Metabolic associated fatty liver disease （MAFLD） is the main type of chronic liver disease in the world， with an increasingly higher incidence rate and a younger age of onset. At present， the treatment of MAFLD mainly depends on lifestyle intervention and comorbidity management， and there is still a lack of effective drugs for MAFLD itself. As a classic nonsteroidal anti-inflammatory drug of the salicylic acid family， aspirin can intervene in the pathological process of MAFLD by regulating lipid metabolism， relieving insulin resistance， reducing liver inflammation and oxidative stress response， exerting an anti-liver fibrosis effect， and inhibiting hepatocellular carcinoma， and therefore， it has the value of preventing disease onset， delaying disease progression， and reversing disease condition. This article systematically reviews the mechanism of action and safety of aspirin in the treatment of MAFLD， in order to provide more drug treatment options for MAFLD patients.

Informed consent constitutes a fundamental ethical principle in medical practice. With the in-depth integration of generative artificial intelligence （AI） represented by Chat Generative Pre-trained Transformer （ChatGPT） with medicine， it has brought revolutionary development to traditional informed consent while also introducing new ethical challenges. ChatGPT offers features such as improving the readability of informed consent content， enhancing its comprehensiveness and accuracy， and increasing the convenience of obtaining informed consent. However， as the application of ChatGPT in informed consent is still in the exploratory stage， it is imperative to proactively and fully consider the accompanying ethical issues， such as information security， liability determination， transparency， and fairness. This paper conducted an ethical analysis on the challenges faced by generative AI， represented by ChatGPT， in the application of informed consent and proposed countermeasures， such as upholding free and fully informed consent， strengthening the balance of rights and obligations in informed consent， and establishing a transparent and fair supervision mechanism. The aim was to promote the ethically compliant， orderly， and controllable development of generative AI in the field of medical informed consent.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates in China， and advanced HCC is a difficult issue in current treatment. Immune checkpoint inhibitor （ICI）， as an emerging treatment regimen， has shown a certain effect in clinical practice， but there are still problems such as low overall response rate and a high incidence rate of immune-related adverse events （irAEs）. Traditional Chinese medicine exhibits unique advantages in the treatment of advanced HCC. Through a retrospective analysis of related studies in recent years， this article shows that traditional Chinese medicine combined with ICI can control disease progression， prolong survival time， and reduce irAEs in the treatment of advanced HCC through the synergistic effect between multiple components， targets， and pathways. The potential mechanism of this treatment modality may involve various aspects such as the direct inhibition of tumor cells and the regulation of immune system and intestinal flora.

Objective To evaluate the application of evidence-based perioperative patient-controlled analgesia(PCA)management in patients with liver cancer receiving transcatheter arterial chemoembolization(TACE)treatment.Methods By using the application model of clinical evidence-based practice,the review indicators were formulated based on the best evidence.The baseline assessment was conducted,the barrier factors were analyzed,the best clinical decision was made,the implementation steps of PCA management,including training,monitoring,education,etc.were refined,and two rounds of clinical review were carried out.The knowledge-belief-practice level and the implementation of review indicators in 50 medical and nursing staff engaged in PCA management,as well as the changes in pain scores,the incidence of adverse reactions due to PCA management,and the patient's satisfaction in 159 patients after the application of evidence were compared with their corresponding values determined before the application of evidence.Results After implementing the evidence-based practice plan and applying the evidence,at multiple time points the pain scores and the incidences of adverse reactions were decreased significantly(P＜0.05),the patient's satisfaction increased remarkably(P＜0.01),the execution rate of medical and nursing staff for the review indicators were strikingly increased(P＜0.01),and the knowledge-belief-practice level concerning PCA management was prominently improved(P＜0.01).Conclusion The implementation of perioperative PCA management in patients with liver cancer receiving TACE treatment can help to reduce the perioperative pain level,improve the patient discomfort,increase the patient's satisfaction degree,and improve the ability of medical staff in performing PCA management and evidence-based practices.

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

OBJECTIVE To explore the effectiveness, potential mechanism and compatibility characteristics of efficacy groups of Dunhuang medical prescription Daxiefei decoction in preventing and treating pneumonia based on chemical bioinformatics method. METHODS To study the effect of Daxiefei decoction freeze-dried powder solution on the proliferation activity of lung epithelial cells through cell experiments. Daxiefei decoction was divided into three groups: clearing away heat group, resolving phlegm group, and nourishing Yin group according to its efficacy characteristics. The chemical components of Daxiefei decoction were obtained by TCMSP database and literature search, and the targets were predicted in Swiss Target Prediction database. Pneumonia disease targets were obtained by DrugBank, TTD, Genecards and DisGeNET databases. STRING database and Cytoscape were used to construct the intersection target interaction network and "drug-component-target- pathway" network and DAVID database was used for KEGG pathway enrichment analysis. The network was used to analyze the scientific connotation of the compatibility of efficacy groups. Furthermore, molecular docking was used to evaluate the target-compound affinity and molecular dynamics was used to explore the dynamic molecular mechanism. RESULTS Cell experiments showed that Daxiefei decoction can maintain the proliferation of lung epithelial cells, reverse the decrease of mitochondrial activity induced by LPS and reduce apoptosis. Complex network analysis showed that the pathways enriched by the three functional groups contained in Daxiefei decoction were mainly distributed in two modules: inflammation regulation and reducing airway mucus hypersecretion. Each module was connected by a common target gene and had its own focus. The results of molecular docking showed that the components quercetin, baicalein, isorhamnetin etc. might be the effective multi-target components of Daxiefei decoction. SRC, EGFR, PPARA etc. had good affinity with each potential active component, which might be a potential target of Daxiefei decoction for preventing and treating pneumonia. Molecular dynamics simulation showed that the potential active component quercetin formed stable intermolecular interactions with SRC. CONCLUSION This study initially reveal the material basis and molecular mechanism of Daxiefei decoction in the prevention and treatment of pneumonia. It also explores the scientific connotation of Daxiefei decoction in the prevention and treatment of pneumonia with different efficacy groups, and its modern development and clinical application provide chemical bioinformatics basis.

ObjectiveTo observe the effect of the combination of total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium on reversal cholesterol transport （RCT） in hyperlipidemia rats， and to discuss its mechanism. MethodSixty SD rats were randomly divided into control group， high-fat diet group， total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium low （17 mg·kg^-1+40 mg·kg^-1）， middle （34 mg·kg^-1+80 mg·kg^-1）， high dose （68 mg·kg^-1+160 mg·kg^-1） groups and simvastatin （2.1 mg·kg^-1） group， with 10 mice in each group. The Hyperlipidemia model was duplicated by feeding rats with a high-fat diet for 6 weeks. From the 3rd week， except for the control group and the high-fat diet group given distilled water， other groups were given corresponding drugs intragastric treatment for 4 weeks. The changes in blood lipid and liver function of rats were detected by an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to observe the pathological morphological changes and steatosis of rat liver tissue. The contents of total cholesterol （TC） and total bile acid （TBA） in rat liver tissue and feces were determined by a semi-automatic biochemical analyzer. The mRNA and protein expression levels of peroxisome proliferators-activated receptors γ （PPARγ）， liver X receptors α （LXRα）， ATP-binding cassette transporter G1 （ABCG1） and cholesterol 7α-hydroxylase （CYP7A1） in rat liver tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the contents or activities of TC， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， TBA， aspartate aminotransferase （AST）， alanine aminotransferase （ALT） in serum were significantly increased （P<0.01）， and the contents of high-density lipoprotein cholesterol （HDL-C） in the high-fat diet group were significantly decreased （P<0.01）. The hepatocyte was clearly swollen like ballooning degeneration， with a lot of fat vacuoles and red fat droplets. The contents of TC and TBA in liver tissue and feces were significantly increased （P<0.01）， and the mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly decreased （P<0.01）. Compared with the high-fat diet group， the contents or activities of TC， TG， LDL-C， TBA， AST， and ALT in the serum of rats in administered groups were significantly decreased （P<0.01）， while the content of HDL-C was significantly increased （P<0.01）. Hepatocyte swelling was significantly reduced， and the ballooning degeneration， fat vacuoles， and red lipid droplets in liver tissue were significantly decreased. The contents of TC and TBA in liver tissue were significantly decreased （P<0.05， P<0.01）， and the contents of TC and TBA in feces were significantly increased （P<0.05， P<0.01）. The mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly increased （P<0.05， P<0.01）. ConclusionTotal saponin of Astragali Radix-total alkaloids of Nelumbinis Folium has a positive effect on the prevention and treatment of hyperlipidemia rats， and its mechanism may be related to the activation of PPARγ/LXRα/ABCG1 signaling pathway and regulation of RCT.