OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

Animal model research on spleen and stomach diseases in traditional Chinese medicine （TCM） is of great significance for elucidating the nature of diseases and syndromes and for revealing the mechanisms of action of Chinese herbal medicinals. At present， studies on classical TCM syndrome models of spleen and stomach diseases mainly focus on spleen deficiency syndrome， liver constraint syndrome， and damp-heat syndrome. Model construction is mostly based on the etiological and pathophysiological characteristics of syndrome， and model evaluation primarily involves macroscopic manifestations and physicochemical indicators. This paper summarizes the current research status of animal models integrating disease and syndrome for seven common spleen and stomach diseases， including chronic gastritis and gastric precancerous lesions， gastroesophageal reflux disease， functional dyspepsia， inflammatory bowel disease， irritable bowel syndrome， functional constipation， and functional diarrhea. The modeling methods and characteristics of disease-syndrome combined animal models for each disease are analyzed. It is proposed that future research on disease-syndrome integration in spleen and stomach diseases should move toward syste-matic， precise， and integrative development， and that interdisciplinary and cross-disciplinary research approaches should be adopted to enhance the predictive value and application efficiency of disease-syndrome combined animal models.

Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM_2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM_2.5 (IQR=64.9 μg·m⁻³) at prior 18 h and NO (IQR=40.5 μg·m⁻³) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.

ObjectiveTo investigate the expression of family with sequence similarity 162 member A （Fam162a）， a mitochondrial inner membrane protein， in the fibrosis of cardiac fibroblasts and its regulatory role in modulating the fibrotic phenotype of cardiac fibroblasts. MethodsFam162a protein expression was detected in myocardial samples from patients with heart failure （HF） and mice with transverse aortic constriction （TAC）-induced myocardial remodeling. Primary neonatal mouse cardiac fibroblasts （mCFs） were isolated and cultured， and a cell model of angiotensin Ⅱ （Ang Ⅱ）-induced myocardial fibrosis was established to determine Fam162a protein expression. Recombinant adenovirus was used to mediate Fam162a overexpression， while small interfering RNA （si-RNA） was employed for Fam162a knockdown. Western blot was performed to detect the expression of fibrosis-related proteins， including COL1A1， COL3A1， and α-SMA. EdU staining assay was used to evaluate cell proliferation capacity， and scratch assay combined with Transwell assay was conducted to assess cell migration ability. Immunofluorescence assay was applied to measure mitochondrial membrane potential for reflecting mitochondrial dysfunction； reactive oxygen species （ROS） detection was performed to evaluate cellular oxidative stress status； MitoSox assay was used to reflect the degree of mitochondrial oxidative damage； and ATP detection was conducted to assess the overall cellular energy metabolism. ResultsFam162a expression was significantly downregulated in the myocardium of HF patients and TAC mice， and Ang Ⅱ-treated mCFs， accompanied by increased expression of COL1A1， COL3A1， and α-SMA （all P＜0.05）. Adenovirus-mediated overexpression of Fam162a significantly inhibited Ang Ⅱ-induced upregulation of fibrosis-related genes， as well as cell proliferation and migration. Accordingly， silencing Fam162a aggravated the fibrotic phenotypes of mCFs treated with Ang II. Further studies revealed that the inhibitory effect of Fam162a overexpression on Ang Ⅱ-induced fibrotic phenotype was suppressed following the addition of rotenone （a mitochondrial oxidative respiratory chain inhibitor）， which was accompanied by mitochondrial membrane potential depolarization， excessive ROS production， and insufficient ATP generation. ConclusionFam162a exerts its inhibitory effect on the fibrotic phenotype of cardiac fibroblasts by maintaining mitochondrial membrane potential， promoting ATP production， reducing reactive oxygen species （ROS） generation， and suppressing Smad3 signaling activation.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To investigate the efficacy and mechanism of Jiedu Bushen Huoxue Prescription in intervening bone and joint damage associated with hepatolenticular degeneration(HLD)by investigating its effect on improving HLD-related bone and joint damage symptoms and on bone metabolism indicators.Methods From March 2022 to August 2022,a total of 57 patients diagnosed with HLD-related bone and joint damage admitted to the First Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine were selected as the study subjects.The patients were randomly divided into an observation group(29 cases)and a control group(28 cases)using a random number table.The control group was given conventional decopper therapy combined with Alfacalcidol Soft Capsules and Alendronate Sodium Tablets,while the observation group was given additional treatment with Jiedu Bushen Huoxue Prescription based on the control group's regimen.The treatment course lasted 8 weeks.Before and after treatment,changes in the Oswestry Disability Index(ODI)score,Numerical Rating Scale(NRS)pain score,and bone mineral density(BMD)values in the two groups were observed to evaluate overall efficacy.Additionally,serum levels of interleukin 1β(IL-1β),interleukin 6(IL-6),C-terminal telopeptide of type I collagen(β-CTX),and 1,25-dihydroxyvitamin D3[1,25-(OH)2D3]in the two groups were measured before and after treatment to observe the impact on bone metabolism indicators.Results(1)After treatment,the ODI scores and NRS pain scores in both groups were significantly decreased compared to those before treatment(P＜0.05),and the decrease in the observation group was more obvious than that in the control group(P＜0.05).(2)After treatment,the BMD values of the bilateral femoral neck and lumbar vertebrae 2-4(L2-L4)in both groups were significantly increased compared to those before treatment(P＜0.05),and the increase in the observation group was more obvious than that in the control group(P＜0.05).(3)After treatment,the serum levels of IL-1β,IL-6,and β-CTX in both groups were significantly decreased(P＜0.05),while the serum levels of 1,25-(OH)2D3 were significantly increased(P＜0.05)compared to those before treatment.The decrease in IL-1β,IL-6,and β-CTX levels and the increase in 1,25-(OH)2D3 levels in the observation group were superior to those in the control group(P＜0.05).Conclusion Jiedu Bushen Huoxue Prescription has certain effect on improving the symptoms of the patients with HLD-related bone and joint damage,and it is effective on significantly alleviating bone and joint pain and improving BMD and joint function.Its mechanism may be related to the improvement of relevant bone metabolism indicators.

Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

AIM To study the chemical constituents from the buds of Aralia chinensis L.var.nuda Nakai and their in vitro anti-inflammatory activities.METHODS The 70％ethanol extract from the buds of A.chinensis var.nuda was isolated and purified by silica gel,Sephadex LH-20,ODS and semi-preparative HPLC,then the structures of compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as 4-(2,2-dibutoxyethyl)phenol(1),trans-linalool-3,7-oxide-6-O-β-D-glucopyranoside(2),2'-O-(9Z,12Z,15Z-octadecatrienoyl)glyceryl β-D-galactopyranoside(3),quercetin-3-O-β-D-glucopyranoside(3'→ O-3''')quercetin-3-O-β-D-galactopyranoside(4),syringaresinol-4'-O-β-D-glucopyranoside(5),p-hydroxybenzaldehyde(6),7α-hydroxystigmasterol 3-O-β-D-glucopyranoside(7),trans-p-hydroxy cinnamic acid methyl ester(8),funingensin A(9),3,4-dihydroxy-acetophenone(10),N-acetyltyramine(11),3,4-di-O-caffeoyl quinic acid(12),chlorogenic acid(13),aralia cerebroside(14),caffeic acid methyl ester(15),tetradecanoic acid(16).The IC50values of compounds 8,10,12 and 13 were(22.19±1.59),(35.25±1.30),(13.38±0.72),(15.73±1.16)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,2-13 are isolated from genus Aralia for the first time.Compounds 8,10,12,13 exhibit significant in vitro anti-inflammatory activities.

Objective To investigate the status of management of iodinated contrast media(ICM)extravasation in Henan Province,as well as nurses' knowledge and influencing factors,in order to provide a basis for optimizing management strategies.Methods A self-designed questionnaire was applied,employing convenience sampling,to survey nursing administrators and nurses in the radiology departments of 55 tertiary hospitals across 16 regions of Henan Province,from December 2024 to January 2025.Multiple linear regression analysis was conducted to explore the factors influencing nurses' knowledge.Results A total of 55 nursing administrators and 64 nurses participated,with a valid questionnaire response rate of 100％.The survey results reveal that only 5.45％of radiology depart-ments utilized high-pressure central venous catheters,and 32.73％employed vascular visualization techniques.When setting the high-pressure injection speed for ICM,only 54.55％of radiology departments required an assessment of the type and model of intravenous access.Additionally,only 9.09％of radiology departments mandated an observa-tion for 2 to 4 hours following ICM extravasation.Furthermore,only 50.91％of radiology departments had estab-lished an information system for ICM use.The nurses' knowledge score regarding the prevention and management of ICM extravasation was(90.00±17.59),influenced by years of experience in radiology and professional titles(P＜0.05).Conclusion The prevention and management measures for ICM in radiology departments in Henan Province need further improvement.Nursing administrators should optimize management strategies,improve relevant training systems,and continuously enhance nurses' knowledge and practical abilities.