasminogenics.

Objective:Constructing efficacy evaluation index of TCM in treating kidney-yang deficiency syndrome based on three-dimensional hybrid method.Methods:The outcome index list of kidney-yang deficiency syndrome was preliminarily constructed through literature research, questionnaire survey and expert interview. The core indicators of kidney-yang deficiency syndrome were screened by Delphi questionnaire, and the expert consensus meeting was held to determine the core outcome of kidney-yang deficiency syndrome.Results:The TCM symptoms of kidney-yang deficiency syndrome: 7 items: frequent urination at night, waist pain, low libido, chills, fatigue, diarrhea and mental malaise. Related core indicators of kidney-yang deficiency syndrome: Level quality of life score (scale), sex life level (sexual self satisfaction, sexual life log, etc.)two entries, objective indicators in the core index and stronger correlation disease, curative effect evaluation, can be combined with clinical research involves the related diseases, used to supplement the curative effect, as recommendations, not as the main body of kidney-yang deficiency syndrome curative effect evaluation content.Conclusion:This study refers to the clinical trial of the TCM core outcome to develop technical specifications, in the development process and methods, through the "combination of qualitative and quantitative research methods" "combination of subjective and objective indicators" "combination of doctor-patient evaluation" three dimensions of mixed research methods, formation of kidney-yang deficiency syndrome curative effect evaluation of the core outcome, for the kidney-yang deficiency syndrome curative effect evaluation standard of prophase research foundation, to provide ideas and methods for the evaluation of curative effect of syndrome.