Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

AIM:To observe the changes of atrial fibrillation susceptibility,and the remodeling of atrial myo-cyte action potential,ultrarapid activation delayed rectifier potassium current(IKur)and transient outward potassium cur-rent(Ito)in elderly mice,and to explore the mechanism of atrial fibrillation from the single cell electrophysiological level.METHODS:The C57BL/6J mice were divided into old group(20 months old)and young group(4 months old).Atrial fi-brillation was induced by esophageal atrial pacing.The atrial myocytes were isolated,and action potential and ion currents were recorded with patch-clamp technique.The associated proteins were detected by Western blot technique.RE-SULTS:(1)Compared with young mice,the total incidence of atrial fibrillation was significantly increased in old mice(20.0%at 4 months old vs 60.0%at 20 months old,P<0.01).(2)The action potential duration of atrial myocytes in aged mice was shortened,and more significantly after stimulation.(3)The density of Ito and IKur in atrial myocytes of aged mice increased significantly,from(12.6±1.4)pA/pF to(21.7±1.1)pA/pF,and from(7.5±1.5)pA/pF to(13.3±2.1)pA/pF,respectively(P<0.01).After stimulation,the current increased more significantly,especially in older atrial cells.Compared with the young mice,the steady-state activation curve of Ito in the atrial myocytes of the aged mice shifted towards the depolarization,suggesting that activation of Ito channels in the aged mice increased at the same voltage stimula-tion.(4)Compared with young group,the expression of KV4.2(generating Ito)and KV1.5(generating IKur)proteins in the atrial tissue of the mice in old group was significantly increased,and the expression of caveolin-3 and end-binding protein 1(EB1)was up-regulated,suggesting that the increases in KV4.2 and KV1.5 total channel proteins and effective proteins in the cell membrane might contribute to the increase in the remodeling of potassium currents in the elderly atrial myo-cytes.CONCLUSION:The incidence of atrial fibrillation in elderly mice is significantly augmented,which may be related to the increases in Ito and IKur in atrial myocytes.The remodeling of potassium currents in elderly atrial myocytes is one of the electrophysiological bases leading to the shortening of action potential duration and the occurrence of atrial fibrillation.

Objective To investigate the predictive performance of serum soluble CD40 ligand(sCD40L),interleukin-17(IL-17)and neutrophil extracellular traps(NETs)in combination for intracranial aneurysm rupture.Methods A total of 120 patients with intracranial aneurysms admitted from January 2022 to January 2025 were selected and divided into low-risk group and medium-high-risk group according to different rupture risks.After propensity score matching with 1:1 ratio and caliper matching(caliper=0.02),there were 60 patients in each group.The general data and serum levels of sCD40 L,IL-17 and NETs were compared between the two groups.Multivariate logistic regression analysis was used to analyze the risk factors of intracranial aneurysm rupture.The linear relationship between serum sCD40 L,IL-17,NETs and the risk of intracranial aneurysm rupture was analyzed by smoothing curve fitting.The receiver operating characteristic(ROC)curve,clinical impact curve(CIC)and clinical decision curve analysis(DCA)were used to evaluate the predictive performance of serum sCD40L,IL-17 and NETs for intracranial aneurysm rupture.Results The irregular shape of aneurysms,the proportion of the longest diameter of aneurysms≥7 mm and the levels of serum sCD40L,IL-17 and NETs in the low-risk group were lower than those in the medium-high-risk group(P<0.01).The shape of aneurysm,the longest diameter of aneurysm,sCD40L,IL-17 and NETs were the independent risk factors for intracranial aneurysm rupture(P<0.05).After adjusting for other covariates,serum sCD40L,IL-17 and NETs were positively correlated with the risk of intracranial aneurysm rupture(P<0.05).The ROC curve showed that the area under the curve of serum sCD40L,IL-17 and NETs in combination for predicting the risk of intracranial aneurysm rupture was the largest.The DCA and CIC showed that both the net benefit of the combined prediction model of serum sCD40L,IL-17 and NETs in predicting the risk of intracranial aneurysm rupture and the coincidence rate with the actual situation were relatively high.Conclusion The elevated levels of serum sCD40L,IL-17,and NETs in patients with intracranial aneurysms are associated with their rupture risk.The combination of the three indicators has a high predictive performance for the risk of intracranial aneurysm rupture.

Depression is a heterogeneous mental disorder in which the interaction between genetic susceptibility and environ-mental factors plays a key role in its pathogenesis.Although the specific mechanisms of the disease still need to be thoroughly studied and elucidated,there is now a broad consensus that epi-genetic markers have a central influence on its mechanism of ac-tion.DNA methylation of brain-derived neurotrophic factor(BD-NF)is not only regarded as a promising epigenetic biomarker of pathology,but may also help predict the efficacy of antidepres-sants.In this paper we reviewed the gene structure of BDNF and its DNA methylation regulation mechanism,and also analyzed the changes of DNA methylation of this factor in depression pa-tients and animal models,aiming to provide new ideas and theo-retical support for clinical research.

BACKGROUND:Exosomes have been confirmed to be closely related to cartilage degeneration in osteoarthritis.However,the role and mechanism of exosome-derived genes in cartilage degeneration of osteoarthritis have not been fully elucidated.OBJECTIVE:Bioinformatics analyses were used to screen the genes related to cartilage degeneration in the synovial exosomes of patients with osteoarthritis,and to determine their biological functions and signaling pathways in order to provide new therapeutic targets for delaying cartilage degeneration in osteoarthritis.METHODS:Firstly,osteoarthritis-related exosome dataset GSE185059 and cartilage degeneration dataset GSE114007 were downloaded from Gene Expression Omnibus(GEO)database to screen exosome-derived cartilage degeneration related genes.GO functional and KEGG pathway enrichment analyses were performed based on the screened exosome-derived cartilage degeneration related genes.Protein-protein interaction network was drawn and Ingenuity Pathway Analysis(IPA)was conducted to screen and obtain key exosome-derived cartilage degeneration-related genes.Finally,qRT-PCR was used to verify the expression of key genes in osteoarthritis cartilage tissue and interleukin-1β stimulated chondrocyte models.RESULTS AND CONCLUSION:(1)There were 831 differentially expressed genes in the GSE185059 dataset and 5 323 differentially expressed genes in the GSE114007 dataset.A total of 94 exosome-derived cartilage degeneration related genes were screened after the intersection of these differentially expressed genes,of which 51 genes were down-regulated and 43 genes were up-regulated.(2)GO functional enrichment analysis showed that the up-regulated genes were mainly involved in the positive regulation of cell-cell adhesion,the positive regulation of T cell activation,and chronic inflammatory response,while the down-regulated genes were mainly involved in biological processes such as cell aggregation,cartilage differentiation and development,and skeletal system morphogenesis.(3)KEGG pathway enrichment analysis showed that exosome-derived cartilage degeneration-related genes were mainly involved in tryptophan enrichment metabolism,vitamin B6 metabolism,and leukocyte transendothelial migration.(4)The constructed protein-protein interaction network confirmed the existence of multiple interaction relationships among exosome-derived cartilage degeneration-related genes.Combined with five algorithms in CytoHubba software,four key exosome-derived cartilage degeneration-related genes were further screened,namely THY1,CYP1A1,NFKB2,and COL6A3.(5)The results of qRT-PCR showed that compared with normal cartilage,the expressions of THY1 and COL6A3 in osteoarthritic cartilage were increased,while the expression of CYP1A1 and NFKB2 was decreased.Similarly,compared with the unstimulated group,the expression of THY1 and COL6A3 in the interleukin-1β induced chondrocytes was upregulated,while the expression of CYP1A1 and NFKB2 was downregulated.(6)These results indicate that THY1,CYP1A1,NFKB2,and COL6A3 are genes related to cartilage degeneration in the exosomes of synovial fluid of patients with osteoarthritis,and may participate in the pathogenesis of osteoarthritis by regulating biological processes such as protein tyrosine kinase activity and lipid metabolism,as well as nuclear factor-κB signaling pathway and focal adhesion signaling pathway.However,the specific regulatory roles and molecular mechanisms of these key genes in cartilage degeneration need to be further verified by experiments.

Precise management of the activity dose is a core component of the(early mobilization,EM)plan for ICU patients.However,the lack of clinical practice guidelines related to EM dose of existing programs hinders the implementation and development of EM in ICU patients to some extent.Therefore,this review focuses on 4 aspects,covering the definition of activity dose,assessment tools,the current clinical implementation status,and implications for future nursing.The aim is to systematically review the assessment tools and intervention strategies for the activity dose of EM in ICU patients,providing a reference for optimization of EM programs.

Objective:To investigate the effect of Jaceosidin on immune escape of colorectal cancer(CRC)cells by regulating cyclic guanosine monophosphate-adenylate synthase(cGAS)-stimulator of interferon gene(STING)signal pathway.Methods:Human CRC cells HCT116 were cultured in vitro and grouped into control group,Jaceosidin-L group(25 μmol/L),Jaceosidin-M group(50 μmol/L),Jaceosidin-H group(100 μmol/L),activator group[100 μmol/L Jaceosidin+10 μmol/L cGAS activator manganese chloride(MnCl2·4H2O)],and inhibitor group(100 μmol/L Jaceosidin+1 μmol/L cGAS inhibitor RU.521);CCK-8 method was applied to de-tect the proliferation of HCT116 cells;flow cytometry was applied to detect apoptosis of HCT116 cells;HCT116 cells were co-cultured with NK cell to detect NK cell killing activity;ELISA was applied to detect the levels of IFN-γ and Granzyme B in the supernatant of co cultured cells;Western blot and qRT-PCR were applied to detect the expression of cGAS-STING signaling pathway and apoptosis related factors.Results:Compared with the control group,the A450 value and Bcl-2 expression of HCT116 cells in the Jaceosidin-L,Ja-ceosidin-M,and Jaceosidin-H groups were obviously reduced,the apoptosis rate,and the expression of cGAS,STING and Bax were obviously increased,and were dose-dependent(P<0.05);compared with the control co culture group,the levels of IFN-γ and Gran-zyme B,and NK cell killing activity in the supernatant of the Jaceosidin-L,Jaceosidin-M,and Jaceosidin-H co culture groups were significantly increased,in a dose-dependent manner(P<0.05);cGAS activator MnCl2·4H2O enhanced the inhibitory effects of high-dose Jaceosidin on HCT116 cell proliferation,immune escape,and the promoting effect on cell apoptosis,cGAS inhibitor RU.521 weakened the inhibitory effects of high-dose Jaceosidin on HCT116 cell proliferation,immune escape,and the promoting effect on cell apoptosis.Conclusion:Jaceosidin inhibits HCT116 cell proliferation,immune escape,and promotes cell apoptosis by activating cGAS-STING signaling pathway.

OBJECTIVE Healthcare-associated infection(HAI)surveillance is a crucial tool for healthcare manage-ment and public health prevention,the World Health Organization(WHO)released simplified technical guidelines of HAI surveillance to enhance the HAI surveillance in areas with limited medical resources.This study explores the applicability and implementation pathways of the WHO's simplified standards for HAI surveillance in China.METHODS This study used text analysis and qualitative interviews to compare the differences of HAI sur-veillance criteria between China and WHO.Interviews were conducted with professionals of infection prevention and control(IPC)to explore the opportunities and challenges of implementing WHO simplified standards in China.RESULTS Twenty-two IPC professionals with long-term experiences participated in the interviews.Main themes derived from the interview were:WHO simplified standards could enhance the sensitivity of HAI surveil-lance,this approach provided insights for a risk early warning surveillance and improved surveillance in primary healthcare institutions.It also increased the international comparability of Chinese HAI surveillance results.How-ever,the implementation of the WHO simplified standards required further pilot validation,higher levels of infor-matic surveillance and clinical diagnostic capabilities.CONCLUSION This study explores the feasibility and accept-ability of the WHO's simplified HAI surveillance in China,provides references for the transformation of China's HAI surveillance models and systems.